Trial Outcomes & Findings for Trastuzumab Deruxtecan (T-DXd) Alone or in Sequence With THP, Versus Standard Treatment (ddAC-THP), in HER2-positive Early Breast Cancer (NCT NCT05113251)

Last Updated: 2026-08-11

Results Overview

Proportion of participants who have no evidence by Hematoxylin \& Eosin (H\&E) staining of residual invasive disease in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0) by central evaluation following completion of neoadjuvant therapy.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

927 participants

Primary outcome timeframe

Through to definitive surgery or discontinuation/withdrawal from study, up to a maximum of approximately 40 months from randomization to primary pCR DCO (12MAR2025)

Results posted on

2026-08-11

Participant Flow

The study is active, not recruiting and conducted in 18 countries worldwide across 147 centres, with 927 patients who were randomized up until 24th April 2024. Results are reported for the study at the data cut-off for the primary analysis for pathologic complete response (pCR) on 12th March 2025.

Eligible patients had histologically documented human epidermal growth factor receptor 2 (HER2) - positive early stage breast cancer. Eligible patients were randomized in a 1:1:1 ratio using an interactive response technology (IRT) to receive either Arm A: Trastuzumab deruxtecan (T-DXd), Arm B: Trastuzumab deruxtecan followed by Paclitaxel + trastuzumab + pertuzumab (T-DXd-THP) or Arm C: Doxorubicin + cyclophosphamide followed by Paclitaxel + trastuzumab + pertuzumab (ddAC-THP).

Participant milestones

Participant milestones
Measure	Arm A Trastuzumab deruxtecan (5.4 mg/kg Q3W for 8 cycles)	Arm B Trastuzumab deruxtecan (5.4 mg/kg Q3W) for 4 cycles, followed by Paclitaxel (80 mg/m2 QW on Days 1, 8, and 15) + trastuzumab (6 mg/kg Q3W on Day 1) + pertuzumab (840 mg loading dose followed by 420 mg Q3W on Day 1) for 4 cycles	Arm C Doxorubicin (60 mg/m2 Q2W) and cyclophosphamide (600 mg/m2 Q2W) for 4 cycles, followed by Paclitaxel (80 mg/m2 QW on Days 1, 8, and 15) + trastuzumab (8 mg/kg loading dose followed by 6 mg/kg Q3W on Day 1) + pertuzumab (840 mg loading dose followed by 420 mg Q3W on Day 1) for 4 cycles
Overall Study STARTED	286	321	320
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	286	321	320

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A Trastuzumab deruxtecan (5.4 mg/kg Q3W for 8 cycles)	Arm B Trastuzumab deruxtecan (5.4 mg/kg Q3W) for 4 cycles, followed by Paclitaxel (80 mg/m2 QW on Days 1, 8, and 15) + trastuzumab (6 mg/kg Q3W on Day 1) + pertuzumab (840 mg loading dose followed by 420 mg Q3W on Day 1) for 4 cycles	Arm C Doxorubicin (60 mg/m2 Q2W) and cyclophosphamide (600 mg/m2 Q2W) for 4 cycles, followed by Paclitaxel (80 mg/m2 QW on Days 1, 8, and 15) + trastuzumab (8 mg/kg loading dose followed by 6 mg/kg Q3W on Day 1) + pertuzumab (840 mg loading dose followed by 420 mg Q3W on Day 1) for 4 cycles
Overall Study Death	8	3	9
Overall Study Withdrawal by Subject	11	4	21
Overall Study As recorded on the Case Report Form (CRF).	1	1	2
Overall Study Ongoing at the time of primary analysis for pCR	266	313	288

Baseline Characteristics

Height was not reported for all subjects.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A n=286 Participants Trastuzumab deruxtecan (5.4 mg/kg Q3W for 8 cycles)	Arm B n=321 Participants Trastuzumab deruxtecan (5.4 mg/kg Q3W) for 4 cycles, followed by Paclitaxel (80 mg/m2 QW on Days 1, 8, and 15) + trastuzumab (6 mg/kg Q3W on Day 1) + pertuzumab (840 mg loading dose followed by 420 mg Q3W on Day 1) for 4 cycles	Arm C n=320 Participants Doxorubicin (60 mg/m2 Q2W) and cyclophosphamide (600 mg/m2 Q2W) for 4 cycles, followed by Paclitaxel (80 mg/m2 QW on Days 1, 8, and 15) + trastuzumab (8 mg/kg loading dose followed by 6 mg/kg Q3W on Day 1) + pertuzumab (840 mg loading dose followed by 420 mg Q3W on Day 1) for 4 cycles	Total n=927 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=286 Participants	0 Participants n=321 Participants	0 Participants n=320 Participants	0 Participants n=927 Participants
Age, Categorical Between 18 and 65 years	252 Participants n=286 Participants	282 Participants n=321 Participants	288 Participants n=320 Participants	822 Participants n=927 Participants
Age, Categorical >=65 years	34 Participants n=286 Participants	39 Participants n=321 Participants	32 Participants n=320 Participants	105 Participants n=927 Participants
Age, Continuous	50.3 Years STANDARD_DEVIATION 11.25 • n=286 Participants	50.0 Years STANDARD_DEVIATION 11.09 • n=321 Participants	50.1 Years STANDARD_DEVIATION 11.32 • n=320 Participants	50.1 Years STANDARD_DEVIATION 11.21 • n=927 Participants
Sex: Female, Male Female	286 Participants n=286 Participants	321 Participants n=321 Participants	320 Participants n=320 Participants	927 Participants n=927 Participants
Sex: Female, Male Male	0 Participants n=286 Participants	0 Participants n=321 Participants	0 Participants n=320 Participants	0 Participants n=927 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	28 Participants n=286 Participants	29 Participants n=321 Participants	28 Participants n=320 Participants	85 Participants n=927 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	257 Participants n=286 Participants	292 Participants n=321 Participants	292 Participants n=320 Participants	841 Participants n=927 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=286 Participants	0 Participants n=321 Participants	0 Participants n=320 Participants	1 Participants n=927 Participants
Race/Ethnicity, Customized Black or African American	7 Participants n=286 Participants	5 Participants n=321 Participants	7 Participants n=320 Participants	19 Participants n=927 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=286 Participants	1 Participants n=321 Participants	1 Participants n=320 Participants	2 Participants n=927 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=286 Participants	2 Participants n=321 Participants	0 Participants n=320 Participants	4 Participants n=927 Participants
Race/Ethnicity, Customized Asian	127 Participants n=286 Participants	160 Participants n=321 Participants	157 Participants n=320 Participants	444 Participants n=927 Participants
Race/Ethnicity, Customized White	139 Participants n=286 Participants	140 Participants n=321 Participants	137 Participants n=320 Participants	416 Participants n=927 Participants
Race/Ethnicity, Customized Other	6 Participants n=286 Participants	9 Participants n=321 Participants	9 Participants n=320 Participants	24 Participants n=927 Participants
Race/Ethnicity, Customized Not reported	5 Participants n=286 Participants	4 Participants n=321 Participants	9 Participants n=320 Participants	18 Participants n=927 Participants
Height	160.248 cm STANDARD_DEVIATION 7.0934 • n=285 Participants • Height was not reported for all subjects.	159.793 cm STANDARD_DEVIATION 6.8713 • n=318 Participants • Height was not reported for all subjects.	160.441 cm STANDARD_DEVIATION 7.1728 • n=320 Participants • Height was not reported for all subjects.	160.158 cm STANDARD_DEVIATION 7.0434 • n=923 Participants • Height was not reported for all subjects.
Weight	66.212 kg STANDARD_DEVIATION 15.2465 • n=286 Participants • Weight was not reported for all participants.	64.879 kg STANDARD_DEVIATION 12.3807 • n=320 Participants • Weight was not reported for all participants.	66.284 kg STANDARD_DEVIATION 14.5867 • n=320 Participants • Weight was not reported for all participants.	65.776 kg STANDARD_DEVIATION 14.0814 • n=926 Participants • Weight was not reported for all participants.
BMI	25.717 kg/m2 STANDARD_DEVIATION 5.3100 • n=285 Participants • BMI was not reported for all participants.	25.383 kg/m2 STANDARD_DEVIATION 4.6143 • n=318 Participants • BMI was not reported for all participants.	25.724 kg/m2 STANDARD_DEVIATION 5.2130 • n=320 Participants • BMI was not reported for all participants.	25.604 kg/m2 STANDARD_DEVIATION 5.0432 • n=923 Participants • BMI was not reported for all participants.
Region of Enrollment China	37 Participants n=286 Participants	43 Participants n=321 Participants	47 Participants n=320 Participants	127 Participants n=927 Participants
Region of Enrollment India	14 Participants n=286 Participants	22 Participants n=321 Participants	20 Participants n=320 Participants	56 Participants n=927 Participants
Region of Enrollment Japan	25 Participants n=286 Participants	21 Participants n=321 Participants	25 Participants n=320 Participants	71 Participants n=927 Participants
Region of Enrollment Korea	17 Participants n=286 Participants	17 Participants n=321 Participants	17 Participants n=320 Participants	51 Participants n=927 Participants
Region of Enrollment Philippines	13 Participants n=286 Participants	17 Participants n=321 Participants	17 Participants n=320 Participants	47 Participants n=927 Participants
Region of Enrollment Taiwan	8 Participants n=286 Participants	20 Participants n=321 Participants	17 Participants n=320 Participants	45 Participants n=927 Participants
Region of Enrollment Thailand	10 Participants n=286 Participants	12 Participants n=321 Participants	9 Participants n=320 Participants	31 Participants n=927 Participants
Region of Enrollment Canada	20 Participants n=286 Participants	19 Participants n=321 Participants	13 Participants n=320 Participants	52 Participants n=927 Participants
Region of Enrollment United States of America	32 Participants n=286 Participants	24 Participants n=321 Participants	28 Participants n=320 Participants	84 Participants n=927 Participants
Region of Enrollment Brazil	11 Participants n=286 Participants	14 Participants n=321 Participants	14 Participants n=320 Participants	39 Participants n=927 Participants
Region of Enrollment Bulgaria	0 Participants n=286 Participants	0 Participants n=321 Participants	0 Participants n=320 Participants	0 Participants n=927 Participants
Region of Enrollment Peru	4 Participants n=286 Participants	5 Participants n=321 Participants	6 Participants n=320 Participants	15 Participants n=927 Participants
Region of Enrollment Poland	20 Participants n=286 Participants	26 Participants n=321 Participants	22 Participants n=320 Participants	68 Participants n=927 Participants
Region of Enrollment Russia	5 Participants n=286 Participants	5 Participants n=321 Participants	2 Participants n=320 Participants	12 Participants n=927 Participants
Region of Enrollment Saudi Arabia	4 Participants n=286 Participants	7 Participants n=321 Participants	6 Participants n=320 Participants	17 Participants n=927 Participants
Region of Enrollment Germany	20 Participants n=286 Participants	16 Participants n=321 Participants	18 Participants n=320 Participants	54 Participants n=927 Participants
Region of Enrollment Italy	31 Participants n=286 Participants	30 Participants n=321 Participants	33 Participants n=320 Participants	94 Participants n=927 Participants
Region of Enrollment Spain	15 Participants n=286 Participants	23 Participants n=321 Participants	26 Participants n=320 Participants	64 Participants n=927 Participants
Hormone receptor status by local assessment and central assessment of HER2- positive status Hormone receptor status: ER and/or PgR positive · HER2-positive status: IHC 3+	185 Participants n=208 Participants • The number analyzed presents the total number of patients within each category.	210 Participants n=236 Participants • The number analyzed presents the total number of patients within each category.	210 Participants n=235 Participants • The number analyzed presents the total number of patients within each category.	605 Participants n=679 Participants • The number analyzed presents the total number of patients within each category.
Hormone receptor status by local assessment and central assessment of HER2- positive status Hormone receptor status: ER and/or PgR positive · HER2-positive status: Other	23 Participants n=208 Participants • The number analyzed presents the total number of patients within each category.	26 Participants n=236 Participants • The number analyzed presents the total number of patients within each category.	25 Participants n=235 Participants • The number analyzed presents the total number of patients within each category.	74 Participants n=679 Participants • The number analyzed presents the total number of patients within each category.
Hormone receptor status by local assessment and central assessment of HER2- positive status Hormone receptor status: ER and PgR negative · HER2-positive status: IHC 3+	72 Participants n=78 Participants • The number analyzed presents the total number of patients within each category.	79 Participants n=85 Participants • The number analyzed presents the total number of patients within each category.	79 Participants n=85 Participants • The number analyzed presents the total number of patients within each category.	230 Participants n=248 Participants • The number analyzed presents the total number of patients within each category.
Hormone receptor status by local assessment and central assessment of HER2- positive status Hormone receptor status: ER and PgR negative · HER2-positive status: Other	6 Participants n=78 Participants • The number analyzed presents the total number of patients within each category.	6 Participants n=85 Participants • The number analyzed presents the total number of patients within each category.	6 Participants n=85 Participants • The number analyzed presents the total number of patients within each category.	18 Participants n=248 Participants • The number analyzed presents the total number of patients within each category.
Hormone receptor status by local assessment and central assessment of HER2- positive status Hormone receptor status: Total · HER2-positive status: IHC 3+	257 Participants n=286 Participants • The number analyzed presents the total number of patients within each category.	289 Participants n=321 Participants • The number analyzed presents the total number of patients within each category.	289 Participants n=320 Participants • The number analyzed presents the total number of patients within each category.	835 Participants n=927 Participants • The number analyzed presents the total number of patients within each category.
Hormone receptor status by local assessment and central assessment of HER2- positive status Hormone receptor status: Total · HER2-positive status: Other	29 Participants n=286 Participants • The number analyzed presents the total number of patients within each category.	32 Participants n=321 Participants • The number analyzed presents the total number of patients within each category.	31 Participants n=320 Participants • The number analyzed presents the total number of patients within each category.	92 Participants n=927 Participants • The number analyzed presents the total number of patients within each category.

PRIMARY outcome

Timeframe: Through to definitive surgery or discontinuation/withdrawal from study, up to a maximum of approximately 40 months from randomization to primary pCR DCO (12MAR2025)

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Arm A n=286 Participants Trastuzumab deruxtecan (5.4 mg/kg Q3W for 8 cycles)	Arm B n=321 Participants Trastuzumab deruxtecan (5.4 mg/kg Q3W) for 4 cycles, followed by Paclitaxel (80 mg/m2 QW on Days 1, 8, and 15) + trastuzumab (6 mg/kg Q3W on Day 1) + pertuzumab (840 mg loading dose followed by 420 mg Q3W on Day 1) for 4 cycles	Arm C n=320 Participants Doxorubicin (60 mg/m2 Q2W) and cyclophosphamide (600 mg/m2 Q2W) for 4 cycles, followed by Paclitaxel (80 mg/m2 QW on Days 1, 8, and 15) + trastuzumab (8 mg/kg loading dose followed by 6 mg/kg Q3W on Day 1) + pertuzumab (840 mg loading dose followed by 420 mg Q3W on Day 1) for 4 cycles
Rate of Pathologic Complete Response (pCR).	43.01 Percentage of participants	67.29 Percentage of participants	56.25 Percentage of participants

SECONDARY outcome

Timeframe: Up to a maximum of approximately 65 months from randomization to EFS final analysis DCO (Apr 2027)

Event-free survival (EFS) is defined as the time from date of randomization until disease progression precluding initial surgery, invasive disease recurrence (local, regional, distant, or contralateral), or death from any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to a maximum of approximately 65 months from randomization to EFS final analysis DCO (Apr 2027)

Outcome measures

Outcome data not reported

Adverse Events

T-DXd

Serious events: 29 serious events

Other events: 269 other events

Deaths: 8 deaths

T-DXd-THP

Serious events: 34 serious events

Other events: 306 other events

Deaths: 3 deaths

ddAC-THP

Serious events: 63 serious events

Other events: 307 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca Clinical Study Information Center

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	T-DXd n=283 participants at risk Description (Arm-group)	T-DXd-THP n=320 participants at risk Description (Arm-group)	ddAC-THP n=312 participants at risk Description (Arm-group)
Cardiac disorders Myocardial infarction	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.32% 1/312 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.71% 2/283 • Number of events 2 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.64% 2/312 • Number of events 2 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.32% 1/312 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.35% 1/283 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	1.2% 4/320 • Number of events 4 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	2.2% 7/312 • Number of events 7 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.32% 1/312 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.71% 2/283 • Number of events 2 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.94% 3/320 • Number of events 3 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/312 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Cardiac disorders Supraventricular tachycardia	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.31% 1/320 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/312 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.32% 1/312 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Vascular disorders Embolism	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.32% 1/312 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Vascular disorders Jugular vein thrombosis	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.64% 2/312 • Number of events 2 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Ear and labyrinth disorders Vertigo positional	0.35% 1/283 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/312 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Vascular disorders Subclavian vein thrombosis	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.32% 1/312 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Endocrine disorders Inappropriate antidiuretic hormone secretion	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.32% 1/312 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Colitis	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.31% 1/320 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/312 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Diarrhoea	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.62% 2/320 • Number of events 2 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.64% 2/312 • Number of events 3 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Blood and lymphatic system disorders Anaemia	0.35% 1/283 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	1.6% 5/312 • Number of events 6 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Diverticular perforation	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.31% 1/320 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/312 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Enterocolitis	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.32% 1/312 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Gastritis	0.35% 1/283 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/312 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Haematochezia	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.31% 1/320 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/312 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Mesenteric artery stenosis	0.35% 1/283 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/312 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Nausea	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.62% 2/320 • Number of events 3 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/312 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Neutropenic colitis	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.31% 1/320 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/312 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.31% 1/320 • Number of events 2 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	2.2% 7/312 • Number of events 7 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Vomiting	0.35% 1/283 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.62% 2/320 • Number of events 3 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.64% 2/312 • Number of events 2 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
General disorders Chest pain	0.35% 1/283 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/312 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
General disorders Chills	0.35% 1/283 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/312 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
General disorders Death	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.31% 1/320 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/312 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
General disorders Pyrexia	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.62% 2/320 • Number of events 2 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	1.3% 4/312 • Number of events 4 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Hepatobiliary disorders Cholelithiasis	0.35% 1/283 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/312 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.32% 1/312 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Immune system disorders Drug hypersensitivity	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.31% 1/320 • Number of events 4 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/312 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Infections and infestations Atypical pneumonia	0.35% 1/283 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.32% 1/312 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Infections and infestations Bacteraemia	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.32% 1/312 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Infections and infestations Bronchitis	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.32% 1/312 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Infections and infestations Covid-19	1.1% 3/283 • Number of events 3 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.94% 3/320 • Number of events 3 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.96% 3/312 • Number of events 3 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Infections and infestations Covid-19 pneumonia	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.31% 1/320 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/312 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Infections and infestations Cellulitis	0.71% 2/283 • Number of events 2 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.31% 1/320 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/312 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Infections and infestations Community acquired infection	0.35% 1/283 • Number of events 1 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/312 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Blood and lymphatic system disorders Myelosuppression	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.00% 0/320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	1.6% 5/312 • Number of events 6 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.

Other adverse events
Measure	T-DXd n=283 participants at risk Description (Arm-group)	T-DXd-THP n=320 participants at risk Description (Arm-group)	ddAC-THP n=312 participants at risk Description (Arm-group)
Respiratory, thoracic and mediastinal disorders Cough	9.2% 26/283 • Number of events 32 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	10.3% 33/320 • Number of events 38 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	14.4% 45/312 • Number of events 49 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.5% 10/283 • Number of events 11 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	6.9% 22/320 • Number of events 22 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	5.1% 16/312 • Number of events 16 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.2% 9/283 • Number of events 19 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	15.3% 49/320 • Number of events 60 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	9.9% 31/312 • Number of events 43 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.2% 12/283 • Number of events 13 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	5.3% 17/320 • Number of events 19 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	5.4% 17/312 • Number of events 20 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Vascular disorders Hot flush	5.3% 15/283 • Number of events 16 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	8.4% 27/320 • Number of events 29 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	7.7% 24/312 • Number of events 28 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Skin and subcutaneous tissue disorders Alopecia	42.4% 120/283 • Number of events 120 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	47.5% 152/320 • Number of events 159 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	49.0% 153/312 • Number of events 163 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Skin and subcutaneous tissue disorders Dry skin	2.8% 8/283 • Number of events 8 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	3.8% 12/320 • Number of events 13 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	9.3% 29/312 • Number of events 32 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Skin and subcutaneous tissue disorders Nail discolouration	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	0.62% 2/320 • Number of events 2 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	5.8% 18/312 • Number of events 18 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Skin and subcutaneous tissue disorders Nail disorder	0.71% 2/283 • Number of events 2 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	2.2% 7/320 • Number of events 7 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	8.0% 25/312 • Number of events 25 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	1.9% 6/320 • Number of events 6 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	5.4% 17/312 • Number of events 17 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Skin and subcutaneous tissue disorders Pruritus	1.1% 3/283 • Number of events 3 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	5.9% 19/320 • Number of events 21 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	3.5% 11/312 • Number of events 12 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Skin and subcutaneous tissue disorders Rash	4.6% 13/283 • Number of events 13 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	14.7% 47/320 • Number of events 59 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	11.9% 37/312 • Number of events 41 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Eye disorders Dry eye	5.3% 15/283 • Number of events 15 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	7.5% 24/320 • Number of events 24 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	5.1% 16/312 • Number of events 20 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Abdominal pain	4.2% 12/283 • Number of events 15 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	5.9% 19/320 • Number of events 21 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	4.8% 15/312 • Number of events 18 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Abdominal pain upper	7.4% 21/283 • Number of events 26 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	8.1% 26/320 • Number of events 29 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	7.4% 23/312 • Number of events 28 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Constipation	33.6% 95/283 • Number of events 132 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	29.1% 93/320 • Number of events 137 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	24.4% 76/312 • Number of events 102 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Diarrhoea	22.6% 64/283 • Number of events 103 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	58.4% 187/320 • Number of events 377 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	53.8% 168/312 • Number of events 277 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Blood and lymphatic system disorders Anaemia	14.8% 42/283 • Number of events 60 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	22.8% 73/320 • Number of events 133 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	48.7% 152/312 • Number of events 238 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Dyspepsia	11.0% 31/283 • Number of events 36 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	8.1% 26/320 • Number of events 35 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	8.0% 25/312 • Number of events 28 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Gastrooesophageal reflux disease	4.9% 14/283 • Number of events 14 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	6.6% 21/320 • Number of events 25 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	7.1% 22/312 • Number of events 27 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Nausea	68.2% 193/283 • Number of events 462 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	64.7% 207/320 • Number of events 435 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	51.6% 161/312 • Number of events 320 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Stomatitis	13.8% 39/283 • Number of events 50 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	18.4% 59/320 • Number of events 69 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	27.6% 86/312 • Number of events 110 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Gastrointestinal disorders Vomiting	30.7% 87/283 • Number of events 168 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	28.4% 91/320 • Number of events 143 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	21.2% 66/312 • Number of events 112 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
General disorders Asthenia	13.4% 38/283 • Number of events 52 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	14.1% 45/320 • Number of events 80 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	22.8% 71/312 • Number of events 103 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
General disorders Fatigue	23.3% 66/283 • Number of events 97 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	23.1% 74/320 • Number of events 110 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	26.3% 82/312 • Number of events 106 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
General disorders Malaise	6.7% 19/283 • Number of events 37 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	6.6% 21/320 • Number of events 47 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	8.3% 26/312 • Number of events 56 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
General disorders Mucosal inflammation	1.1% 3/283 • Number of events 3 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	1.9% 6/320 • Number of events 7 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	5.8% 18/312 • Number of events 21 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
General disorders Oedema peripheral	1.8% 5/283 • Number of events 5 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	8.8% 28/320 • Number of events 30 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	6.7% 21/312 • Number of events 23 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
General disorders Pyrexia	7.4% 21/283 • Number of events 28 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	7.8% 25/320 • Number of events 26 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	16.0% 50/312 • Number of events 64 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Blood and lymphatic system disorders Leukopenia	3.2% 9/283 • Number of events 12 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	5.0% 16/320 • Number of events 49 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	6.1% 19/312 • Number of events 62 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Infections and infestations Covid-19	11.3% 32/283 • Number of events 32 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	9.4% 30/320 • Number of events 30 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	10.3% 32/312 • Number of events 32 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Infections and infestations Paronychia	0.00% 0/283 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	2.5% 8/320 • Number of events 8 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	6.4% 20/312 • Number of events 20 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Blood and lymphatic system disorders Neutropenia	7.8% 22/283 • Number of events 34 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	11.6% 37/320 • Number of events 77 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	19.9% 62/312 • Number of events 128 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Infections and infestations Upper respiratory tract infection	4.9% 14/283 • Number of events 16 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	4.7% 15/320 • Number of events 17 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	9.3% 29/312 • Number of events 31 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Infections and infestations Urinary tract infection	3.5% 10/283 • Number of events 11 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	6.6% 21/320 • Number of events 24 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	8.3% 26/312 • Number of events 33 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Injury, poisoning and procedural complications Infusion related reaction	2.5% 7/283 • Number of events 7 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	5.0% 16/320 • Number of events 19 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	7.4% 23/312 • Number of events 24 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Nervous system disorders Dysgeusia	7.1% 20/283 • Number of events 20 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	8.8% 28/320 • Number of events 31 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	17.3% 54/312 • Number of events 60 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Investigations Alanine aminotransferase increased	22.3% 63/283 • Number of events 81 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	24.1% 77/320 • Number of events 131 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	25.6% 80/312 • Number of events 129 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Investigations Aspartate aminotransferase increased	18.7% 53/283 • Number of events 78 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	20.6% 66/320 • Number of events 118 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	20.2% 63/312 • Number of events 116 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.
Investigations Blood alkaline phosphatase increased	3.5% 10/283 • Number of events 12 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	2.2% 7/320 • Number of events 13 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.	5.4% 17/312 • Number of events 21 • All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025). All-cause mortality was reported for all randomized subjects regardless of treatment received. Adverse events are reported for participants who received at least 1 dose of study drug (T-DXd, paclitaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) and are summarized according to the treatment arm they were randomised to. This is to provide a summary of the underlying safety profile that patients should expect when initially prescribed treatment.