Trial Outcomes & Findings for Omission of Surgery in Clinically Low-risk HER2positive Breast Cancer With High HER2 Addiction and a Complete Response Following Standard Anti-HER2-based Neoadjuvant Therapy (NCT NCT04578106)

Last Updated: 2026-01-06

Results Overview

To estimate the loco-regional invasive disease-free survival (LR-IDFS) at 3-year of patients who achieve a complete response based on imaging and a stereotactic-guided vacuum-assisted breast biopsy, and omit loco-regional surgery.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

3 years

Results posted on

2026-01-06

Participant Flow

Overall, 20 patients were screened for the study in a single study centre (clinical setting) over the duration of 18 months. A total of 5 patients were finally selected for the study treatment after meeting all the inclusion criteria and signing the ICF

Out of 20 patients screened, 13 patients did not fulfill the study criteria (PAM50 subtype other than HER2-Enriched, ERBB2 high, liver metastasis, multicentric tumor). Finally only 5 patients that fulfilled all eligibility criteria and signed the ICF were included

Participant milestones

Participant milestones
Measure	Treatment Arm Treatment in women with primary operable HER2-positive, HER2-enriched(HER2-E)/ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression): * Tumor size ≤ 2 cm: Paclitaxel/trastuzumab/pertuzumab (TDM-1 if residual disease) * Tumor size \> 2 cm and ≤ 4cm: Antracycline based chemotherapy followed by Paclitaxel/trastuzumab/pertuzumab (TDM-1 if residual disease)
Study treatment STARTED	5
Study treatment COMPLETED	5
Study treatment NOT COMPLETED	0
Follow-up after 1 year STARTED	5
Follow-up after 1 year COMPLETED	4
Follow-up after 1 year NOT COMPLETED	1
Follow up at 3 yrs STARTED	4
Follow up at 3 yrs COMPLETED	0
Follow up at 3 yrs NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Arm Treatment in women with primary operable HER2-positive, HER2-enriched(HER2-E)/ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression): * Tumor size ≤ 2 cm: Paclitaxel/trastuzumab/pertuzumab (TDM-1 if residual disease) * Tumor size \> 2 cm and ≤ 4cm: Antracycline based chemotherapy followed by Paclitaxel/trastuzumab/pertuzumab (TDM-1 if residual disease)
Follow-up after 1 year Lost to Follow-up	1

Baseline Characteristics

Omission of Surgery in Clinically Low-risk HER2positive Breast Cancer With High HER2 Addiction and a Complete Response Following Standard Anti-HER2-based Neoadjuvant Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Arm n=5 Participants Treatment in women with primary operable HER2-positive, HER2-enriched(HER2-E)/ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression): * Tumor size ≤ 2 cm: Paclitaxel/trastuzumab/pertuzumab (TDM-1 if residual disease) * Tumor size \> 2 cm and ≤ 4cm: Antracycline based chemotherapy followed by Paclitaxel/trastuzumab/pertuzumab (TDM-1 if residual disease)
Age, Customized >= 40 yrs	5 participants n=9 Participants
Sex: Female, Male Female	5 Participants n=9 Participants
Sex: Female, Male Male	0 Participants n=9 Participants
Race/Ethnicity, Customized Caucasian	5 participants n=9 Participants
Region of Enrollment Spain	5 participants n=9 Participants
Menopausal Status Postmenopausal (min 12 mnths without menses before neoadyuvance treatment)	4 participants n=9 Participants
Menopausal Status premenopausal	1 participants n=9 Participants
ECOG baseline Grade 0	4 participants n=9 Participants
ECOG baseline Grade 1	1 participants n=9 Participants
Previous cancer history Yes	0 participants n=9 Participants
Previous cancer history No	5 participants n=9 Participants

PRIMARY outcome

Timeframe: 3 years

Population: After completion of neoadjuvant therapy with paclitaxel and Trastuzumab/pertuzumab, out of 5 patients, only 3 patients showed complete response (assessed by MRI) and 2 patients (no stereo-guided VAB assessment) did not undergo surgery. However, the participants were lost to follow-up before 3-year assessments, so no evaluable 3-year survival data are available

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pCR assessment was done following surgery after neoadjuvant therapy with paclitaxel and trastuzumzb/pertuzumab prior to adjuvant therapy

Population: While total number of HR positive patients and HR negative patients in the overall treatment group is 2 and 3 respectively, only 1 patient in the former and 2 patients in the later group were evaluated for pCR at surgery

rate of pathological complete response (pCR) between the treatment groups by HR status

Outcome measures

Outcome measures
Measure	Omision of Surgery (Complete Response) n=1 Participants After completion of neoadjuvant therapy, if no invasive tumor cells and no in situ disease are identified in the stereotactic-guided VAB (complete response), patients will be eligible to omit loco-regional surgery	HR Negative n=2 Participants Patients that are hormone receptor (HR) negative (assessed at baseline)	Patients With Omission of Surgery (Assessment at Screening) Of the treatment population, those patients with omission of surgery post neoadjuvant therapy. The assessment time period is at screening	Patients With Omission of Surgery (Assessment After Adjuvant Therapy) Of the treatment population, those patients who underwent surgery post neoadjuvant therapy. The assessment time period is after adjuvant therapy
pCR Rate	0 Participants	2 Participants	—	—

SECONDARY outcome

Timeframe: The questionnaire was filled by the patients at screening and post adjuvant therapy.

Population: Out of the treatment population, 3 patients underwent surgery post neoadjuvant therapy (standard therapy) and 2 patients did not undergo surgery (investigative therapy). All the patients of both the groups completed the patient reported outcomes questionaire at screening. 1 patient from the patient group that underwent surgery did not complete the questionnaire after adjuvant therapy.

The EORTC QLQ-C30 was used to assess Health-Related Quality of Life (QoL). The measure consists of five functional scales (physical, role, cognitive, emotional, and social). For this study, raw scores were used without any transformation. The functional scales consist of multiple items (questions 1-28) scored on a 1-4 scale (1 = not at all, 4 = very much). Higher scores indicate worse functioning. To assess the effect of standard therapy (surgery after neoadjuvant therapy) vs. investigational therapy (omission of surgery), the global health status is reported in each of these populations before and after treatment. The Global Health Status (GHS) score is derived from two items (Q29 and Q30), each scored on a 1-7 scale (1 = very poor, 7 = excellent). Scoring method: GHS = (Q29 + Q30) / 2 Raw score range: Minimum = (1 + 1) / 2 = 1; Maximum = (7 + 7) /2 = 7

Outcome measures

Outcome measures
Measure	Omision of Surgery (Complete Response) n=3 Participants After completion of neoadjuvant therapy, if no invasive tumor cells and no in situ disease are identified in the stereotactic-guided VAB (complete response), patients will be eligible to omit loco-regional surgery	HR Negative n=2 Participants Patients that are hormone receptor (HR) negative (assessed at baseline)	Patients With Omission of Surgery (Assessment at Screening) n=2 Participants Of the treatment population, those patients with omission of surgery post neoadjuvant therapy. The assessment time period is at screening	Patients With Omission of Surgery (Assessment After Adjuvant Therapy) n=2 Participants Of the treatment population, those patients who underwent surgery post neoadjuvant therapy. The assessment time period is after adjuvant therapy
Patient Reported Outcomes (Global Health Status)	5 score on a scale Interval 5.0 to 6.0	4 score on a scale Interval 3.5 to 4.5	5.25 score on a scale Interval 4.5 to 6.0	5 score on a scale Interval 4.0 to 6.0

Adverse Events

Treatment Arm (Treatment With Paclitaxel)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Treatment Arm (Treatment With Trastuzumab)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Treatment Arm (Treatment With Pertuzumab)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Treatment Arm (Adjuvant Treatment With TDM1)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Tomas Pascual

Hospital Clínic de Barcelona

Phone: 932275400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Treatment Arm (Treatment With Paclitaxel) n=5 participants at risk Treatment in women with primary operable HER2-positive, HER2-enriched(HER2-E)/ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression): * Tumor size ≤ 2 cm: Paclitaxel/trastuzumab/pertuzumab (TDM-1 if residual disease) * Tumor size \> 2 cm and ≤ 4cm: Antracycline based chemotherapy followed by Paclitaxel/trastuzumab/pertuzumab (TDM-1 if residual disease)	Treatment Arm (Treatment With Trastuzumab) n=5 participants at risk Treatment in women with primary operable HER2-positive, HER2-enriched(HER2-E)/ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression): * Tumor size ≤ 2 cm: Paclitaxel/trastuzumab/pertuzumab (TDM-1 if residual disease) * Tumor size \> 2 cm and ≤ 4cm: Antracycline based chemotherapy followed by Paclitaxel/trastuzumab/pertuzumab (TDM-1 if residual disease)	Treatment Arm (Treatment With Pertuzumab) n=5 participants at risk Treatment in women with primary operable HER2-positive, HER2-enriched(HER2-E)/ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression): * Tumor size ≤ 2 cm: Paclitaxel/trastuzumab/pertuzumab (TDM-1 if residual disease) * Tumor size \> 2 cm and ≤ 4cm: Antracycline based chemotherapy followed by Paclitaxel/trastuzumab/pertuzumab (TDM-1 if residual disease)	Treatment Arm (Adjuvant Treatment With TDM1) n=3 participants at risk TDM-1 administered on Day 1 of a 3-week cycle q3w at a doce of 3.6 mg/kg IV as adjuvant treatment in patients of the treatment population with non-complete response in the neoadjuvant setting
Blood and lymphatic system disorders decrease in hemoglobin	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	33.3% 1/3 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Hepatobiliary disorders increase of total bilirubine	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	33.3% 1/3 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Hepatobiliary disorders alat increase	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	100.0% 3/3 • Number of events 4 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Hepatobiliary disorders asat increase	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	66.7% 2/3 • Number of events 2 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Gastrointestinal disorders epigastralgia	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	66.7% 2/3 • Number of events 2 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Hepatobiliary disorders increase of alkaline phosphatase	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	66.7% 2/3 • Number of events 2 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Skin and subcutaneous tissue disorders alopecia	80.0% 4/5 • Number of events 7 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
General disorders asthenia	40.0% 2/5 • Number of events 2 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	33.3% 1/3 • Number of events 3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Metabolism and nutrition disorders dysguesia	40.0% 2/5 • Number of events 2 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Blood and lymphatic system disorders anemia	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Musculoskeletal and connective tissue disorders arthralgia	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Nervous system disorders headache	40.0% 2/5 • Number of events 2 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Gastrointestinal disorders diarrhea	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	80.0% 4/5 • Number of events 4 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	80.0% 4/5 • Number of events 4 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Skin and subcutaneous tissue disorders erythema face and hands	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Skin and subcutaneous tissue disorders erythema arms and hands	60.0% 3/5 • Number of events 3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Skin and subcutaneous tissue disorders feet erythema	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Nervous system disorders hands neurotoxicity	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Metabolism and nutrition disorders hiporexya	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	33.3% 1/3 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Respiratory, thoracic and mediastinal disorders mucositis	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Nervous system disorders neurotoxicity in foot	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Respiratory, thoracic and mediastinal disorders occasional epistaxis	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Skin and subcutaneous tissue disorders onychodystrophy	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Skin and subcutaneous tissue disorders onycholysis	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Skin and subcutaneous tissue disorders plantar erythema	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Respiratory, thoracic and mediastinal disorders cough	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Skin and subcutaneous tissue disorders erythematous reaction	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Musculoskeletal and connective tissue disorders muscle pain	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	20.0% 1/5 • Number of events 1 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/3 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)
Blood and lymphatic system disorders plaquetopenia	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	0.00% 0/5 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)	33.3% 1/3 • Number of events 2 • Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)