Application and Comparison of [68Ga]Ga-FAPI-04 PET, [18F]FDG PET, and Contrast-Enhanced MRI in Predicting Pathological Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

Summary

This is a prospective, single-center cohort study enrolling patients with axillary lymph node-positive or locally advanced breast cancer, consistent with the indications for neoadjuvant therapy in routine clinical practice and as recommended by local guidelines. Different neoadjuvant chemotherapy (NAC) regimens were selected according to breast cancer subtypes. All patients underwent 68Ga-FAPI PET/MRI, 18F-FDG PET/CT, and contrast-enhanced MRI before the initiation of NAC and again after completion of NAC but prior to surgery. Surgical treatment was subsequently performed, and pathologic complete response (pCR) was determined based on postoperative histopathologic findings.

For patients with pathologically confirmed axillary lymph node metastasis or locally advanced breast cancer, NAC may reduce TNM stage and even achieve pCR in the breast and/or axilla. This is particularly evident in HER2-positive and triple-negative breast cancer, for which multiple studies have reported pCR rates of approximately 45%-75% and 40%-65%, respectively. NAC may therefore provide opportunities for breast- or axilla-conserving treatment, reducing complications associated with axillary dissection while improving cosmetic outcomes. In addition, NAC enables assessment of tumor sensitivity to systemic therapy.

However, accurate and effective methods for evaluating treatment response after NAC remain lacking. Conventional imaging modalities, such as ultrasound and MRI, demonstrate limited sensitivity and specificity. Although 18F-FDG PET/CT can be used to monitor pathologic response after NAC, its diagnostic performance is influenced by inflammation and metabolic factors, shows limited sensitivity for small lesions, and is relatively costly; thus, it is not widely used in clinical practice for response evaluation.

Fibroblast activation protein (FAP) is predominantly expressed in cancer-associated fibroblasts (CAFs) within the tumor stroma and promotes tumor growth, invasion, and drug resistance through multiple mechanisms. Under physiologic conditions, FAP expression is low in most adult tissues but is significantly upregulated in breast cancer. Moreover, 68Ga-FAPI has demonstrated superior imaging performance compared with \^18F-FDG in breast cancer.

This study aims to evaluate the feasibility and accuracy of 68Ga-FAPI PET/MRI, compared with 18F-FDG PET/CT and contrast-enhanced breast MRI, in assessing response to NAC in breast cancer, thereby providing additional evidence for clinical decision-making. This is a dynamic cohort study that plans to enroll 27 patients with operable or locally advanced breast cancer, tumor size \>5 cm, or lymph node-positive disease. Baseline imaging with 68Ga-FAPI PET/MRI, 18F-FDG PET/CT, and contrast-enhanced breast MRI will be performed within 10 days before initiation of NAC. Patients will then receive standard NAC according to subtype and clinical guidelines. Follow-up imaging with the same modalities will be conducted between 2 weeks after completion of NAC and within 10 days before surgery. Surgery will then be performed, and patients will be classified into pCR and non-pCR groups based on postoperative pathology. Imaging findings from 68Ga-FAPI PET/MRI, 18F-FDG PET/CT, and breast MRI will be compared with histopathologic results to evaluate their ability to predict pCR.

Postoperative follow-up will be conducted to assess prognosis, supported by evidence from MRI, CT, ultrasound, and laboratory examinations. The minimum follow-up duration will be ≥12 months.

Conditions

• Breast Cancer

Interventions

DRUG

68Ga-FAPI-04

A fibroblast activation protein (FAP) -targeted PET imaging agent

DRUG

18F-FDG

A general glucose metabolism imaging agent

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  lead OTHER

Principal Investigators

• Chunping Liu · Tongji Medical College, Huazhong University of Science and Technology

Study Design

Allocation

NA

Purpose

DIAGNOSTIC

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-04-01

Primary Completion

2025-12-31

Completion

2026-04-01

Countries

• China

Study Locations