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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: 68Ga-FAPI-04; Drug: 18F-FDG

Detailed Description

Breast cancer is one of the most common malignancies among women worldwide, with persistently high incidence and mortality rates, posing a serious threat to women's health. With the continuous advancement of treatment strategies, neoadjuvant therapy (NAC) has become increasingly important in the comprehensive management of breast cancer. NAC refers to the use of chemotherapy, targeted therapy, or immunotherapy prior to surgery to reduce tumor size and downstage disease, thereby improving resectability and providing opportunities for breast- or axilla-conserving treatment . This approach is particularly beneficial for patients with HER2-positive and triple-negative breast cancer, in whom NAC has demonstrated significant advantages in improving the rate of pathologic complete response (pCR). Studies have reported that the pCR rate can reach 50%-75% in HER2-positive breast cancer and 40%-65% in triple-negative breast cancer. Achieving pCR not only improves patient prognosis but also reduces the extent of surgery, minimizes complications associated with axillary dissection, and better meets patients' expectations for cosmetic outcomes and quality of life.

Despite these advances, accurate evaluation of treatment response after NAC remains challenging. Conventional imaging modalities, such as ultrasound and MRI, have limited sensitivity and specificity and may not accurately reflect post-treatment tumor changes. Although 18F-FDG PET/CT offers advantages in assessing tumor metabolic activity , its diagnostic performance is susceptible to interference from inflammation and metabolic factors, has limited sensitivity for small lesions, and is relatively costly, which restricts its widespread clinical application. Therefore, the development of more accurate and cost-effective methods for response evaluation remains an urgent need in the field of neoadjuvant therapy for breast cancer.

In recent years, with the rapid development of molecular imaging, fibroblast activation protein (FAP) has emerged as a promising biomarker. FAP is predominantly expressed in carcinoma-associated fibroblasts (CAFs) within the tumor stroma, showing high expression in breast cancer tissues but minimal expression in normal tissues. FAP has been shown to play a crucial role in tumor initiation, progression, and drug resistance by promoting tumor microenvironment formation and immune evasion . Positron emission tomography/magnetic resonance imaging (PET/MRI) using ^68Ga-labeled fibroblast activation protein inhibitors (68Ga-FAPI) enables more precise assessment of tumor burden and provides a novel approach for predicting and evaluating the response to NAC.

In summary, this study utilizes 68Ga-FAPI PET imaging to comparatively evaluate the differences among 18F-FDG PET, 68Ga-FAPI PET, and contrast-enhanced breast MRI before and after treatment in assessing response to NAC in breast cancer. The study aims to compare the value of these three imaging modalities in treatment response evaluation and to explore the role of FAP expression in predicting the efficacy of NAC in patients with axillary lymph node metastasis or locally advanced breast cancer. By integrating the biological characteristics of FAP with 68Ga-FAPI PET imaging, this study is expected to provide new insights into precise response assessment and individualized treatment strategies for breast cancer, thereby advancing the field of breast cancer management.

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430022
      • China, Hubei Province

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Female, aged 18-70 years Pathologically confirmed primary breast cancer TNM stage T2-4N0M0/T1-4N1-3M0 No prior treatment No severe hematologic, cardiac, pulmonary, hepatic, or renal dysfunction, and no immunodeficiency diseases Patients must have good physical condition, ECOG score of 0-1 Female patients of childbearing potential must agree to use effective contraception during the study Signed written informed consent

Exclusion Criteria:

Unwilling to undergo 68Ga-FAPI PET/MRI scan Unable to tolerate chemotherapy or surgery Previous history of other malignancies or prior antitumor treatment Evidence of distant metastasis Immunodeficiency or autoimmune disease History of monoclonal antibody allergy Pregnant or breastfeeding women Presence of active infection Patients with mental illness or cognitive impairment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: neoadjuvant chemotherapy; It is planned to include 27 patients with operable or locally advanced breast cancer, tumor size >5 cm, or positive lymph nodes. Within ten days before the start of neoadjuvant therapy, baseline examinations including 68Ga-FAPI PET/MRI, 18F-FDG PET/CT, and contrast-enhanced breast MRI will be completed. Subsequently, standard neoadjuvant therapy will be administered according to treatment guidelines based on each subtype. Two weeks after neoadjuvant therapy until ten days before surgery, 68Ga-FAPI PET/MRI, 18F-FDG PET/CT, and contrast-enhanced breast MRI preoperative examinations will be completed, followed by surgical treatment. Finally, based on postoperative pathological results, patients will be divided into the pCR group and non-pCR group, and the results of 68Ga-FAPI PET/MRI, 18F-FDG PET/CT, and breast MRI will be compared with pathological results to evaluate their ability to predict pCR.

Drug: 68Ga-FAPI-04; A fibroblast activation protein (FAP) -targeted PET imaging agent; Drug: 18F-FDG; A general glucose metabolism imaging agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
18F-FDG PET analysis	PET parameter (SUV in g/ml) changes between both scans will be measured.	Baseline and 21-28 days after the last cycle of neoadjuvant chemotherapy (each cycle is 21days)
18F-FDG PET analysis	PET parameter (MTV in cm3) changes between both scans will be measured.	Baseline and 21-28 days after the last cycle of neoadjuvant chemotherapy (each cycle is 21days)
18F-FDG PET analysis	PET parameter (TLG in g/ml*cm3) changes between both scans will be measured.	Baseline and 21-28 days after the last cycle of neoadjuvant chemotherapy (each cycle is 21days)
68Ga-FAPI-04 PET analysis	PET parameter (SUV in g/ml) changes between both scans will be measured.	Baseline and 21-28 days after the last cycle of neoadjuvant chemotherapy (each cycle is 21days)
68Ga-FAPI-04 PET analysis	PET parameter (MTV in cm3) changes between both scans will be measured.	Baseline and 21-28 days after the last cycle of neoadjuvant chemotherapy (each cycle is 21days)
68Ga-FAPI-04 PET analysis	PET parameter (TLG in g/ml*cm3) changes between both scans will be measured.	Baseline and 21-28 days after the last cycle of neoadjuvant chemotherapy (each cycle is 21days)

Collaborators and Investigators

• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
• Investigators: Study Director: Chunping Liu, Tongji Medical College, Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2025
• Primary Completion (Actual): December 31, 2025
• Study Completion (Actual): April 1, 2026

Study Registration Dates

• First Submitted: April 14, 2026
• First Submitted That Met QC Criteria: April 20, 2026
• First Posted (Actual): April 28, 2026

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Carbohydrates; Deoxyglucose; Deoxy Sugars; Fluorodeoxyglucose F18; 68Ga-FAPI
• Other Study ID Numbers: LCP-2505

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No