Should BRCA2 mutation carriers avoid neoadjuvant chemotherapy?

Area of Science:

• Oncology
• Genetics
• Breast Cancer Research

Background:

• BRCA2 germline mutations are often associated with luminal B breast cancer subtype.
• Limited data exist on neoadjuvant chemotherapy efficacy in BRCA2 mutation carriers due to small cohorts and lack of prospective studies.

Purpose of the Study:

• To retrospectively compare pathological complete response (pCR) rates and post-neoadjuvant chemotherapy nodal status between BRCA2 carriers and BRCA1/2-negative (WT) patients with luminal B breast tumors.
• To evaluate the effectiveness of anthracyclines±taxanes-based neoadjuvant chemotherapy in this specific patient population.

Main Methods:

• Retrospective analysis of a 15-year genetic clinic database.
• Inclusion of BRCA2 mutation carriers and BRCA1/2-negative (WT) patients with luminal B tumors treated with neoadjuvant anthracyclines±taxanes-based chemotherapy.
• Comparison of pathological complete response (pCR) rates and rates of post-chemotherapy nodal involvement.

Main Results:

• A pathological complete response (pCR) was observed in 10% of BRCA2 carriers versus 19% of WT patients (p=0.43).
• Post-chemotherapy, 69% of BRCA2 carriers remained node-positive compared to 51% of WT patients (p=0.17).
• BRCA2 germline mutations were associated with a lower pCR and a higher risk of axillary invasion.

Conclusions:

• BRCA2 germline mutations in luminal B breast cancer are linked to a diminished likelihood of achieving pCR with standard neoadjuvant chemotherapy.
• Patients with BRCA2 mutations exhibit an increased risk of persistent axillary lymph node disease post-chemotherapy.
• Alternative treatment strategies and dedicated clinical trials are warranted to optimize neoadjuvant therapy for BRCA2 mutation carriers with luminal B breast cancer.