# Personalizing Neoadjuvant Chemotherapy: The Impact of BRCA Variants on Pathologic Complete Response in Luminal B Breast Cancer

## TL;DR

This study shows that breast cancer patients with BRCA mutations are more likely to achieve a complete response to pre-surgery chemotherapy, suggesting personalized treatment based on BRCA status.

## Contribution

The study identifies BRCA pathogenic variants as a potential predictor for pathologic complete response in luminal B breast cancer patients undergoing neoadjuvant chemotherapy.

## Key findings

- Patients with BRCA mutations had a significantly higher pathologic complete response rate (20.8%) compared to those without mutations (10.9%).
- BRCA wild-type patients showed better locoregional disease-free survival than those with BRCA pathogenic variants.
- No significant differences were observed in distant disease-free survival or overall survival between the groups.

## Abstract

Breast cancer treatment is not the same for everyone, and understanding who benefits most from specific therapies is crucial. Neoadjuvant chemotherapy, given before surgery, can shrink tumors and improve surgical options, but its effectiveness is variable. In hormone receptor-positive HER2-negative breast cancer, one of the most common subtypes, patients with BRCA gene mutations may respond differently to treatment. This study analyzed nearly 500 patients to investigate whether BRCA mutations influence response to neoadjuvant chemotherapy. The results revealed that patients with BRCA mutations were twice as likely to experience pathologic complete response compared to those without mutations. These findings suggest that BRCA status could help personalize treatment decisions, ensuring that the right patients receive the most effective therapy.

Background: Neoadjuvant chemotherapy (NACT) is effective in downstaging locally advanced breast cancer, improving surgical and oncological outcomes. However, luminal B breast cancer typically exhibits a poorer response to NACT, with only 10–15% of patients achieving a pathologic complete response (pCR). This study investigates whether BRCA pathogenic variants (BRCA PVs) influence pCR rates in luminal B breast cancer patients, aiming to identify potential predictors for personalized treatment strategies. Materials and Methods: This retrospective study included luminal B breast cancer patients who underwent NACT at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS between January 2014 and June 2023. Patients were stratified according to BRCA status: BRCA PVs and BRCA wild-type (WT). Primary endpoint was to evaluate pCR rates, while secondary endpoints included locoregional disease-free survival (LR-DFS), distant disease-free survival (DDFS), and overall survival (OS). Results: In total, 495 patients were enrolled, of whom 442 (89.3%) carried BRCA WT and 53 (10.7%) BRCA PVs. The pCR rate was significantly higher in the BRCA PVs group (20.8% PVs vs. 10.9% WT; p = 0.044). Specifically, the breast pCR rate was 28.3% in BRCA PVs versus 15.4% in BRCA WT (p = 0.030). BRCA WT patients had better 5-year LR-DFS (91.1% WT vs. 79.5% PVs; p = 0.003), while no significant differences were observed in 5-year DDFS or OS. Conclusions: BRCA PVs are associated with a higher pCR rate in luminal B breast cancer patients receiving NACT, suggesting a potential predictive role in tailoring treatment strategies.