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. 2025 May 10;17(10):1619.
doi: 10.3390/cancers17101619.

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

Alba Di Leone  1 , Antonio Franco  1 , Virginia Castagnetta  1 , Marta Silenzi  1 , Cristina Accetta  1 , Beatrice Carnassale  1 , Sabatino D'Archi  1 , Flavia De Lauretis  1 , Enrico Di Guglielmo  1 , Federica Gagliardi  1 , Stefano Magno  1 , Francesca Moschella  1 , Maria Natale  1 , Alejandro Martin Sanchez  1 , Lorenzo Scardina  1 , Riccardo Masetti  1 , Gianluca Franceschini  1
Affiliations

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

Alba Di Leone et al. Cancers (Basel). .

Abstract

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.

Keywords: BRCA; luminal B; neoadjuvant chemotherapy; pathologic complete response.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart of patients enrolled in this study.
Figure 2
Figure 2
Distribution of recurrence and mortality.
Figure 3
Figure 3
The survival rates between the two groups: (a) locoregional recurrence (LR-DFS); (b) distant recurrence (DDFS); (c) overall survival (OS).
Figure 3
Figure 3
The survival rates between the two groups: (a) locoregional recurrence (LR-DFS); (b) distant recurrence (DDFS); (c) overall survival (OS).
Figure 4
Figure 4
Overall survival (OS) according to the achievement of pathological complete response (pCR).
Figure 5
Figure 5
Oncological outcomes comparing BRCA WT and PV patients.
See this image and copyright information in PMC

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