BRCA pathogenic variants and response in early TNBC patients treated with neoadjuvant pembrolizumab: outcomes of the BRCAPATH study.

BACKGROUND

Current data on BRCA status and response to neoadjuvant pembrolizumab plus chemotherapy are limited. This study evaluated the association between BRCA status and pathological complete response (pCR) in patients with early triple-negative breast cancer (TNBC).

METHODS

BRCAPATH was a French multicenter retrospective study including 288 patients with early TNBC; 234 received neoadjuvant pembrolizumab plus chemotherapy and 54 received chemotherapy alone. pCR was defined as ypT0/TisN0 (TNM 8th edition). Associations between BRCA status and pCR were evaluated using Fisher's exact test and multivariable logistic regression. Survival was analyzed using the Kaplan-Meier method.

RESULTS

In the pembrolizumab-treated cohort, 35 patients (15.0%) carried BRCA pathogenic variants (PV) and pCR was achieved in 88.6% of BRCA PV carriers versus 52.1% of non-carriers (p < 0.001). In multivariable analysis, BRCA PV remained independently associated with pCR (OR 8.47, 95% CI 2.65-27.04; p < 0.001). In exploratory subgroup analyses, BRCA1 pathogenic variants remained significantly associated with pCR, whereas findings for BRCA2 were limited by the small number of carriers. No statistically significant survival difference was observed for BRCA PV carriers.

CONCLUSION

BRCA PV, particularly BRCA1, were strongly associated with pCR in pembrolizumab-treated early TNBC. These findings should be considered hypothesis-generating and warrant confirmation in larger prospective cohorts.