Mutational Status is Associated with a Higher Rate of Pathologic Complete Response After Neoadjuvant Chemotherapy in Hormone Receptor-Positive Breast Cancer

Background. Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) occurs in up to 20% of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancers. Whether this differs among BRCA mutation carriers is uncertain. This study compared pCR between BRCA1/2 mutation carriers and matched sporadic control subjects.Methods. From November 2013 to January 2022, this study identified 522 consecutive women with clinical stage I to III HR+/HER2- breast cancer treated with NAC and surgery. The study matched BRCA1/2 mutation carriers 1:2 to non-carriers in terms of age, clinical tumor (cT) and nodal (cN) stage, and differentiation. Two-sample non-parametric tests compared baseline characteristics. Multivariable logistic regression assessed pCR (i.e., ypT0/ispN0) by BRCA1/2 mutational status.Results. Of the 522 women (median age, 50 years), 59 had BRCA1/2 mutations, 78% of which were clinically node positive. Anthracycline-based NAC was administered to 97%. More BRCA1/2 mutation carriers were younger, had cT1 tumors, and had poorly differentiated disease. After matching, 58 BRCA1/2 mutation carriers were similar to 116 non-carriers in terms of age (p = 0.6), cT (p = 0.9), cN stage (p = 0.7), and tumor differentiation (p > 0.9). Among the mutation carriers, the pCR rate was 15.5% for BRCA1/2, 38% (8/21) for BRCA1, and 2.7% (1/37) for BRCA2 versus 7.8% (9/116) for the non-carriers (p < 0.001). After NAC, 5 (41.7%) of the 12 BRCA1 mutation carriers converted to pN0 versus 10 (37%) of the 27 BRCA2 mutation carriers and 19 (20.9%) of the 91 non-carriers (p = 0.3). In the multivariable analysis, BRCA1 mutation status was associated with higher odds of pCR than non-carrier status (odds ratio [OR] 6.31; 95% confidence interval [CI] 1.95-20.5; p = 0.002), whereas BRCA2 mutation status was not (OR 0.45; 95% CI 0.02-2.67; p = 0.5).Conclusions. This study showed that BRCA1 mutation carriers with HR+/HER2- breast cancers have a higher rate of pCR than sporadic cancers and may derive greater benefit from chemotherapy. The use of NAC to downstage these patients should be considered.

Automated summary

This study compared the pathologic complete response (pCR) between BRCA1/2 mutation carriers and sporadic breast cancer patients, and found that BRCA1 mutation carriers had a higher rate of pCR and may derive greater benefit from chemotherapy.