BRCA1 和 BRCA2 致病性变异携带者所患的乳腺癌具有不同的病理特征和突变特征，可能导致对化疗的不同反应。我们比较了 1426 名接受临床 I-III 期乳腺癌治疗的女性（92 名 [6.5%] BRCA1 和 73 名 [5.1%] BRCA2）中 BRCA1/2 变异携带者和非携带者之间 NAC 后的病理完全缓解 (pCR) 率2013 年 11 月至 2022 年 1 月在纪念斯隆凯特琳癌症中心接受 NAC 治疗，随后进行手术。大多数人接受阿霉素/环磷酰胺/紫杉醇治疗（93%）； BRCA1/2 携带者更有可能接受卡铂治疗 (p<<0.001)。总体而言，42% 的 BRCA1 携带者、21% 的 BRCA2 携带者和 26% 的非携带者实现了 pCR (p = 0.001)。在临床淋巴结阳性 (cN ) 患者中，与非携带者相比，BRCA1/2 携带者的淋巴结 pCR 更为常见（53/96 [55%] vs. 371/856 [43%]，p = 0.015）。这种差异见于 HR /HER2-（非携带者的 36% 与 20%；p = 0.027）和 TN 亚型（非携带者的 79% 与 45%；p< 0.001）。在对整个队列的多变量分析中，BRCA1 状态以及 TN 和 HER2 亚型与 pCR 独立相关。这些数据表明，与 BRCA2 携带者和散发性疾病患者相比，BRCA1 携带者可能更有可能通过 NAC 实现总体和淋巴结 pCR。需要对更大的 BRCA1/2 突变携带者队列进行进一步研究，因为在按亚型分层并根据临床相关因素进行调整的敏感性分析中，小样本量可能会限制检测突变状态与 pCR 之间显着关联的能力。© 2024 . 作者。

BRCA1 and BRCA2 pathogenic variant carriers develop breast cancers with distinct pathological characteristics and mutational signatures that may result in differential response to chemotherapy. We compared rates of pathologic complete response (pCR) after NAC between BRCA1/2 variant carriers and noncarriers in a cohort of 1426 women (92 [6.5%] BRCA1 and 73 [5.1%] BRCA2) with clinical stage I-III breast cancer treated with NAC followed by surgery from 11/2013 to 01/2022 at Memorial Sloan Kettering Cancer Center. The majority received doxorubicin/cyclophosphamide/paclitaxel therapy (93%); BRCA1/2 carriers were more likely to receive carboplatin (p < 0.001). Overall, pCR was achieved in 42% of BRCA1 carriers, 21% of BRCA2 carriers, and 26% of noncarriers (p = 0.001). Among clinically node-positive (cN+) patients, nodal pCR was more frequent in BRCA1/2 carriers compared to noncarriers (53/96 [55%] vs. 371/856 [43%], p = 0.015). This difference was seen in HR+/HER2- (36% vs. 20% of noncarriers; p = 0.027) and TN subtypes (79% vs. 45% of noncarriers; p < 0.001). In a multivariable analysis of the overall cohort, BRCA1 status, and TN and HER2+ subtypes were independently associated with pCR. These data indicate that BRCA1 carriers may be more likely to achieve overall and nodal pCR in response to NAC compared with BRCA2 carriers and patients with sporadic disease. Further studies with a larger cohort of BRCA1/2 mutation carriers are needed, as a small sample size may have a restricted ability to detect a significant association between mutational status and pCR in sensitivity analyses stratified by subtype and adjusted for clinically relevant factors.© 2024. The Author(s).