Abstract 3382: The predictive effect of gBRCAs mutations on rates of pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in Chinese breast cancer (BC) patients: a single-center study in Xijing Hospital, Northwest China

Abstract Background and Objective: The link between germline BRCA (gBRCA) mutations and the effectiveness of neoadjuvant therapy (NAC) in early-stage breast cancer (BC) is debated. It prompted us to conduct this retrospective study to determine NAC efficacies according to gBRCA variant status overall or further by BC molecular subtypes. Methods: A cohort of 452 female patients receiving standard NAC and following surgery with gBRCAs mutational signatures were enrolled in this study. Pearson Chi-square test, continuous correction chi-square test and fisher's exact test were used to explored the association between gBRCA1/2 mutation and the response to NAC. Results: Overall, 131 patients with triple negative breast cancer (TNBC), 215 patients with Luminal B (HER2- or HER2+) BC as well as 57 HER2+ patients were included. All enrolled patients classified as stageII-III. 60.6% (20/33) of gBRCA1 mutation (gBRCA1mut) patients, 28.6% (8/28) of gBRCA2 mutation (gBRCA2mut) patients and 39.6% (155/391) of noncarriers patients achieved pathological complete response (pCR) (p=0.049). For achieving RCB 0/I, the rates were 69.7% (23/33), 39.3% (11/28) and 50.4% (197/391) respectively (p=0.045). Among HER2- patients, gBRCA1mut patients were more likely to be pCR compared to non-gBRCA1mut carriers (53.8% vs. 25.2%, p=0.005), so as in gBRCA1/2mut patients compared to non-gBRCA1/2mut carriers (42.9% vs. 25.7%, p=0.023). In Luminal B (HER2-) patients, only gBRCA1mut was associated with better pCR rate (57.1% in gBRCA1mut patients compared to 13.9% in non-gBRCA1mut patients, p=0.013). While in TNBC patients, pCR was more frequent in gBRCA1/2mut patients compared to noncarriers (60.7% vs. 37.9%, p=0.034). Additionally, in clinically node-positive patients, in spite of the difference was not statistically significant, gBRCA2mut patients tended to be worse response to NAC compared to non-gBRCA2mut patients (0.0% vs. 29.3%, p=0.077). Conclusion: Though the outcome of a single-center study with small sample size was restricted, it could be found that BRCA1mut patients had better response to NAC, while BRCA2mut patients achieved less from NAC. Citation Format: Jing Fan, Ting Wang, Jiajun Ding, Yidi Wang, Mengxuan Li, Huimin Meng, Jing Kong, Haoyi Zi, Qingxia Li, Shuai Wang, Fei Yao, Changbing Zhu. The predictive effect of gBRCAs mutations on rates of pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in Chinese breast cancer (BC) patients: a single-center study in Xijing Hospital, Northwest China [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3382.