Abstract 3384: Comprehensive profiling of g<i>BRCA1</i> and g<i>BRCA2</i> variants in Hormone receptor-positive breast cancer of Chinese patients
Authors: Jiajun Ding, Ting Wang, Jing Fan, Huimin Meng, Mengxuan Li, Haoyi Zi, Shuai Wang, Qingxia Li, Yidi Wang, Jing Kong, Fei Yao, Changbing Zhu
Journal: Cancer Research (2025)

Abstract Background and Objective: The identification as well as the interpretation of germline BRCA1 (gBRCA1) and germline BRCA2 (gBRCA2) variants are becoming increasingly critical in the treatment of breast cancer (BC), particularly in cases of hormone receptor-positive BC (HR+ BC). However, a thorough analysis of these variants within the HR+ BC population is still insufficient. Methods: In this single-center retrospective study, a total of 1033 female invasive BC patients getting gBRCAs mutation testing with signatures were enrolled, and 652 of them were HR+ BC patients. Pearson chi-square test and continuous correction chi-square test were used to explored the association between gBRCAs mutation and the characteristics of BC. Then clinical and pathological characteristics related to gBRCAs mutation enrollment on univariate logistic regression were selected for multivariate logistic regression. Results: Overall, 108 Luminal A (LA) BC patients, 411 Luminal B represented HER2 negative (LB-HER2-) BC patients, 133 triple-positive BC (TPBC) patients, 109 HER2 positive (HER2+) patients as well as 272 triple-negative BC (TNBC) patients were enrolled in the study. There were 5.6% (58/1033) patients, 4.7% (49/1033) patients and 10.4% (107/1033) patients carrying BRCA1mut, BRCA2mut and BRCA1/2mut individually. As for HR+ patients, the rates were 2.6% (17/652), 5.2% (34/652) and 7.8% (51/652) respectively. It was the most frequent to found gBRCA1mut in TNBC (14.7% in TNBC compared to 2.36% in non-TNBC, p&amp;lt;0.001) while for gBRCA2mut, it was LB-HER2- BC (6.8% in LB-HER2- BC compared to 3.4% in others). Even if in HR+ BC patients, the rate of gBRCA1mut was higher in ER-low patients compared that in ER-high ones (10.5% vs. 1.8%, p&amp;lt;0.001), while this phenomenon could not be found for gBRCA2 mutation. According to the multivariate logistic regression in overall patients, those with bilateral BC (p=0.007) and PR negative BC (p=0.026) were more likely to be BRCA1mut. Though the difference without statistically significant, it seemed that patients younger than 40 (≤40) (p=0.075) and grade III (p=0.056) tended to be gBRCAmut. While patients ≤40 (p=0.008), in T3 or T4 stage (p=0.034) with higher Ki-67 (p=0.015) were more frequent to be BRCA2mut. Among LB-HER2- patients ≤40 in T3 or T4 stage, the rate of gBRCA2mut increased to 26.9% (7/26), no less than the rate of gBRCA1mut in young TNBC patients (24.7%, 20/81), who were recommended the gBRCAs testing. Conclusion: The clinical and pathological characteristics differed in gBRCA1mut and gBRCA2mut among HR-positive BC patients. The screening for gBRCA2 mutation could be meaningful in young LB-HER2- patients with tumor in T3 or T4 stage. Citation Format: Jiajun Ding, Ting Wang, Jing Fan, Huimin Meng, Mengxuan Li, Haoyi Zi, Shuai Wang, Qingxia Li, Yidi Wang, Jing Kong, Fei Yao, Changbing Zhu. Comprehensive profiling of gBRCA1 and gBRCA2 variants in Hormone receptor-positive breast cancer of Chinese patients [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 3384.