Liu Huimin, Kou Furong, Hu Li, Sun Jie, Zhang Juan, Xu Ye, Yao Lu, Xie Yuntao
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Familial & Hereditary Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Comprehensive Clinical Trial Ward, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
Breast Cancer Res Treat. 2025 Jun;211(3):705-715. doi: 10.1007/s10549-025-07687-6. Epub 2025 Mar 19.
Human epidermal growth factor receptor 2 (HER2)-negative operable breast cancer (BC) patients with germline BRCA1/2 pathogenic variants may benefit from adjuvant olaparib treatment. However, data about how many patients were eligible for olaparib treatment in operable BC patients with BRCA1/2 variants after neoadjuvant chemotherapy (NACT) is lacking.
A total of 341 operable BC with germline BRCA1/2 pathogenic variants who received NACT at our institute between October 2003 and May 2015 were included. Pathological complete response (pCR) and survival were estimated.
Of the 341 BRCA1/2 carriers (BRCA1: 139; BRCA2: 202), 295 (88.1%) cases exhibited HER2-negative BC in the entire cohort. The most common subtype was triple-negative (TN) BC (62.0%) for BRCA1 carriers and hormone receptor (HR)-positive/HER2-negative BC (68.2%) for BRCA2 carriers, respectively. The pCR rate were 39.6% for BRCA1 carriers and 28.2% for BRCA2 carries. The pCR rate in TNBC, HR-positive/HER2-negative BC, and HER2-positive BC were 45.0%, 22.3%, and 45.0% in the entire cohort, respectively. Of these HR-positive/HER2-negative BC patients, 16.0% had non-pCR and exhibited CPS+EG≥3. Overall, 31.9% of the HER2-negative BC cohort were potential candidates for adjuvant olaparib, with 44.0% for BRCA1 carriers and 22.9% for BRCA2 carriers. Furthermore, patients with non-pCR exhibited a worse survival regardless of TNBC and HR-positive/HER2-negative BC disease, especially for HR-positive/HER2-negative BC with CPS+EG≥3.
Approximately one-third of HER2-negative BC patients with BRCA1/2 pathogenic variants are potential candidates for adjuvant olaparib treatment after NACT, with a higher proportion for BRCA1 carriers compared to BRCA2 carriers.
携带种系BRCA1/2致病变异的人表皮生长因子受体2（HER2）阴性可手术乳腺癌（BC）患者可能从奥拉帕利辅助治疗中获益。然而，关于新辅助化疗（NACT）后携带BRCA1/2变异的可手术BC患者中有多少符合奥拉帕利治疗条件的数据尚缺乏。
纳入2003年10月至2015年5月在我院接受NACT的341例携带种系BRCA1/2致病变异的可手术BC患者。评估病理完全缓解（pCR）和生存率。
在341例BRCA1/2携带者（BRCA1：139例；BRCA2：202例）中，整个队列中有295例（88.1%）表现为HER2阴性BC。最常见的亚型分别为BRCA1携带者的三阴性（TN）BC（62.0%）和BRCA2携带者的激素受体（HR）阳性/HER2阴性BC（68.2%）。BRCA1携带者的pCR率为39.6%，BRCA2携带者为28.2%。整个队列中TNBC、HR阳性/HER2阴性BC和HER2阳性BC的pCR率分别为45.0%、22.3%和45.0%。在这些HR阳性/HER2阴性BC患者中，16.0%未达到pCR且CPS+EG≥3。总体而言，HER2阴性BC队列中31.9%是辅助奥拉帕利的潜在候选者，BRCA1携带者为44.0%，BRCA2携带者为22.9%。此外，无论TNBC和HR阳性/HER2阴性BC疾病如何，未达到pCR的患者生存率更差，尤其是CPS+EG≥3的HR阳性/HER2阴性BC患者。
约三分之一携带BRCA1/2致病变异的HER2阴性BC患者是NACT后辅助奥拉帕利治疗的潜在候选者，与BRCA2携带者相比BRCA1携带者比例更高。
