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新辅助化疗后患有生殖系BRCA1/2致病性变异的可手术乳腺癌患者中辅助奥拉帕利治疗的潜在候选者。

Potential candidates for adjuvant olaparib treatment in operable breast cancer patients with germline BRCA1/2 pathogenic variants after neoadjuvant chemotherapy.

作者信息

Liu Huimin, Kou Furong, Hu Li, Sun Jie, Zhang Juan, Xu Ye, Yao Lu, Xie Yuntao

机构信息

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.

出版信息

Breast Cancer Res Treat. 2025 Jun;211(3):705-715. doi: 10.1007/s10549-025-07687-6. Epub 2025 Mar 19.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

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。

方法

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。

结果

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。

结论

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。

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