Clinical Impact and Genomic Features of Human Epidermal Growth Factor Receptor 2-Low Tumors in BRCA1/2-Mutated Triple-Negative Breast Cancer

被引：0

作者：

Kou, Furong ^{[1
]}

Liu, Huimin ^{[2
]}

Zhang, Yaxin ^{[2
]}

Liao, Xingyu ^{[2
]}

Hu, Li ^{[2
]}

Sun, Jie ^{[2
]}

Zhang, Juan ^{[2
]}

Xu, Ye ^{[2
]}

Yao, Lu ^{[2
]}

Xie, Yuntao ^{[1
,2
]}

机构：

[1] Peking Univ Canc Hosp & Inst, Comprehens Clin Trial Ward, Key Lab Carcinogenesis & Translat Res, Minist Educ Beijing, Beijing, Peoples R China

[2] Peking Univ Canc Hosp & Inst, Familial & Hereditary Canc Ctr, Key Lab Carcinogenesis & Translat Res, Minist Educ Beijing, Beijing, Peoples R China

来源：

JCO PRECISION ONCOLOGY | 2025年 / 9卷

基金：

中国国家自然科学基金;

关键词：

OPEN-LABEL; TRASTUZUMAB; BRCA1; SUSCEPTIBILITY; CAPECITABINE; CHEMOTHERAPY; MULTICENTER; PERTUZUMAB; MUTATIONS; LAPATINIB;

D O I：

10.1200/PO-24-00679

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSEData about the clinical impact of human epidermal growth factor receptor 2 (HER2)-low expression in BRCA1/2-mutated breast cancer (BC) are limited. This study aimed to clarify the clinical relevance of HER2-low in operable BRCA1/2-mutated BC.MATERIALS AND METHODSA total of 495 HER2-negative operable BC with germline BRCA1/2 pathogenic variants treated at our institute between October 2003 and September 2020 were included. HER2-low was defined as immunohistochemistry (IHC) 1+ or 2+/fluorescence in situ hybridization-negative, while HER2-zero as IHC 0. Tumor DNA from 25 BRCA1/2-mutated triple-negative BCs (TNBCs) was subjected to whole-exome sequencing.RESULTSAmong the 186 BRCA1 carriers, 38.8% of TNBC (n = 121) and 52.3% of hormone receptor-positive/HER2-negative BC (n = 65) exhibited HER2-low tumors in the BRCA1 subgroup; among 309 BRCA2 carriers, 44.9% of TNBC (n = 49) and 68.1% of hormone receptor-positive/HER2-negative BC (n = 260) exhibited HER2-low tumors in the BRCA2 subgroup. After a median follow-up of 10.9 years (range, 1.23-19.8 years), among BRCA1-mutated TNBC, HER2-low tumors were significantly associated with better recurrence-free survival (RFS; 10-year RFS: 90.3% v 75.1%; P = .015), distant recurrence-free survival (DRFS; 10-year DRFS: 92.4% v 76.5%; P = .010), and overall survival (OS; 10-year OS: 94.6% v 77.4%; P = .007) than HER2-zero tumors. However, the impact of HER2-low in survival was not observed either in BRCA2-mutated TNBC or in BRCA1- and BRCA2-mutated hormone receptor-positive/HER2-negative BC. Notably, BRCA1-mutated TNBC with HER2-low tumors showed higher homologous recombination deficiency scores than those with HER2-zero tumors.CONCLUSIONBRCA1-mutated TNBC patients with HER2-low tumors have a significantly favorable survival, highlighting the possibility of stratifying these patients into two subgroups on the basis of HER2-low status.

引用

页数：19

共 36 条

[1] Loibl S., Gianni L., HER2-positive breast cancer, Lancet, 389, pp. 2415-2429, (2017)
[2] Tarantino P., Hamilton E., Tolaney S.M., Et al., HER2-low breast cancer: Pathological and clinical landscape, J Clin Oncol, 38, pp. 1951-1962, (2020)
[3] Gianni L., Pienkowski T., Im Y.H., Et al., 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): A multicentre, open-label, phase 2 randomised trial, Lancet Oncol, 17, pp. 791-800, (2016)
[4] Dieras V., Miles D., Verma S., Et al., Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): A descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial, Lancet Oncol, 18, pp. 732-742, (2017)
[5] Murthy R.K., Loi S., Okines A., Et al., Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer, N Engl J Med, 382, pp. 597-609, (2020)
[6] Saura C., Oliveira M., Feng Y.H., Et al., Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with ≥2 HER2-directed regimens: Phase III NALA trial, J Clin Oncol, 38, pp. 3138-3149, (2020)
[7] Swain S.M., Miles D., Kim S.B., Et al., Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study, Lancet Oncol, 21, pp. 519-530, (2020)
[8] Xu B., Yan M., Ma F., Et al., Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): A multicentre, open-label, randomised, controlled, phase 3 trial, Lancet Oncol, 22, pp. 351-360, (2021)
[9] Modi S., Jacot W., Yamashita T., Et al., Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer, N Engl J Med, 387, pp. 9-20, (2022)
[10] Bardia A., Hu X., Dent R., Et al., Trastuzumab deruxtecan after endocrine therapy in metastatic breast cancer, N Engl J Med, 391, pp. 2110-2122, (2024)

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