Breast Unit Group, Medical Oncology Department, Institut Gustave Roussy, Villejuif, France; Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC), Parma, Italy.
Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC), Parma, Italy; Department of Medicine and Surgery, University of Parma, Italy; Medical Oncology, Breast Unit and Cancer Genetics Service, University Hospital of Parma, Italy.
Breast. 2022 Oct;65:145-150. doi: 10.1016/j.breast.2022.07.012. Epub 2022 Jul 31.
HER2-positive breast cancers are rare amongst BRCA mutation carriers. No data exist regarding clinicopathological characteristics and prognosis of this subgroup of patients.
Using a retrospective matched cohort design, we collected data from 700 women who were diagnosed with operable invasive breast cancer from January 2006 to December 2016 and were screened for germline BRCA mutations. Clinicopathological features and survival rates were analyzed by BRCA and HER2 status.
One hundred and fifteen HER2-positive/BRCA mutated cases were evaluated in comparison to the three control groups: HER2-positive/BRCA wild type (n = 129), HER2-negative/BRCA mutated (n = 222), HER2-negative/BRCA wild type (n = 234). HER2-positive breast cancers were more likely to have high histologic grade and high proliferation rate than HER2-negative neoplasms, regardless of BRCA mutation status. An interaction between BRCA mutations and HER2-positive status was found to correlate with worse survival after adjusting for prognostic variables (HR = 3.4; 95% CI: 1.3-16.7).
Co-occurrence of BRCA mutations and HER2-positive status is a poor prognostic factor in patients with early or locally advanced breast cancer. This finding may be a proof of concept that a combined pharmacological intervention directed to these targets could be synergistic.
BRCA 基因突变携带者中 HER2 阳性乳腺癌较为罕见。目前尚无关于此类患者临床病理特征和预后的数据。
采用回顾性匹配队列设计，我们收集了 700 名 2006 年 1 月至 2016 年 12 月期间诊断为可手术性浸润性乳腺癌且筛查为胚系 BRCA 突变的女性患者的数据。通过 BRCA 和 HER2 状态分析临床病理特征和生存率。
与三组对照组（HER2 阳性/BRCA 野生型[n=129]、HER2 阴性/BRCA 突变型[n=222]、HER2 阴性/BRCA 野生型[n=234]）相比，评估了 115 例 HER2 阳性/BRCA 突变病例。无论 BRCA 突变状态如何，HER2 阳性乳腺癌的组织学分级和增殖率均高于 HER2 阴性肿瘤。调整预后变量后，发现 BRCA 突变与 HER2 阳性状态的相互作用与生存不良相关（HR=3.4；95%CI：1.3-16.7）。
在早期或局部晚期乳腺癌患者中，BRCA 基因突变与 HER2 阳性状态同时存在是预后不良的因素。这一发现可能是一个概念验证，即针对这些靶点的联合药物干预可能具有协同作用。
