Department of Oncology, Mayo Clinic, Rochester, MN.
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN.
J Clin Oncol. 2023 Mar 20;41(9):1703-1713. doi: 10.1200/JCO.22.01239. Epub 2023 Jan 9.
To estimate the risk of contralateral breast cancer (CBC) among women with germline pathogenic variants (PVs) in , , , , and .
The study population included 15,104 prospectively followed women within the CARRIERS study treated with ipsilateral surgery for invasive breast cancer. The risk of CBC was estimated for PV carriers in each gene compared with women without PVs in a multivariate proportional hazard regression analysis accounting for the competing risk of death and adjusting for patient and tumor characteristics. The primary analyses focused on the overall cohort and on women from the general population. Secondary analyses examined associations by race/ethnicity, age at primary breast cancer diagnosis, menopausal status, and tumor estrogen receptor (ER) status.
Germline , , and PV carriers with breast cancer were at significantly elevated risk (hazard ratio > 1.9) of CBC, whereas only the PV carriers with ER-negative breast cancer had elevated risks (hazard ratio, 2.9). By contrast, PV carriers did not have significantly increased CBC risks. African American PV carriers had similarly elevated risks of CBC as non-Hispanic White PV carriers. Among premenopausal women, the 10-year cumulative incidence of CBC was estimated to be 33% for , 27% for , and 13% for PV carriers with breast cancer and 35% for PV carriers with ER-negative breast cancer. The 10-year cumulative incidence of CBC among postmenopausal PV carriers was 12% for , 9% for , and 4% for .
Women diagnosed with breast cancer and known to carry germline PVs in , , , or are at substantially increased risk of CBC and may benefit from enhanced surveillance and risk reduction strategies.
评估携带 、 、 、 和 种系致病性变异（PVs）的女性发生对侧乳腺癌（CBC）的风险。
本研究纳入了 15104 例在 CARRIERS 研究中接受同侧手术治疗浸润性乳腺癌的前瞻性随访女性。在多变量比例风险回归分析中，与无 PVs 的女性相比，比较了每个基因中 PV 携带者的 CBC 风险，该分析考虑了死亡的竞争风险，并调整了患者和肿瘤特征。主要分析集中在总体队列和一般人群中的女性。次要分析检查了种族/民族、原发性乳腺癌诊断时的年龄、绝经状态和肿瘤雌激素受体（ER）状态的相关性。
携带乳腺癌的种系 、 、 和 PV 携带者发生 CBC 的风险显著升高（风险比>1.9），而仅携带 ER 阴性乳腺癌的 PV 携带者发生 CBC 的风险升高（风险比，2.9）。相比之下， PV 携带者没有显著增加的 CBC 风险。非洲裔美国 PV 携带者发生 CBC 的风险与非西班牙裔白人 PV 携带者相似。在绝经前女性中，携带乳腺癌的 、 、 和 PV 携带者的 10 年累积 CBC 发生率估计分别为 33%、27%和 13%，携带 ER 阴性乳腺癌的 PV 携带者为 35%。绝经后 PV 携带者的 10 年累积 CBC 发生率分别为 12%、9%和 4%。
诊断患有乳腺癌且已知携带 、 、 、 种系 PVs 的女性发生 CBC 的风险显著增加，可能受益于增强的监测和风险降低策略。
