新型抗HER2药物的开发为乳腺癌女性提供了新的治疗选择，包括HER2表达较低的情况。转移性HER2低表达乳腺癌的流行病学和临床结果尚未被全面描述。我们设计了一项回顾性队列研究，对2010-2017年国家癌症数据库（NCDB）中HER2低和HER2负的原发转移乳腺癌患者进行系统性治疗，并比较其总生存期。多元Cox回归模型用于估计危险比（HR），并根据社会经济和临床因素进行调整。共有30,929名患者中，20,636名（66.7％）为HER2低，10,293名（33.3％）为HER2负。在荷尔蒙受体状态分层时，HER2低肿瘤在HR + / HER2-人群中占18,066例（69.7％），在HR- / HER2-人群中占2570例（51.4％）。 HER2低肿瘤的患病率在各个种族群体中相似，其中Hispanic人群的患病率略低。与HER2负肿瘤相比，HER2低肿瘤的女性总生存期（OS）更长，在HR阳性组（中位生存时间39.0个月 vs. 37.1个月; 调整HR：0.95，95％CI（0.91-0.98））和HR阴性组（中位生存时间15.8个月 vs. 14.1个月; 调整HR：0.92，95％CI（0.86-0.98））中均如此。生存优势主要在首次治疗中接受化疗的患者中观察到（HR 0.92 95％CI（0.88-0.96）vs. 0.99 95％CI（0.94-1.04），p-交互作用=0.04）。总之，HER2低肿瘤，在激素受体状态不同的情况下，与HER2负肿瘤相比，原发转移时的存活期更长。生存优势主要在首次接受化疗的患者中观察到。 © 2022作者。

The development of novel anti-HER2 drugs opens new treatment options for women with breast cancers, including lower expression of HER2. The epidemiology and clinical outcome of metastatic HER2-low breast cancer remain not well described. We designed a retrospective cohort study of the 2010-2017 National Cancer Database (NCDB) was designed to compare the overall survival of HER2-low and HER2-zero de novo metastatic breast cancer with systemic therapy. Multivariable Cox regression models were performed to estimate hazard ratios (HR), adjusting for sociodemographic and clinical factors. A total of 20,636 of 30,929 (66.7%) patients were HER2-low and 10,293 (33.3%) were HER2-zero. When stratified by hormonal receptor status, HER2-low tumors account for 18,066 (69.7%) cases in HR+/HER2- population and 2570 (51.4%) cases in HR-/HER2- population. The prevalence of HER2-low tumors was similar across racial groups with a slightly lower prevalence among the Hispanic population. Women with HER2-low tumors had longer overall survival (OS) than women with Her2-zero tumors in both HR-positive (median OS 39.0 months vs. 37.1 months; adjusted HR: 0.95, 95%CI (0.91-0.98)) and HR-negative groups (median OS 15.8 months vs. 14.1 months; adjusted HR: 0.92 95%CI (0.86-0.98)). The survival advantage was primarily observed in patients who received chemotherapy as their first line of treatment (HR 0.92 95%CI (0.88-0.96) vs. 0.99 95%CI (0.94-1.04), p-interaction = 0.04). In summary, HER2-low tumors, irrespective of hormone receptor status, have better survival than HER2-zero tumors in the de-novo metastatic setting. The survival advantage was primarily observed in patients who received chemotherapy in the first line.© 2022. The Author(s).