Clinical outcomes of de novo metastatic HER2-low breast cancer: a National Cancer Database Analysis.

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.