Real-World Study Assessing Characteristics and Treatment Patterns of Patients With Human Epidermal Growth Factor Receptor 2 Immunohistochemistry 0 and Human Epidermal Growth Factor Receptor 2–Low Stage IV Breast Cancer: A Multicenter Retrospective Study

PURPOSE To describe and compare patient characteristics, treatment patterns, and survival outcomes of patients with human epidermal growth factor receptor 2 (HER2)–low and HER2 immunohistochemistry 0 (IHC 0) stage IV breast cancer METHODS A retrospective study was conducted across three academic centers in the United States. Adult patients diagnosed with stage IV breast cancer between 1-1-2010 and 12-31-2020 and classified as having either HER2-low (immunohistochemistry 1+/2+ with negative fluorescence in situ hybridization) or HER2 IHC 0 disease were followed through 12-31-2021. Patient characteristics, treatments received, and treatment discontinuation were analyzed and survival analyses were conducted using Kaplan-Meier methods. RESULTS Among 501 eligible patients, 385 were classified as HER2-low (76.8%) and 116 as HER2 IHC 0 (23.2%). No statistically significant differences were found for demographic characteristics, but PTEN mutations (11.6% v 0%, P = .02) were more common, while germline BRCA1 mutations (1.9% v 8.6%, P = .04) were less prevalent in the HER2-low subgroup compared with those with HER2 IHC 0 disease. Treatment patterns in both subgroups were largely similar. In the overall cohort, 20%-30% of patients who discontinued treatment did not proceed to a subsequent line of therapy. Median overall survival trended shorter in the HER2 IHC 0 subgroup than the HER2-low subgroup, but 95% confidence intervals overlapped. For both subgroups, progression-free survival (PFS) decreased substantially at 2L and 3L compared with previous line of therapy. CONCLUSION Patient characteristics were similar between HER2-low and HER2 IHC 0 subgroups except for some differences in genetic alterations. Deterioration of PFS in later lines of therapy highlights a potential unmet need. Given the high patient attrition, the most effective treatments should be used as early as indicated as some patients may not proceed to subsequent lines of therapy.