Central Nervous System Metastasis in Patients With HER2-Positive Metastatic Breast Cancer: Patient Characteristics, Treatment, and Survival From SystHERs

Background Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) with central nervous system (CNS) metastasis have a poor prognosis. We report treatments and outcomes in patients with HER2-positive MBC and CNS metastasis from the Systemic Therapies for HER2-positive Metastatic Breast Cancer Study (SystHERs). Methods SystHERs (NCT01615068) was a prospective, US-based, observational registry of patients with newly diagnosed HER2-positive MBC. Study endpoints included treatment patterns, clinical outcomes, and patient-reported outcomes (PROs). Results Among 977 eligible patients enrolled (2012-2016), CNS metastasis was observed in 87 (8.9%) at initial MBC diagnosis and 212 (21.7%) after diagnosis, and was not observed in 678 (69.4%) patients. White and younger patients, and those with recurrent MBC and hormone receptor-negative disease, had higher risk of CNS metastasis. Patients with CNS metastasis at diagnosis received first-line lapatinib more commonly (23.0% vs. 2.5%), and trastuzumab less commonly (70.1% vs. 92.8%), than patients without CNS metastasis at diagnosis. Risk of death was higher with CNS metastasis observed at or after diagnosis (median overall survival [OS] 30.2 and 38.3 months from MBC diagnosis, respectively) versus no CNS metastasis (median OS not estimable; hazard ratio 2.86 [95% confidence interval 2.05-4.00] and 1.94 [95% confidence interval 1.52-2.49]). Patients with versus without CNS metastasis at diagnosis had lower quality of life at enrollment. Conclusions Despite advances in HER2-targeted treatments, patients with CNS metastasis continue to have a poor prognosis and impaired quality of life. Observation of CNS metastasis appears to influence HER2-targeted treatment choice.

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