Changing Natural History of HER2–Positive Breast Cancer Metastatic to the Brain in the Era of New Targeted Therapies

BACKGROUND: Given the wide adoption of human epidermal growth factor receptor 2 (HER2)-targeted therapies for advanced HER2-positive breast cancer, we studied the natural history of patients with HER2-positive breast cancer brain metastases (BCBM) over time. PATIENTS AND METHODS: Patients with HER2-positive BCBM identified from a prospectively maintained database at the University of North Carolina were divided into 3 cohorts by year of BCBM diagnosis. Cohorts were selected by year of HER2-targeted therapy US Food and Drug Administration approval. Overall survival (OS), time to first metastasis, time to BCBM, and BCBM survival were estimated by the Kaplan-Meier method. Associations between OS after BCBM and clinical variables were assessed by Cox proportional hazards regression models. RESULTS: One hundred twenty-three patients were identified. Median age was 51 years, and 58% were white and 31% African American. OS from initial breast cancer diagnosis improved over time: 3.6 years (95% confidence interval CI, 2.8-6.1) in the 1998-2007 cohort, 6.6 years (95% CI, 4.5-8.6) in the 2008-2012 cohort, and 7.6 years (95% CI, 4.4-9.6) in the 2013-2015 cohort (P = .05). While time from initial diagnosis to first metastasis did not differ (P = .12), time to BCBM increased over time (2.6 years 95% CI, 1.3-3.5 for 1998-2007; 2.6 years 95% CI, 2.1-4.3 for 2008-2012, and 3.3 years 95% CI, 2.2-6 for 2013-2015; P = .05). Although OS from BCBM did not significantly differ by cohort, patients who received HER2-targeted therapy after BCBM had a prolonged OS (2.1 years 95% CI, 1.6-2.6 vs. 0.65 years 95% CI, 0.4-1.3; P = .001). CONCLUSION: OS from initial breast cancer diagnosis significantly improved over time for patients with HER2-positive breast cancer who develop BCBM, now exceeding 7 years; survival from BCBM diagnosis may now exceed 2 years.