Characteristics and Prognostic Factors for Patients With HER2-overexpressing Breast Cancer and Brain Metastases in the Era of HER2-targeted Therapy: An Argument for Earlier Detection

A retrospective cohort study of one hundred HER2-positive breast cancer patients with brain metastases (BM) was conducted to examine the clinical characteristics and outcome in the era of HER2-targeted therapy. The factors associated with survival included: performance status, number of BM, non-CNS disease control, anti-HER2 therapy use after the BM diagnosis, and presence of neurological symptoms. Background: Although brain metastases (BM) are associated with poor prognosis, patients with human epidermal growth factor receptor 2 (HER2) overexpressing (HER2 ⁺ ) breast cancer (BC) with BM who are treated with anti-HER2 therapy have a relatively longer survival after BM diagnosis compared with other subtypes and HER2 ⁺ patients previously untreated with anti-HER2 therapy. It is unclear if previously reported prognostic factors are applicable to patients with HER2 ⁺ BC in the era of HER2-targeted therapy. Patients and Methods: We evaluated 100 consecutive patients with HER2 ⁺ BC with BM who underwent radiation therapy as primary BM treatment from January 2001 to December 2011 at Memorial Sloan Kettering Cancer Center by retrospective review. Patient characteristics at the time of BM diagnosis and their associations with time from BM to death were evaluated by Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models. Results: Significantly better survival from BM was noted for patients with higher performance status, fewer BM lesions, continued use of HER2-targeted therapy after BM diagnosis, and better controlled extracranial metastatic disease. Absence of neurologic symptoms at BM diagnosis was significantly associated with fewer lesions, decreased use of whole brain radiotherapy, and longer survival in univariate and multivariate analysis (multivariate hazard ratio, 3.69; 95% confidence interval, 1.69-8.07). Conclusion: Our finding supports the continued use of HER2-targeted therapy after BM diagnosis. In addition, future research on the clinical impact of detecting asymptomatic BM in patients with HER2 ⁺ BC, in terms of improving prognosis, quality of life, and avoidance of whole brain radiotherapy, is warranted.