PROGNOSTIC FACTORS OF HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2- POSITIVE (HER2+) BREAST CANCER PATIENTS WITH BRAIN METASTASIS IN THE ERA OF TARGETED THERAPY

Introduction: Patients with advanced human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) frequently experience brain metastases (BM), which are associated with poor prognosis and thus excluded from most clinical studies. The advent of HER2-directed therapy resulted in improved survival outcomes, and how managing HER2+ BCBM is a challenge for the oncologist. Objective: Determine the clinicopathologic factors associated with the prognosis of patients with HER2+ BCBM, in the scenario of anti-HER2 therapies. Methods: This is an unicenter, retrospective analysis of patients diagnosed with HER2+ BCBM between March 2005 and January 2018 . Statistical analysis were conducted with SPSS V.23 using Kaplan-Meier method and Cox regression analysis. Results: 97 patients with HER2+ BCBM were included, median age was 50 years old, 31% had stage IV and 16% presented with BM at diagnosis . At the time of the diagnosis of the first BM, 50 (74,6%) patients presented with neurological symptom . Median time from primary BC to BM was 30,9 months. The median survival after developing BM was 28,9 months. Patients with more than 3 BM had significantly shorter overall survival (p = 0,01). 21patients (21,6%) underwent surgical treatment of metastasis in the brain and there was association with survival duration (p = 0,02). Patients treated with radiotherapy (60,9%) had significantly better survival (p = 0,03). Treatment with HER2-targeting agents after BCMB had significantly increased survival (p = 0,022). On multivariate analysis for OS, the presence of more than 3 BM (p = 0,02) and non use of HER2-targeting agents after BCMB (p = 0,01) were independent prognostic factors. Patients with health ensurance showed a median OS of 30 months vs. 14 months for for public health patients (p = 0.20). Conclusion: Our study indicates that HER2+ BC patients with more than 3 BM and treatment without use of HER2-targeting agents after BCMB have a poor prognosis. The best treatment strategy is not yet known and the study of prognostic factors may help to choose a better treatment sequence. In this analysis, the patients with health ensurance presented double the overall survival in relation to public health. These data suggest that differences in access to optimal treatment may play an important role in the management of these patients.