Abstract P3-12-12: Chemotherapy and targeted therapy after whole-brain radiotherapy may improve survival in RPA class II/III patients with brain metastases from breast cancer

Abstract

Abstract Background: Brain metastases (BM) represent an important cause of morbidity and mortality from breast cancer (BC). Whole brain radiotherapy (WBRT) remains the most widely used treatment, especially for pts with multiple intracranial lesions. The purpose of this study is first, to analyze the clinical characteristics of BM with molecular subtypes, then, to evaluate the role of systemic treatment after WBRT in pts with different recursive partitioning analysis (RPA) of RTOG. Methods: A total of 101 pts with BM from BC treated with WBRT in single institution between the Jan.2006 and Nov. 2010 were retrospectively analyzed. All patients were divided into four biological subgroups based on the levels of estrogen, progesterone and human epidermal growth factor receptor 2(HER2) receptors. Prognostic analysis was performed including age at BM, KPS/RPA, number of BM, interval between BC diagnosis and BM, presence of extracranial metastases, primary tumor control, molecular subtype of primary cancer, systemic treatment after WBRT and total dose of radiotherapy. Results: In univariate analysis, age, KPS/RPA classes, number of BM, primary tumor control, extracranial metastases and systemic treatment after WBRT were significant prognostic factors for overall survival (OS) (p < 0.05), while in multivariate analysis, KPS/RPA classes and systemic treatment after WBRT were the only significant prognostic factors for OS. No impact of radiation doses on OS was found. The median survival for the whole group was 12 m, which was 16 and 5 m respectively (p = 0.001) in pts with and without systemic treatment after WBRT, 20 and 5 m in pts with and without chemotherapy (p = 0.001). In HER-2 positive pts, median survival with and without post-WBRT target therapy was 34 and 8 m respectively (p = 0.001). Endocrine therapy did not improve survival in ER and/or PR positive pts, (median 14 vs 20 m, p = 0.437). In the entire group, median survival in RPA classes I, II and III was 24, 18 and 3 m, respectively (p < 0.001). In RPA class I, median survival with and without systemic treatment after WBRT was 25 and 22 m respectively (p = 0.819), while in RPA class II/III, systemic treatment improved survival from 7 and 2 m to 11 and 5 m respectively (p < 0.05). The proportion of pts with luminal A, luminal B, HER2-positive and triple negative was 28 (27.7%), 18 (17.8%), 17 (16.8%) and 38 (37.6%), respectively. 47.4% triple negative subtype pts develop brain metastasis as the first metastatic site while only 25.4% the other subtypes pts metastasize to brain firstly (p = 0.03). The median interval between BC diagnosis and the time of BM was shorter in the triple negative pts compared to luminal A subtype (26 vs.36 m, p = 0.021). Conclusions: Triple negative pts are more likely to metastasize to the brain and tend to have shorter interval from initial diagnosis to the development of BM compared to luminal A pts. KPS remains an important prognostic factor for pts with BM from BC. Systemic treatment after WBRT could improve survival in RPA class II/III pts, especially chemotherapy and targeted therapy. Thus, it is recommended to continue tailored systemic therapy after WBRT. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-12-12.