Breast cancer patients with brain metastases or leptomeningeal disease: 10-year results of a national cohort with validation of prognostic indexes

Abstract

Development of brain metastasis (BM) and leptomeningeal (LM) disease in breast cancer (BC) patients indicates poor prognosis and impairs patients' quality of life. Prognostic survival scores for BM can help predict expected survival in order to choose the most appropriate treatment. The aim of our study was to analyze national data for BC patients treated with radiation therapy for BM/LM disease and validate the applicability of different survival prognostic scores. We retrospectively evaluated medical records of 423 BC patients with BM/LM disease receiving radiation therapy between April 2005 and December 2015. Patients were classified by BC Recursive Partitioning Analysis (B-RPA), Breast Graded Prognostic Assessment (Breast-GPA), Modified Breast Graded Prognostic Assessment (MB-GPA), and Simple Survival score for patients with BM from BC (SS-BM). Overall survival (OS) was calculated from the development of BM/LM disease to death or last follow-up date. After a median follow-up of 7.5 years, the median OS was 6.9 months (95% CI 5.5-7.8, range 0-146.4) and 1- and 2-year survival rates were 35% and 17%, respectively. Survival analysis showed significant differences in median OS regarding biologic subtypes (P < 0.0001), as follows: 3.2 (95% Confidence Interval (CI) 2.5-3.9), 3.9 (95% CI 2.3-5.6), 7.1 (95% CI 4.3-9.8), 12.1 (95% CI 8.3-15.9), and 15.4 (95% CI 8.8-22.1) months for primary triple-negative BC (TNBC), Luminal B HER2-negative, Luminal A, HER2-enriched, and Luminal B HER2-positive tumors, respectively. Good Karnofsky Performance Status (KPS), single metastasis, and absence of LM or extracranial disease all demonstrated better OS in univariate and multivariate analysis. All four employed prognostic indexes provided good prognostic value in predicting survival. SS-BM and MB-GPA showed the best discriminating ability (Concordance indexes C were 0.768 and 0.738, respectively). This study presents one of the largest single-institution series validating prognostic scores for BC patients with BM/LM. SS-BM and MB-GPA proved to be useful tools in the clinical decision-making process.

Keywords: brain metastases; breast cancer; prognostic score; radiation therapy; survival prognosis.