Survival and disease control after upfront stereotactic radiosurgery for brain metastases from breast cancer.
Authors: Wang Yan , An Ran , Wang Fuchenchu , Singareeka Raghavendra Akshara , Gao Chao , Kim Yon Son Betty , Briere Tina Marie , Amaya Diana , Li Jing 
Published: June 2021

e14013

Background: As systemic therapy for metastatic breast cancer (BC) improves, effective treatment for central nervous system involvement has become a major concern, as 10%‒30% of such patients develop brain metastases (BMs). The survival benefit from hormonal and targeted therapy urges to treat patients with BMs with minimal toxicity and less systemic interruption. Here we assessed survival and disease control in patients who received upfront stereotactic radiosurgery (SRS). Methods: We retrospectively reviewed 236 patients who received upfront SRS with/without surgery for BMs from metastatic BC at a single large-volume cancer center from June 2007 to May 2018. We excluded patients who received SRS for surgical cavity alone. A total of 212 were evaluable, of whom 68 had triple-negative (TN), 66 HR+/HER2-, 46 HR+/HER2+, and 32 HER2+ molecular subtypes. Primary endpoints were overall survival (OS) from BM diagnosis and salvage radiation free survival (SRTFS), which were estimated by Kaplan-Meier survival analysis. Cox proportional hazard regression analysis was used to identify prognostic factors. Results: Median age at BM diagnosis was 52.5 y (range 25.6‒85.4); median Karnofsky Performance Score (KPS) was 90 (range 60‒100); and median number of BMs treated was 2 (range 1‒17). At a median follow-up time of 15.4 months (mo) (range, 0.8–119.6), the estimated median OS was 18.5 mo (95% CI, 14.9–21). Factors associated with OS on multivariate analysis (MVA) were subtype (12.2 mo for TN, 13.3 mo for HR+/HER2-, 36.4 mo for HR+/HER2+, and 28.1 mo for HER2+, p= 0.002), KPS ( p <0.0001), receipt of chemotherapy ( p= 0.016) or anti HER2+ therapy (0.029) after diagnosis of BM, and type of salvage radiation ( p <0.0001). Age, extracranial disease status at BM diagnosis, or receipt of upfront surgery was not associated with OS. OS was also comparable in patients who received upfront SRS to less or more than 4 lesions (19.3 mo for < 4 [n = 162] vs. 17.8 mo for > / = 4 [n = 50], p= 0.36). Of the 106 patients (50%) who received salvage therapy after initial SRS, 42 received salvage SRS, 28 received salvage whole-brain radiation therapy (WBRT), and 36 received both. The 12-month salvage RT rate was 25% for WBRT and 26.4% for SRS. The median SRTFS was 7.4 mo (95% CI, 6.5‒8.3). Factors associated with SRTFS on MVA were subtype ( p= 0.002), KPS ( p= 0.011), and receipt of Hormone therapy after a diagnosis of BM (p = 0.031). Conclusions: Molecular subtypes of HER2+ and HR+/HER2+, good KPS, and receipt of chemotherapy or anti-HER2 therapy predicted better OS for patients who received upfront SRS for BMs from BC. Number of BMs treated by upfront SRS was not associated with OS. Molecular subtype, KPS, and receipt of Hormone therapy were also associated with SRTFS. Prospective studies are needed to clarify the best treatment strategies for the various subgroups of patients with BMs from BC particularly in the era of increasing use of new systemic therapies.