Real-world outcomes of breast cancer patients with brain metastases treated with radiotherapy in Ontario: A population-based study.
Authors: Jerzak Katarzyna Joanna , Rosen Michael , Wang Xin Y , Chehade Rania , Zhang Bo , Saskin Refik , Das Sunit , Soliman Hany , Sahgal Arjun , Chan Kelvin K. 
Published: June 2021

2027 Background: Brain Metastases (BrM) are a major cause of morbidity and mortality in patients with metastatic breast cancer (MBC). Real-word data regarding time to development of breast cancer BrM and survival outcomes is lacking. Methods: We conducted a retrospective, observational population-based cohort study to assess treatment patterns and outcomes of patients with de-novo MBC who received radiotherapy for intracranial metastatic disease between January 2009 and December 2018. We used population health administrative databases in Ontario held at ICES, an independent, non-profit research institute. Primary endpoints were i) cumulative incidence of radiotherapy for BrM accounting for the competing risk of death, and ii) time from MBC diagnosis to brain radiotherapy. Secondary endpoints included overall survival (OS) and radiation therapy toxicity. Data were censored if patients were alive on the same therapy at last available follow-up with the last cut-off date being March 31, 2019. Kaplan-Meier analyses were performed for the time to event endpoints and compared using the log-rank test. Cumulative incidence of radiotherapy for BrM from the diagnosis of MBC was calculated using the Cumulative Incidence Function (CIF), accounting for the competing risk of death using a competing risk analysis. Multivariable regression models were used to account for confounding variables. Results: 3,916 patients with de-novo MBC were identified, among whom 549 (14%) developed BrM requiring radiotherapy; cumulative incidence of BrM at 7-year follow-up was highest among patients with HER2+/HR- (34.7%) and HER2+/HR+ (28.1%) disease, followed by triple negative MBC (21.9%) and HR+/HER2- (12.1%) subtypes. The median time from diagnosis of MBC to first radiotherapy treatment for BrM was 7.5 months, 15.0 months, 16.8 months and 19.8 months, in TNBC, HER2+/HR-, HR+/HER2- and HER2+/HR+ subtypes, respectively. The median OS from radiotherapy among patients with breast cancer BrM was 5.1 months in the overall cohort. When analyzed by subtype, the median OS was 2.6 months, 4.8 months, 8.7 months, and 9.4 months in TNBC, HR+/HER2, HER2+/HR+ and HER2+/HR- subtypes, respectively. In a multivariable Cox regression model, a triple negative or HR+/HER2- breast cancer subtype, treatment with WBRT, age > 60 and a high-income quintile (4 or 5) were independently prognostic for shorter OS after adjustment for the index year at diagnosis. Patients treated with stereotactic radiosurgery (SRS) had lower 30-day mortality (6.4% vs. 18.9%, p = 0.003) and lower likelihood of hospitalization within 30 days of therapy (9.6% vs. 20.2%, p = 0.015) compared to patients treated with WBRT. Conclusions: Approximately 1 in 7 patients with MBC will require radiotherapy for BrM. Our data support the use of SRS when clinically indicated and provide insights regarding the time to development of BrM by breast cancer subtype.