Predictors of time to brain metastasis and survival in patients diagnosed with breast cancer.
Authors: Hijazi Ali , Mohanna Mohamed , Sabbagh Saad , Herran Maria , Guleryuz saffet , Dominguez Barbara , Nahleh Zeina A. 
Published: July 2024

e13122

Background: Patients with breast cancer (BC) who develop brain metastases (BM) have poor survival outcomes. We aimed to identify significant predictors of time to develop BM and survival after diagnosis. Methods: Patient records were retrospectively reviewed from the Cleveland Clinic database between 2010-2020. Patients with a BC and a BM diagnosis were included for analysis. One way ANOVA was used to compare mean time to BM across subgroups (mean ± SE), and Kaplan-Meier method was used to compute median overall survival (mOS) after BM diagnosis (95% CI). Results: N=109 patients were included in the analysis with a mean age of 52 ± 13 years, mean time to developing BM of 42 ± 35 months, and mOS after BM of 12.00 months (8.99-15.01). The patients’ characteristics were as follows: female (98.2%), white (83.5%), married (56%), privately insured (43.1%), had a Karnofsky Performance Status (KPS) >80 (61.7%), and 21% had stage IV at initial diagnosis. In terms of BC characteristics, 80.4% of cases were ductal, 63.7% were Grade III, 52.3% were HR+, and 31.5% were HER2+, and 32.4% were triple negative. Most patients had extracranial metastases (ECM) at the time of BM diagnosis (67.8%), had at least 2 sites of BM (71.6%), parenchymal only BM (75%), and 10-30 mm BM (44.2%). 15.8% of patients underwent craniotomy and 86.2% received at least one form of radiotherapy (RT) for BM. The HR+/HER2- group had the longest time to BM compared to the shortest in the triple negative group (61.29 ± 6.95 vs 28.59 months ± 4.80, p<0.001). Patients receiving hormonal therapy had longer time to BM compared to those who didn’t (50.83 ± 5.04 vs 35.98 ± 4.67 months, p=0.034). Patients with Stage I disease had the longest time to develop BM (68.50 ± 13.66 months, p=0.009), while grade III status had the shortest time to BM (34.46 ± 3.46 months, p=0.002). Uninsured patients had the shortest time to BM (22.92 ± 4.09 months, p=0.003). After BM diagnosis, the HR+/HER2+ group achieved the best mOS at 35.00 months (14.20-55.80, p=0.040). Patients receiving Gamma Knife Radiosurgery (GKRS) achieved longer mOS than the other RT modalities at 30.00 months (11.46-48.51) vs 20.00 (1.26-38.74) in GKRS + Whole Brain RT (WBRT), 9.00 (3.43-14.57) in the WBRT, and 2.00 (1.12-2.88) in no RT group (p=0.022). Patients with a KPS of <80 had a shorter mOS compared to those with a KPS of >80 [5.00 (2.02-7.98) vs 17.00 (9.41-24.6), p=0.002]. Patients receiving hormonal therapy had longer mOS compared to those who did not [17.00 (6.58-27.43) vs 9.00 (3.72-14.28), p=0.016]. Patients with stage I disease had longer mOS compared to those with stage II-IV disease [41.00 (22.70-59.30) vs 10.00 (6.60-13.40), p=0.025]. Conclusions: This study identifies significant clinical predictors for BM development and survival in patients with BC including Hormone receptor status, treatment modalities, stage, and KPS. These findings emphasize the need for early BM screening in high-risk patients to improve survival.