Purpose: This study aims to conduct a systematic review of the literature to identify biomarkers associated with breast cancer brain metastasis (BCBM).
Methods: A systematic search was conducted in PubMed, Embase, Web of Science, and Cochrane for relevant literature up until October 1, 2018. Case reports, conference abstracts, and expert opinions/letters were excluded. Studies were included if they investigated risk factors for BCBM in a cohort of patients with locoregional or metastatic breast cancer of any subtype.
Results: From the 4866 studies that were screened, 117 were selected for inclusion and review. Twenty-eight unique biomarkers were investigated, of which three (EGFR, Ki-67, and p53) were assessed by more than two authors. In a pooled analysis of 3 studies, EGFR expression was associated with an increased risk of BM (RR 3.48, 95% CI 2.27-5.32, I2=0%, p-interaction = 0.39, n= 571 patients). In a pooled analysis of 5 studies, increased Ki-67 expression was associated with an increased risk of BM (RR 2.91, 95% CI 1.96-4.32, I2=59%, p-interaction = 0.05, n= 1,178). In a pooled analysis of 4 studies, p53 expression was not associated with a statistically significant risk of BM (RR 1.42, 95% CI 0.98-2.06, I2=53%, p-interaction = 0.10, n= 738).
Conclusions: This study summarizes the various biomarkers investigated for a role in breast cancer brain metastasis. Two biomarkers, EGFR and Ki-67 were identified as having a statistically significant increased risk of BCBM while p53 was not found to be statistically significant. Future studies are needed to develop more robust prediction models, as well as evaluate the other biomarkers identified in this study, which could help clinicians identify patients at high risk of breast cancer brain metastasis.