Genomics of breast cancer brain metastases: a meta-analysis and therapeutic implications

Abstract

Abstract Background Breast cancer brain metastases are challenging daily pratice, and the biological link between gene mutations and metastatic spread to the brain remains to be determined. Here, we performed a meta-analysis on genomic data obtained from primary tumors, extracerebral metastases and brain metastases, to identify gene alterations associated with metastatic processes in the brain. Methods Articles with relevant findings were selected using Medline via PubMed, from January 1999 up to February 2022, and the algorithms were the following: ("Breast Neoplasms"[Mesh] AND "metast*" AND ("Genomics"[Mesh] OR "mutation*")), and "Breast" AND "brain" AND "metast*" AND ("Genom*" OR "mutation*" OR "sequenc*"). A critical review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement (PRISMA). Results Fifty-seven publications were selected for this meta-analysis, including 37,218 patients in all, 11,906 primary tumor samples, 5,541 extracerebral metastasis samples, and 1,485 brain metastasis samples. We report overall and sub-group prevalence of gene mutations, including comparisons between primary tumors, extracerebral metastases and brain metastases. In particular, we identified 6 genes with a higher mutation prevalence in brain metastases than in extracerebral metastases, with a potential role in metastatic processes in the brain: ESR1, ERBB2, EGFR, PTEN, BRCA2 and NOTCH1. We discuss here the therapeutic implications. Conclusion Our results underline the added value of obtaining biopsies from brain metastases to fully explore their biology, to develop personalized treatments.