In the past, the standard of care for treatment of BM was whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), and surgery. There has been a greater role for medical therapies in the last two decades due to the discovery of driver mutations and corresponding targeted therapies. These innovations have dramatically altered the approach to treating these patients. Some of the important mutations include epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations in small cell lung cancer, human epidermal growth factor receptor (HER2) mutation in breast cancer, and BRAF mutation in melanoma. Disease-specific graded prognostic assessments have identified prognostic factors for each of the major tumor types associated with BM. These reflect the increased treatment sensitivity of these tumors to specific agents. Furthermore, there is a difference in the genetic makeup of BM compared to their primary tumor. Genomic studies of BM patients comparing somatic point mutations and copy number variations with their primary tumor have demonstrated that while both the primary tumor and BM share a number of common mutations, BM can often develop distinct mutations. Therefore, there is a need to individualize systemic therapies in BM. Several organizations including the Food and Drug Administration and the American Society of Clinical Oncology now emphasize the inclusion of BM patients in various phases of clinical drug development.
Keywords: Brain metastases; Breast cancer; Checkpoint inhibitors; HER2; Lapatinib; Neratinib; Stereotactic radiosurgery; Targeted agents; Trastuzumab; WBRT.