Understanding patterns of brain metastasis in breast cancer and designing rational therapeutic strategies

One of the most feared sequelae after a diagnosis of advanced breast cancer is development of metastases to the brain as this diagnosis can affect physical function, independence, relationships, quality of life, personality, and ultimately one's sense of self. The propensity to develop breast cancer brain metastases (BCBMs) varies by subtype, occurring in up to one half of those with triple negative breast cancer (TNBC), approximately a third of HER+ breast cancers and 14% in hormone positive disease. Median survival after BCBM diagnosis can be as short as 5 months in TNBC and 10-18 months in the other subtypes. Here, we review the biology of BCBMs and how it informs the rational design of new therapeutic approaches and agents. We discuss application of novel targeted and immunotherapies by breast cancer subtype. It is noteworthy that there are no U.S. Food and Drug Administration (FDA)-approved treatments specifically for BCBMs currently. Nevertheless, there are legitimate grounds for hope as patients with BCBMs are now being included in clinical trials of systemic therapies and a better understanding of the biology and genetic underpinning of BCBMs is driving an increased range of options for patients.