New insights and emerging therapies for breast cancer brain metastases.
Breast cancer brain metastases (BCBMs) are the second most frequent secondary central nervous system metastases following those associated with non-small-cell lung cancer. It is increasingly evident that BCBM arises as a function of the biology of the primary tumor and the metastatic niche, which combine to create a unique microenvironment in the brain impacting both metastatic colonization and therapeutic response. Clinical outcomes are improving for BCBM patients as a result of modern combinatorial therapies, challenging the traditionally nihilistic approach to this patient subgroup. This review will focus on the breast cancer subtypes with the highest incidence of BCBM-human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and triple-negative (estrogen receptor [ER]-negative, progesterone receptor [PR]-negative, and HER2-negative) breast cancer (TNBC)-and will characterize differences in the clinical behavior of brain metastases that arise from these different subtypes. We will also highlight some of the recent preclinical studies that may shed light on the biological mechanisms and mediators underlying brain metastases. Finally, we will review published and current prospective trials of systemic therapies specifically for BCBM, including novel pathway-specific therapies.
Women's Cancers Program, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Elgene
E
Lim
Nancy U
NU
Lin
D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000556:secondary* / Q000628:therapy*; D001943:Breast Neoplasms / Q000473:pathology*; D000069287:Capecitabine; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D000077341:Lapatinib; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000627:therapeutic use; D010455:Peptides / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D016634:Radiosurgery; D011878:Radiotherapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D000068878:Trastuzumab
D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D000077341:Lapatinib; D017239:Paclitaxel; D010455:Peptides; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C531859:paclitaxel-Angiopep-2 conjugate