title: Targeted Therapies for Brain Metastases from Breast Cancer.
abstract: The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor, mechanistic target of rapamycin (mTOR) pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6) pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease. Approximately 20%-30% of patients with metastatic breast cancer develop brain metastases. Surgery, whole brain radiation therapy, and stereotactic radiosurgery are the traditional treatment options for patients with brain metastases. The therapeutic paradigm is changing due to better understanding of the blood brain barrier and the advent of tyrosine kinase inhibitors and monoclonal antibodies. Several of these agents are in clinical practice and several others are in early stage clinical trials. In this article, we will review the common targetable pathways in the management of breast cancer patients with brain metastases, and the current state of the clinical development of drugs against these pathways.
authors.affiliation: Division of Hematology, Oncology, Blood and Bone Marrow Transplantation, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. vyshak-alvavenur@uiowa.edu.
authors.forename: Vyshak Alva
authors.initials: VA
authors.lastname: Venur
authors.affiliation: Division of Hematology, Oncology, Blood and Bone Marrow Transplantation, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. jose-leone@uiowa.edu.
authors.forename: José Pablo
authors.initials: JP
authors.lastname: Leone
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors
keywords: CDK-4/6; EGFR; HER2; PI3K; VEGF; brain metastases; breast cancer; mTOR