title: A systematic review of trastuzumab and lapatinib in the treatment of women with brain metastases from HER2-positive breast cancer.
abstract: Patients with HER2-positive breast cancer are living still longer and increasingly experiencing brain metastases. Current HER2-targeted therapies have limited potential to cross the blood-brain-barrier. We performed a systematic review to investigate data on HER2-targeting therapies in the treatment of brain metastases in breast cancer. We searched PUBMED for all human studies published 1998-2012 using the following search terms: breast neoplasm/cancer, human epidermal growth factor receptor 2/HER2, ErbB2, trastuzumab, lapatinib, brain/cerebral neoplasm/metastases and blood-brain barrier. We identified few and mostly small clinical studies. Study designs were very heterogeneous making comparisons on endpoints difficult. Overall survival for patients treated with trastuzumab varied from 8 to 25 months and 5.5 to 11 months for patients receiving lapatinib. The majority of studies were retrospective thus possibly biasing data. Only three studies were identified comparing trastuzumab to lapatinib. Conclusively, no solid data exist on how to treat patients with HER2-positive disease and brain metastases. Although continuous HER2-blockade is recommended by international consensus guidelines, it is still not evident which HER2-targeting agent should be preferred when brain metastases occur. The choice of chemotherapy to accompany the blockade is not obvious and we do not know if dual is better than single blockade. Further clinical trials are urgently needed.
authors.affiliation: Department of Oncology, Herlev Hospital, University of Copenhagen, Denmark. frk.pia.larsen@gmail.com
authors.forename: Pia Bükmann
authors.initials: PB
authors.lastname: Larsen
authors.forename: Iben
authors.initials: I
authors.lastname: Kümler
authors.forename: Dorte Lisbet
authors.initials: DL
authors.lastname: Nielsen
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D011799:Quinazolines / Q000008:administration & dosage / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab
keywords: ASCO; American Society of Clinical Oncology; BBB; BM; Brain metastases; CNS; CR; ECOG; Eastern Cooperative Oncology Group; FDA; Food and Drug Administration; HER; Lapatinib; MBC; Metastatic breast cancer; OS; PFS; PR; PS; SD; TTP; Trastuzumab; WBRT; blood brain barrier; brain metastases; central nervous system; complete response; human epidermal growth factor receptor; metastatic breast cancer; overall survival; partial response; performance status; progression free survival; stable disease; time to progression; whole brain radiation therapy