Anti-human epidermal growth factor receptor 2 monoclonal antibody therapy for breast cancer.
BACKGROUND
Advances in molecular biology and improved understanding of tumour biology have led to the development of novel treatments for cancer. Trastuzumab (Herceptin; Genentech, San Francisco, California, USA) is a monoclonal antibody directed against human epidermal growth factor receptor (HER) 2 protein, which is overexpressed in a wide variety of human cancers, including 20-30 per cent of human breast cancers. HER-2 plays an important role in oncogenic transformation, tumorigenesis and metastatic spread. Overexpression is associated with a poor prognosis and predicts a poor response to several treatment modalities.


METHODS
Literature relating to the monoclonal antibody was identified by a Medline literature search and by cross-referencing from the references of seminal articles on the subject. Four major clinical trials were identified and reviewed.


CONCLUSIONS
In clinical trials approximately 15-20 per cent of patients with HER-2-overexpressing tumours benefited from treatment with trastuzumab. In sensitive patients the antibody appeared to have intrinsic anticancer activity when given as a single agent. In combination chemotherapy it appeared to act synergistically with other agents. Ongoing research is evaluating trastuzumab in combination with numerous standard chemotherapy regimens and with other novel chemotherapeutic agents. Clinical trials have also revealed several serious side-effects of monoclonal antibody therapy. Most notable is an unpredictable cardiotoxicity, especially when used in combination with anthracycline-based chemotherapy regimens.
Leonard
D S
DS
Department of Surgery, St Vincent's University Hospital, University College Dublin, Elm Park, Dublin 4, Ireland.
Hill
A D K
AD
Kelly
L
L
Dijkstra
B
B
McDermott
E
E
O'Higgins
N J
NJ
D018943:Anthracyclines / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007376:Interleukin-2 / Q000008:administration & dosage; D015337:Multicenter Studies as Topic; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D000068878:Trastuzumab
D018943:Anthracyclines; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002945:Cisplatin; D003520:Cyclophosphamide; D007376:Interleukin-2; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab