[Use of trastuzumab in the therapy of breast cancer].
Trastuzumab (Herceptin) is a humanized monoclonal antibody recognizing the human epidermal growth factor receptor-2 (HER-2/neu). This receptor is overexpressed in 20-30% of invasive breast carcinomas. HER-2/neu normally regulates cell growth and survival, and overexpression leads to increased signaling and thus to malignant transformation and growth. HER-2/neu overexpression used to confer a worse prognosis, as these tumors respond poorly to a variety of chemo- and hormonal therapies. The invention of targeted therapies against the HER-2/neu receptor changed this picture. Trastuzumab binds to HER-2/neu close to the cell membrane and inhibits signal transduction, as well as leading to receptor degradation and immune-mediated attack against the tumor cells. It was shown to be effective and safe in several clinical trials, and approved for use in humans. The most important adverse effect is cardiotoxicity, leading to a risk of congestive heart failure in some patients, especially those pretreated with anthracyclines. As this risk is low, adjuvant trastuzumab therapy was investigated and showed very positive results. The addition of trastuzumab to adjuvant chemotherapy consistently resulted in significant increases of both disease-free and overall survival. Therefore, trastuzumab should nowadays be applied to all eligible patients, i.e. patients whose tumor over-expresses HER-2/neu with a immunostaining intensity of 3+ or shows HER-2/neu gene amplification as demonstrated by fluorescence in situ hybridization (FISH), and who do not have other contraindications. This article highlights the results of pertinent clinical trials and discusses current knowledge on the optimal use of trastuzumab.
Riemer
Angelika B
AB
Klinische Abteilung für Onkologie, Universitätsklinik für Innere Medizin I, Medizinische Universität Wien, Währinger Gürtel 18-20, Vienna.
Zielinski
Christoph C
CC
D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D010166:Palliative Care; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human