title: Integrating trastuzumab in the neoadjuvant treatment of primary breast cancer: accumulating evidence of efficacy, synergy and safety.
abstract: Neoadjuvant chemotherapy is used in non-metastatic breast cancer in order to eradicate micrometastatic deposits early during disease course, as well as in order to decrease tumour bulk and render surgery feasible or breast-conserving. Moreover, it offers promise to serve as an in vivo chemosensitivity assay and as a powerful predictive factor for outcome. Trastuzumab, a monoclonal antibody targeting an epitope in the extracellular domain of the Human Epidermal Growth Factor Receptor-2 (HER2/erbB-2), was found to be active in HER2-overexpressing metastatic as well as in resected breast cancer when given post-operatively. In this review, we summarise the evidence on the activity and safety of trastuzumab-containing neoadjuvant chemotherapy for the management of women with localised, irresectable or resectable breast cancer. Twenty-three published studies enrolling a total of 585 patients reported pathologic complete responses (pCR) ranging from 7 to 78% with a favourable adverse event profile, data that are presented and discussed in this review. The impact of trastuzumab on long-term outcome, the identification of surrogate biomarkers for sensitivity or resistance to antineoplastic therapy, the optimal schedule of trastuzumab administration and the more active chemotherapeutic regimen for synergism are only a few of the key points needing elucidation so as to rationalise trastuzumab-based approaches.
authors.affiliation: Department of Medical Oncology, Ioannina University Hospital, Niarxou Avenue, 45500 Ioannina, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Lazaridis
authors.forename: George
authors.initials: G
authors.lastname: Pentheroudakis
authors.forename: Nicholas
authors.initials: N
authors.lastname: Pavlidis
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D004357:Drug Synergism; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human