Integrating trastuzumab in the neoadjuvant treatment of primary breast cancer: Accumulating evidence of efficacy, synergy and safety

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.