Her-2-positive breast cancers are associated with higher recurrence rates and increased mortality. Trastuzumab, a humanised monoclonal antibody targeting the extracellular domain of Her-2, is an important part of palliative first-line therapy. Combination therapy with taxanes improved response rates, progression-free as well as overall survival.
Based on those results, different groups initiated prospective randomised phase III trials evaluating the role of trastuzumab in the adjuvant setting. Again, significantly superior outcomes were observed in terms of recurrence-free and overall survival. Importantly however, a recently presented French trial showed no additional benefit of trastuzumab over conventional chemotherapy alone. As the mentioned adjuvant studies had huge differences in their respective designs, a number of questions remain unanswered; furthermore, those differences may account for disparities in both, efficacy and side effects.
In the neo-adjuvant setting, the addition of trastuzumab to conventional chemotherapy yielded pathologic complete remission rates of up to 60%. Therefore, pre-operative therapy regimens of Her-2-positive tumours today should incorporate trastuzumab.
As reported from earlier studies, cardiotoxicity appears to be the most significant side effect of trastuzumab treatment; this apparently is most prominent if the antibody is administered closely to an anthracycline.
In this chapter, current knowledge of the role of trastuzumab in the adjuvant setting is discussed.