Abstract

Trastuzumab in the adjuvant setting: a practical review

Author(s): Valentina Rossi, Stefania Redana, Andrea Milani, Elena Geuna, Giorgio Valabrega, Massimo Aglietta and Filippo Montemurro

Trastuzumab is a monoclonal antibody directed against the product of the HER2/neu oncogene. The HER2 protein is overexpressed in approximately 20% of human breast cancers and is associated with adverse prognosis. Randomized studies in patients with HER2-positive advanced breast cancer demonstrated an increased response rate and survival when trastuzumab was added to chemotherapy. These results prompted the conduction of several large trials with trastuzumab in the adjuvant setting. Approximately 16,000 women with HER2-positive early breast cancer have been randomized in trials assessing the efficacy of trastuzumab added to adjuvant chemotherapy. All of these trials, except one, have confirmed superior outcomes of the experimental trastuzumab-containing arms over chemotherapy alone. Owing to these results, adjuvant regimens with trastuzumab and chemotherapy are now the standard of care for patients with HER2-positive operable breast cancer. However, because of different designs, these trials leave several questions open, which have practical as well as scientific implications. A debate exists around sequential or concomitant administration of trastuzumab with chemotherapy, treatment duration, minimization of cardiac risks and role of anthracyclines in trastuzumab-based regimens. This article will analyze the currently available data on trastuzumab in the adjuvant setting and discuss critical issues regarding its use.