Adjuvant therapy for HER2 positive breast cancer: are anthracyclines still necessary?

Anthracyclines are integral components of most adjuvant chemotherapy regimens for surgically removed early breast cancer and are central to the accepted treatment standards. Recently the standard anthracycline regimen of doxorubicin plus cyclophosphamide was found to be inferior in preventing recurrence of breast cancer when compared to cyclophosphamide and docetaxel, questioning the necessity to expose patients to the potential cardiotoxicity of anthracycline in the adjuvant setting. Trastuzumab, a humanized monoclonal antibody against the extracellular domain of the human epidermal growth factor receptor 2 (HER2) has become the cornerstone of treatment of breast cancers that overexpress HER2 in the neo-adjuvant and metastatic setting. Unfortunately, the combination of anthracyclines and trastuzumab produces a high incidence of cardiotoxicity as seen in early trials of metastatic breast cancer. Five adjuvant trials combining trastuzumab with different anthracycline-based regimens have been reported, all of them revealing similar efficacy in reducing recurrence of breast cancer. The trastuzumab adjuvant trial 006 from the Breast Cancer International Research Group shows for the first time that a nonanthracycline-containing regimen with trastuzumab has equivalent efficacy in decreasing the recurrence of breast cancer, with less incidence of cardiotoxicity when compared to anthracycline-containing trastuzumab adjuvant regimens. Further trials are needed to determine the optimal length of adjuvant therapy with trastuzumab, as well as long-term side effects with special attention to cardiotoxicity.