Adjuvant trastuzumab for breast cancer. A second look. Longer follow-up confirms improved overall survival.

Adjuvant cytotoxic chemotherapy following surgical treatment of nonmetastatic breast cancer usually includes an anthracycline. The addition of trastuzumab should be considered for women whose tumours overexpress HER-2 protein. Trastuzumab has been approved in the European Union since 2006 for adjuvant treatment of breast cancer. In 2011, the indications were further specified to allow the use of adjuvant trastuzumab in both anthracycline-based and non-anthracycline protocols. In 2006, the results of the first 3 trials of adjuvant chemotherapy showed an absolute gain in overall survival of about 4% after 4 years with trastuzumab. Updates of these trials, with longer follow-up, along with the results of a fourth trial, confirm the overall survival benefit, whether or not the adjuvant regimen includes an anthracycline (about 91% versus 87%). Trastuzumab carries a risk of NYHA class III or IV congestive heart failure with reduced left ventricular ejection fraction. The risk is higher in patients who receive the doxorubicin + cyclophosphamide combination, one-third of whom have a reduction in left ventricular ejection fraction that persists for several years after the end of treatment. The nature of non-cardiac serious adverse effects depends on whether the protocol includes an anthracycline: anthracycline therapy is associated with more frequent arthralgia, myalgia, hand-foot syndrome, vomiting, leukopenia and neutropenia, while regimens not containing an anthracycline are associated with more anaemia and thrombocytopenia. In practice, in 2012, the addition of trastuzumab to cytotoxic chemotherapy remains a valid option for women who have undergone surgery for nonmetastatic invasive breast tumours that overexpress HER-2 protein. It remains to be shown whether anthracycline-free chemotherapy regimens, which are less cardiotoxic, are equally effective.