Should trastuzumab be administered concomitantly with anthracycline in women with early, HER2-positive breast cancer?

Clinical targeting of the human epidermal growth factor receptor 2 (HER2) has dramatically improved the outlook of a subset of about 15% of breast cancers carrying HER2 gene amplification and/ or HER2 protein overexpression. Since the initial experiences with the anti-HER2 monoclonal antibody trastuzumab, it was clear that combination with conventional chemotherapy was required to exploit the full potential of HER2-targeting. However, prohibitive rates of cardiac toxicity were observed when trastuzumab was given concurrently with anthracyclines, which are compounds that have played a pivotal role in the treatment of breast cancer for decades. While most of the anti-HER2 programs have been designed as to avoid concomitance with anthracyclines, high rates of pathological complete remission were obtained in carefully selected patients with operable breasts cancer receiving concomitant trastuzumab and anthracycline in the preoperative setting. A recently published randomized study compared directly the current standard of sequential anthracycline followed by concomitant taxane and trastuzumab with a reversed sequence of taxanes followed by anthracyclines with trastuzumab administered concurrently with the whole program as neoadjuvant treatment for patients with early, operable breast cancer. The practical question asked by this study was whether a potential increase in the efficacy of trastuzumab based regimens could be worth the risk of giving it in concomitance with anthracyclines. This editorial will review the background of this study and discuss the impact of its results on the current clinical practice and on future research in the field.