Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide for operable HER2-positive breast cancer.

Correspondence: Gianluigi Ferretti, M.D., Ph.D., Department of Medical Oncology, Regina Elena Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy. Telephone: 011390652665354; Fax: 011390652665637; e-mail: [email protected] Received February 1, 2006; accepted for publication March 16, 2006. ©AlphaMed Press 1083-7159/2006/$20.00/0 Concerning the controversies in the use of trastuzumab for early-stage breast cancer, Cianfrocca and Gradishar [1] have recently reported that an unplanned interim analysis of the North Central Cancer Treatment Group N9831 trial revealed a 36% relative reduction in the risk for recurrence for concurrent compared with sequential trastuzumab (p = .0114) [2], even though further follow-up is needed to ascertain whether this trend continues. Romond et al. [3] have recently presented the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer. The authors conclude that trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer. In trial B-31, 805 patients received doxorubicin and cyclophosphamide every 21 days for four cycles followed by paclitaxel every 3 weeks for four cycles plus weekly trastuzumab for 52 weeks; in only 59 patients, paclitaxel was given weekly for 12 weeks. In trial N9831, 808 patients were administered doxorubicin and cyclophosphamide as in trial B-31 but followed by 12 weekly doses of paclitaxel plus weekly trastuzumab for 52 weeks. It might be highlighted that exposure to lower and more frequent doses of paclitaxel could potentially exploit antiangiogenic and proapoptotic effects [4]. In metastatic breast cancer, weekly administration of paclitaxel has been reported to be superior to once-every-3-weeks administration [5]. As primary systemic chemotherapy, weekly paclitaxel, compared with once-every-3-weeks administration, improved the likelihood of pathologic complete remission [6]. By contrast, Romond et al. [3] assert that there was no evidence that the benefit of trastuzumab differed significantly between the B-31 and N9831 trials. The finding that the same effect of trastuzumab was observed in both the studies deserves further investigation, given the difference in the paclitaxel schedule.