Use of chemotherapy plus a monoclonal antibody against HER2 for metastaticbreast cancer that overexpresses HER2.

Background: The HER2 gene, which encodes the growth factor receptor HER2, i s amplified and HER2 is overexpressed in 25 to 30 percent of breast cancers , increasing the aggressiveness of the tumor. Methods: We evaluated the efficacy and safety of trastuzumab, a recombinant monoclonal antibody against HER2, in women with metastatic breast cancer t hat overexpressed HER2. We randomly assigned 234 patients to receive standa rd chemotherapy alone and 235 patients to receive standard chemotherapy plu s trastuzumab. Patients who had not previously received adjuvant (postopera tive) therapy with an anthracycline were treated with doxorubicin (or epiru bicin in the case of 36 women) and cyclophosphamide with (143 women) or wit hout trastuzumab (138 women). Patients who had previously received adjuvant anthracycline were treated with paclitaxel alone (96 women) or paclitaxel with trastuzumab (92 women). Results: The addition of trastuzumab to chemotherapy was associated with a longer time to disease progression (median, 7.4 vs. 4.6 months; P<0.001), a higher rate of objective response (50 percent vs. 32 percent, P<0.001), a longer duration of response (median, 9.1 vs. 6.1 months; P<0.001), a lower rate of death at 1 year (22 percent vs. 33 percent, P=0.008), longer surviv al (median survival, 25.1 vs. 20.3 months; P=0.046), and a 20 percent reduc tion in the risk of death. The most important adverse event was cardiac dys function, which occurred in 27 percent of the group given an anthracycline, cyclophosphamide, and trastuzumab; 8 percent of the group given an anthrac ycline and cyclophosphamide alone; 13 percent of the group given paclitaxel and trastuzumab; and 1 percent of the group given paclitaxel alone. Althou gh the cardiotoxicity was potentially severe and, in some cases, life-threa tening, the symptoms generally improved with standard medical management. Conclusions: Trastuzumab increases the clinical benefit of first-line chemo therapy in metastatic breast cancer that overexpresses HER2. (N Engl J Med 2001;344:783-92.) Copyright (C) 2001 Massachusetts Medical Society.