Improved Prognosis by Trastuzumab of Women With <i>HER2</i>-Positive Breast Cancer Compared With Those With <i>HER2</i>-Negative Disease
Authors: Gianluigi Ferretti, Alessandra Fabi, Alessandra Felici, Paola Papaldo
Journal: Journal of Clinical Oncology (2010)

TO THE EDITOR: We have read with great interest the article by Dawood et al, and we think that the findings reported by the authors deserve some comments. Between June 2000 and January 2004, we consecutively enrolled 68 women with metastatic breast cancer: 33 patients received vinorelbine alone, while 35 patients were given trastuzumab plus vinorelbine according to human epidermal growth factor receptor-2 (HER2) expression determined by immunohistochemistry. This was formally a phase II study, which demonstrated that women with HER2-overexpressing metastatic breast cancer when treated with trastuzumab and vinorelbine had a better prognosis than those with HER2-negative disease treated with vinorelbine alone. In our study, the vast majority of patients received chemotherapy for metastatic disease. No one had previously received vinorelbine and only three women with HER2-positive disease had previously received trastuzumab for metastatic disease. Thus, by our findings, we provocatively suggested that the assumption that HER2positive tumors have a worse prognosis could be no longer valid when treated with trastuzumab. In fact, with the use of trastuzumab, women with HER2-positive disease appeared to do far better than did patients with HER2-negative tumors, exhibiting consistently higher rates of response, longer time to progression, and improved overall survival. Given that HER2-positive breast cancer is being treated as a distinct clinical entity, we cannot include women with HER2-positive breast cancer in trials recruiting patients regardless of HER2 status. Our study was criticized because it lacked a randomization plan. But, because in HER2-positive tumors chemotherapy alone as first-line treatment has been replaced with a combination of chemotherapy and trastuzumab, a trial without trastuzumab in HER2-positive patients with breast cancer would be ethically inappropriate. Thus, a prospective comparison between patients treated for HER2-positive disease and women treated for HER2-negative breast cancer can be formally performed only as a phase II study, in which consecutively enrolled patients with metastatic breast cancer are treated with chemotherapy with or without trastuzumab, according to HER2 status. Decades of randomized clinical trials on the first-line treatment of metastatic breast cancer have never been able to show so remarkable differences in time to progression and overall survival as the three fundamental randomized trials comparing chemotherapy with chemotherapy plus trastuzumab in women with HER2overexpressing metastatic breast cancer have been able to do. The merit of the study by Dawood et al is to have retrospectively compared the prognosis of three groups of patients: women with metastatic HER2-positive breast cancer with and without the addition of trastuzumab with women with HER2-negative disease. We agree with the authors that trastuzumab has not only beneficially changed the natural history of HER2-positive breast cancer, but it has also improved the prognostic outcomes of women with HER2overexpressing tumors beyond those of women with HER2negative disease.