Response to cyclophosphamide, methotrexate, and fluorouracil in lymph node-positive breast cancer according to HER2 overexpression and other tumor biologic variables

Purpose: There is considerable interest in biologic markers able to predict the response of cancer patients to therapy. HERS overexpression is a poten tial indicator of responsiveness to doxorubicin and paclitaxel and of unres ponsiveness to tamoxifen in breast carcinoma patients. However, the signifi cance of HERS overexpression in responsiveness to cyclophosphamide, methotr exate, and fluorouracil (CMF) has remained unclear. In this study, we inves tigated this issue in the 386 breast cancer patients in the first CMF contr olled clinical trial with a 20-year follow-up. Patients and Methods: Node-positive breast carcinoma patients were randomly assigned to receive either no further treatment after radical mastectomy(1 79 women) or 12 monthly cycles of adjuvant CMF chemotherapy (207 women). Ov erexpression of HERS and the status of other tumor variables was assessed b y immunohistochemistry in at least 324 (84%) of the 386 patients. Statistic al analyses were performed to assess the efficacy of CMF treatment for the subgroups defined by HERS and the status of other variables using a Bayesia n approach. The end points considered were relapse-free survival (RFS) and cause-specific survival (CSS), Results: Bayesian analysis of the treatment effect for HERS and other varia bles indicated a clinical benefit from CMF treatment in all subgroups defin ed according to variables status. In particular regarding HER2 status, Baye sian estimates of RFS hazard ratios were equal to 0.484 and 0.641 and estim ates of CSS hazard ratios were equal to 0.495 and 0.730 for HERS-positive a nd -negative tumors, respectively. Conclusion: CMF treatment showed a clinical benefit in the considered subgr oups, defined according to HERS and other tumor variables status, Patients with HER2-positive or HER2-negative tumors benefit from CMF treatment, and the poor prognosis associated with the HERS overexpression in the untreated group could be completely overcome by the chemotherapy treatment. J Clin O ncol 19:329-335, (C) 2001 by American Society of Clinical Oncology.