Randomized trial of low-dose chemotherapy added to tamoxifen in patients with receptor-positive and lymph node-positive breast cancer

Purpose: To evaluate the outcome in patients with stage It hormone receptor -positive breast cancer treated or not treated with low-dose, short-term ch emotherapy in addition to tamoxifen in terms of disease-free and overall su rvival. Patients and Methods: A total of 613 patients were randomized to receive ei ther low-dose chemotherapy (doxorubicin 20 mg/m(2) and vincristine 1 mg/m(2 ) on day 1; cyclophosphamide 300 mg/m(2); methotrexate 25 mg/m2; and fluoro uracil 600 mg/m(2) on days 29 and 36 intravenously) or no chemotherapy in a ddition to 20 mg of tamoxifen orally for 2 years. A third group without any treatment (postmenopausal patients only) was terminated after the accrual of 79 patients due to ethical reasons. Results: After a median follow-up period of 7.5 years, the addition of chem otherapy did not improve the outcome in patients as compared with those tre ated with tamoxifen alone, neither with respect to disease-free nor overall survival. Multivariate analysis of prognostic factors for disease-free sur vival revealed menopausal status, in addition to nodal status, progesterone receptor, and histologic grade as significant. Both untreated postmenopaus al and tamoxifen-treated premenopausal patients showed identical prognoses significantly inferior to the tamoxifen-treated postmenopausal cohort. Prog nostic factors for overall survival in the multivariate analysis showed nod al and tumor stage, tumor grade, and hormone receptor level as significant. Conclusion: Low-dose chemotherapy in addition ta tamoxifen does not improve the prognosis of stage II breast cancer patients with hormone-responsive t umors. Tamoxifen-treated postmenopausal patients show a significantly bette r prognosis than premenopausal patients, favoring the hypothesis of a more pronounced effect of tamoxifen in the older age groups. (C) 1999 by America n Society of Clinical Oncology.