Tamoxifen adjuvant treatment duration in early breast cancer: Initial results of a randomized study comparing short-term treatment with long-term treatment

purpose: In 1986, The Federation Nationale des Centres de Lune Contre le Ca ncer Breast Group initiated a multicenter randomized trial to assess the us efulness of long-term adjuvant tamoxifen treatment. Short-term adjuvant tam oxifen treatment wets to be compared with lifelong adjuvant tamoxifen treat ment. Patients and Methods: Patients who were disease-free after 2 to 3 years of adjuvant tamoxifen treatment were eligible for the trial. From September 19 85 to May 1995, 3,793 patients were randomized from France, Belgium, and Ar gentina. A total of 1,882 patients stopped tamoxifen (short-term group), an d 1,911 patients were to continue tamoxifen for life (long-term group) at t he same dose as previously prescribed. The protocol was modified in Februar y 1997, limiting tamoxifen treatment to 10 years after randomization, thus giving a comparison between a 2- to 3-year treatment and a 12- to 13-year t reatment. To date, the median duration of tamoxifen treatment is 30 months in the short-term group, and 70 months in the long-term group. Results: Overall, longer tamoxifen treatment induced a 23% reduction in rel apse rates, leading to a 7-year disease-free survival rate of 78%, compared with 72% in the shorter-treatment group. In contrast, overall survival did not differ between the two groups, with a 79% overall survival rate in bot h groups. This improvement in disease-free survival could be observed in no de-positive patients (P = .001); however, it was not found in node-negative patients. Prolonged tamoxifen treatment corresponded to a significant incr ease in disease-free survival in estrogen receptor-positive patients (P = . 03) as well as in estrogen receptor-negative patients (P = .05). Furthermor e, longer treatment reduced contralateral breast cancers and did not increa se the number of endometrial cancers. Conclusion: Although no survival advantage was noted, patients did benefit from longer tamoxifen treatment over 3 years and had significantly better d isease-free survival compared with patients who stopped hormonal treatment. Long-term follow-up is needed to assess these results. Most patients in th e long-term group are still receiving treatment. Comparison of results as t ime passes will enable conclusions to be made on the value of long-term tre atment over 5 years compared with 2 to 3 years. (C) 2000 by American Societ y of Clinical Oncology.