Postchemotherapy adjuvant tamoxifen therapy beyond five years in patients with lymph node-positive breast cancer. Eastern Cooperative Oncology Group.

BACKGROUND: Data from a pilot study published in 1984 suggested that tamoxifen administration (as adjuvant hormonal therapy) for more than 5 years after initial breast cancer surgery might have therapeutic benefit.

PURPOSE: A randomized trial was performed to assess the efficacy of maintaining tamoxifen therapy beyond 5 years in women with axillary lymph node-positive breast cancer who had been treated with surgery followed by 1 year of chemotherapy and 5 years of tamoxifen.

METHODS: One hundred ninety-four women (87 postmenopausal and 107 premenopasual) enrolled in two concurrent Eastern Cooperative Oncology Group adjuvant trials (E4181 for postmenopausal patients and E5181 for premenopausal patients) were randomly assigned to continued tamoxifen therapy or observation. Data for 193 women (87 postmenopausal and 106 premenopausal) were available for analysis. Median follow-up is 5.6 years since the randomization at 5 years, with the longest follow-up being 8.0 years. The major analyses measured events from the time of randomization until relapse or death; these included time-to-relapse analyses, with new opposite-breast cancers counted as treatment failures, and survival analyses. Time-to-relapse comparisons and survival comparisons for women in the two treatment groups were made by use of the Kaplan-Meier method and the logrank test. Reported P values are two-sided.

RESULTS: Five years after the randomization, no statistically significant differences were noted in either time to relapse or survival between women continuing to receive tamoxifen and those on observation. Eight-five percent of the women receiving tamoxifen were disease free at this time compared with 73% of those on observation (P = .10); survival was 86% for those continuing to receive tamoxifen and 89% for those on observation (P = .52). Differences in the time to relapse and survival between premenopausal and postmenopausal women assigned to the two treatment groups were also not statistically significant (time to relapse: P = .38 and P = .16 for premenopausal and postmenopausal patients, respectively; survival; P = .18 and P = .72 for premenopausal and postmenopausal patients, respectively). There was an indication that women with estrogen receptor-positive tumors may experience a longer time to relapse with continued tamoxifen therapy (P = .014); however, the survival difference for this subgroup was not statistically significant (P = .81). The toxicity patterns in the two treatment groups were similar.

CONCLUSIONS AND IMPLICATIONS: Our results suggest that further evaluation of adjuvant tamoxifen therapy beyond 5 years in women with axillary lymph node-positive, estrogen receptor-positive breast cancer who have also been treated with adjuvant chemotherapy would be appropriate.