Endocrine Responsiveness and Tailoring Adjuvant Therapy for Postmenopausal Lymph Node-Negative Breast Cancer: A Randomized Trial

International Breast Cancer Study Group (IBCSG), (2002) Endocrine Responsiveness and Tailoring Adjuvant Therapy for Postmenopausal Lymph Node-Negative Breast Cancer: A Randomized Trial. Journal of the National Cancer Institute, 94(14), pp. 1054-1065. (doi: 10.1093/jnci/94.14.1054)

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Publisher's URL: http://dx.doi.org/10.1093/jnci/94.14.1054

Abstract

Background: The role of adjuvant chemotherapy in postmenopausal patients with lymph node-negative breast cancer is controversial. After demonstrating the efficacy of chemotherapy combined with tamoxifen for postmenopausal patients with lymph node-positive disease, the International Breast Cancer Study Group launched a randomized trial (Trial IX) to evaluate the role of adjuvant chemotherapy preceding treatment with tamoxifen for patients with lymph node-negative disease. Methods: After stratification by estrogen receptor (ER) status, patients were randomly assigned to receive three 28-day courses of "classical" adjuvant CMF chemotherapy (cyclophosphamide at 100 mg/m(2) on days 1-14, orally; methotrexate at 40 mg/m(2) on days I and 8, intravenously; and 5-fluorouracil at 600 mg/m(2) on days I and 8, intravenously) followed by tamoxifen (20 mg/day, orally for 57 months) (CMF-->tamoxifen) or to receive tamoxifen alone (20 mg/day, orally for 60 months). We enrolled 1669 eligible patients, 382 (23%) with ER-negative tumors, 1217 (73%) with ER-positive tumors, and 70 (4%) with unknown ER status. The median follow-up was 71 months. All statistical tests were two-sided. Results: The added benefit of CMF followed by tamoxifen over tamoxifen alone was statistically significantly dependent on ER status (tests for interaction: P =.01 for disease-free survival [DFS] and P =.07 for overall survival [OS]), For patients with ER-negative tumors, the addition of CMF statistically significantly improved DFS (5-year DFS = 84% for CMF-->tamoxifen versus 69% for tamoxifen alone; difference = 15%; 95% confidence interval [CI] = 6% to 24%; risk ratio [RR] = 0.52; 95% CI = 0.34 to 0.79; P =.003) and OS (5-year OS = 89% for CMF-->tamoxifen versus 81% for tamoxifen alone; difference = 8%; 95% CI = 0% to 16%; RR = 0.51; 95% CI = 0.30 to 0.87; P =.01). By contrast, for patients with ER-positive tumors, addition of CMF provided no benefit in terms of DFS (5-year DFS = 84% for CMF-->tamoxifen versus 85% for tamoxifen alone; difference = -1; 95% CI = -6% to 4%; RR = 0.99, 95% CI = 0.75 to 1.30; P = .92) or OS (5-year OS = 95% for CMF-->tamoxifen versus 93%, for tamoxifen alone; difference = 2%; 95% CI=-1% to 5%, RR=0.95; 95% CI=0.64 to 1.40; P = .80). Conclusions: Postmenopausal patients with lymph node-negative breast cancer benefited substantially from adjuvant chemotherapy if their cancer was ER-negative (i.e., endocrine-nonresponsive). In contrast, if their cancer was ER-positive (i.e., endocrine-responsive), they obtained no benefit from the combination treatment compared with tamoxifen alone.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gusterson, Professor Barry
Authors: International Breast Cancer Study Group (IBCSG),
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Journal of the National Cancer Institute
ISSN:0027-8874

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