| Title | Endocrine responsiveness and tailoring adjuvant therapy for postmenopausal lymph node-negative breast cancer: a randomized trial. | | Author(s) | International Breast Cancer Study Group | | Source | J Natl Cancer Inst 2002 Jul 17; 94(14):1054-65. | | MeSH | Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Hormonal
Antineoplastic Combined Chemotherapy Protocols
Breast Neoplasms
Chemotherapy, Adjuvant
Cyclophosphamide
Endocrine System
Fluorouracil
Humans
Lymphatic Metastasis
Methotrexate
Middle Aged
Postmenopause
Quality of Life
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Tamoxifen
Time Factors
Treatment Outcome
| | 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 1 and 8, intravenously; and 5-fluorouracil at 600 mg/m(2) on days 1 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. | | Language | eng | | Pub Type(s) | Clinical Trial
Journal Article
Randomized Controlled Trial
| | PubMed ID | 12122096 |
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