Adjuvant Chemotherapy Followed by Goserelin Versus Either Modality Alone for Premenopausal Lymph Node-Negative Breast Cancer: A Randomized Trial International Breast Cancer Study Group (IBCSG) 1

Background: Although chemotherapy and ovarian function suppression are both effective adjuvant therapies for patients with early-stage breast cancer, little is known of the effi cacy of their sequential combination. In an International Breast Cancer Study Group (IBCSG) randomized clinical trial (Trial VIII) for pre- and perimenopausal women with lymph node–negative breast cancer, we compared sequential chemotherapy followed by the gonadotropin-releasing hormone agonist goserelin with each modality alone. Methods: From March 1990 through October 1999, 1063 patients stratifi ed by estrogen receptor (ER) status and radiotherapy plan were randomly assigned to receive goserelin for 24 months (n 346), six courses of “classical” CMF (cyclophosphamide, methotrexate, 5-fl uorouracil) chemotherapy (n 360), or six courses of classical CMF followed by 18 months of goserelin (CMF3 goserelin; n 357). A fourth arm (no adjuvant treatment) with 46 patients was discontinued in 1992. Tumors were classifi ed as ER-negative (30%), ERpositive (68%), or ER status unknown (3%). Twenty percent of patients were aged 39 years or younger. The median follow-up was 7 years. The primary outcome was diseasefree survival (DFS). Results: Patients with ER-negative tumors achieved better disease-free survival if they received CMF (5-year DFS for CMF 84%, 95% confi dence interval [CI] 77% to 91%; 5-year DFS for CMF3 goserelin 88%, 95% CI 82% to 94%) than if they received goserelin alone (5-year DFS 73%, 95% CI 64% to 81%). By contrast, for patients with ER-positive disease, chemotherapy alone and goserelin alone provided similar outcomes (5-year DFS for both treatment groups 81%, 95% CI 76% to 87%), whereas sequential therapy (5-year DFS 86%, 95% CI 82% to 91%) provided a statistically nonsignifi cant improvement compared with either modality alone, primarily because of the results among younger women. Conclusions: Premenopausal women with ERnegative (i.e., endocrine nonresponsive), lymph node–negative breast cancer should receive adjuvant chemotherapy.