Quality-of-life-adjusted evaluation of adjuvant therapies for operable breast cancer. The International Breast Cancer Study Group OBJECTIVE: To evaluate a single cycle of adjuvant chemotherapy compared with longer duration chemotherapy for premenopausal women or chemoendocrine therapy for postmenopausal women with operable breast cancer using a quality-of-life-oriented end point, Q-TWiST (quality-adjusted analysis of TWiST: Time Without Symptoms and Toxicity). DESIGN: Multicenter randomized clinical trial--International Breast Cancer Study Group (IBCSG: formerly Ludwig Group) Trial V. SETTING: IBCSG participating centers in Sweden, Switzerland, Australia, Yugoslavia, Spain, New Zealand, Italy, Germany, and South Africa. PATIENTS: Data were available for 1229 eligible patients with node-positive breast cancer who were randomized to receive one of three adjuvant treatments after at least a total mastectomy and axillary clearance. INTERVENTIONS: Patients received either a single cycle of perioperative chemotherapy consisting of cyclophosphamide, methotrexate, fluorouracil, and leucovorin; or six cycles (6 months) of a conventionally timed chemotherapy consisting of cyclophosphamide, methotrexate, fluorouracil, and prednisone for premenopausal women or this combination plus tamoxifen for postmenopausal women; or both perioperative and conventionally timed chemotherapy for a 7-month course of adjuvant therapy. RESULTS: At 5 years of median follow-up, patients who received the longer duration therapies had an improved 5-year disease-free survival percentage (53% compared with 36%; P less than 0.001) and 5-year overall survival percentage (73% compared with 63%; P = 0.001) compared with those who received the single perioperative cycle alone. By 3.5 years, the greater burden of toxic effects associated with the longer duration treatments was balanced by their superior control of disease. Within 5 years of follow-up, even after subtracting time with adjuvant treatment toxicity, patients gained an average of 2.2 months of Q-TWiST if treated with the longer duration therapies compared with the single cycle (P = 0.03). The gain for premenopausal patients was 2.8 months (P = 0.05), whereas the gain for postmenopausal women was 1.5 months (P greater than 0.2). CONCLUSIONS: Six or seven months of adjuvant chemotherapy or chemoendocrine therapy improve both the quantity and quality of life for patients with node-positive breast cancer compared with a single short course of perioperative combination chemotherapy. 