title: Significance of relapse after adjuvant treatment with combination chemotherapy or 5-fluorouracil alone in high-risk breast cancer. A Western Cancer Study Group Project.
abstract: Beginning in 1974, patients undergoing mastectomy at high risk for recurrence (greater than or equal to 4 nodes positive; median, 9.4 positive; range, 4 to 28) were randomized after stratification for menopausal status and radiotherapy to receive either 5-fluorouracil (5-FU, 500 mg/sq m i.v. every week) or cyclophosphamide, 400 mg/sq m; methotrexate, 30 mg/sq m; and 5-FU, 500 mg/sq m (CMF; all given i.v. every 2 weeks) in a 12-month program. All 62 patients remain evaluable with median follow-up now exceeding 70 months (range, 60 to 80 months). CMF significantly prevented early disease recurrence (97% relapse free on CMF versus 75% on 5-FU at 12 months; p less than 0.05) and demonstrated survival advantage during the initial 40-month follow-up. This significance was subsequently lost, and the percentages of relapse free and overall survival after 70 months are: (formula, see text) The apparently paradoxical relationship between relapse and survival on the 5-FU arm was related to survival after recurrence. Survival after recurrence was significantly longer on the 5-FU compared to the CMF arm (median of greater than 38 versus 10 months, respectively; p less than 0.01). These results suggest (a) long-term survival in adjuvant trials cannot be accurately predicted by short-term differences in relapse frequency, (b) survival after relapse may be influenced by the antecedent adjuvant therapy received, and (c) disease relapse does not necessarily preclude long-term survival.
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D003520:Cyclophosphamide / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008408:Mastectomy; D008593:Menopause; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D011897:Random Allocation
chemical_list: D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate