Improved local control and disease-free survival after perioperative chemotherapy for early-stage breast cancer. A European Organization for Research and Treatment of Cancer Breast Cancer Cooperative Group Study

J Clin Oncol. 1996 Mar;14(3):745-53. doi: 10.1200/JCO.1996.14.3.745.

Abstract

Purpose: To investigate whether a short intensive course of perioperative polychemotherapy can change the course of early breast cancer.

Patients and methods: A total of 2,795 women with early breast cancer, stage I to IIIA, were randomized onto a trial (European Organization for Research and Treatment of Cancer [EORTC] 10854) to compare surgery followed by one course of perioperative chemotherapy versus surgery alone. Patients assigned to the chemotherapy arm received one course of fluorouracil 600 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 600 mg/m2 (FAC) intravenously, within 24 hours after surgery. In both randomized treatment arms, a recommendation was made for premenopausal women with positive axillary nodes to receive prolonged courses of cyclophosphamide, methotrexate, and fluorouracil (CMF), according to the standard treatment for this subgroup.

Results: At a median follow-up time of 41 months, local control was significantly better in the perioperative treatment arm as compared with the observation arm (hazards ratio, 0.60; 95% confidence interval, 0.44 to 0.83; P < .01). Disease-free survival was significantly prolonged in the chemotherapy arm (hazards ratio, 0.84; 95% confidence interval, 0.70 to 0.99; P = .04). Premenopausal node-negative patients especially showed an advantage for the perioperative chemotherapy arm. No advantage for perioperative chemotherapy was observed in premenopausal node-positive women who also had received prolonged chemotherapy.

Conclusion: We conclude that one course of perioperative FAC is able to improve local control and can prolong disease-free survival in women with early breast cancer. However, our results also suggest that a perioperative timing cannot improve the results of standard prolonged chemotherapy in premenopausal women with positive axillary nodes.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery*
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Europa
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Lymphatic Metastasis
  • Methotrexate / administration & dosage
  • Middle Aged
  • Postmenopause
  • Premenopause

Substances

  • Doxorubicin
  • Cyclophosphamide
  • Cisplatin
  • Fluorouracil
  • Methotrexate

Supplementary concepts

  • CAF protocol
  • CMF protocol