title: 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.
abstract: OBJECTIVE
  To investigate whether a short intensive course of perioperative polychemotherapy can change the course of early breast cancer.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University Hospital Leiden, Department of Surgery, the Netherlands.
authors.forename: P C
authors.initials: PC
authors.lastname: Clahsen
authors.forename: C J
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: J P
authors.initials: JP
authors.lastname: Julien
authors.forename: J L
authors.initials: JL
authors.lastname: Floiras
authors.forename: T
authors.initials: T
authors.lastname: Delozier
authors.forename: F Y
authors.initials: FY
authors.lastname: Mignolet
authors.forename: T M
authors.initials: TM
authors.lastname: Sahmoud
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005060:Europe; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008207:Lymphatic Metastasis; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D017698:Postmenopause; D017697:Premenopause
chemical_list: D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate