title: Differential efficacy of three cycles of CMF followed by tamoxifen in patients with ER-positive and ER-negative tumors: long-term follow up on IBCSG Trial IX.
abstract: BACKGROUND
  The benefit of adjuvant chemotherapy in postmenopausal patients with estrogen receptor (ER)-positive lymph node-negative breast cancer is being reassessed.
  
  
  METHODS
  After stratification by ER status, 1669 postmenopausal patients with operable lymph node-negative breast cancer were randomly assigned to three 28-day courses of 'classical' CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy followed by tamoxifen for 57 months (CMF→tamoxifen) or to tamoxifen alone for 5 years.
  
  
  RESULTS
  ERs were positive in 81% of tumors. At a median follow-up of 13.1 years, patients with ER-positive breast cancers did not benefit from CMF [13-year disease-free survival (DFS) 64% CMF→tamoxifen, 66% tamoxifen; P = 0.99], whereas CMF substantially improved the prognosis of patients with ER-negative breast cancer (13-year DFS 73% versus 57%, P = 0.001). Similarly, breast cancer-free interval (BCFI) was identical in the ER-positive cohort but significantly improved by chemotherapy in the ER-negative cohort (13-year BCFI 80% versus 63%, P = 0.001). CMF had no influence on second nonbreast malignancies or deaths from other causes.
  
  
  CONCLUSIONS
  CMF is not beneficial in postmenopausal patients with node-negative ER-positive breast cancer but is highly effective within the ER-negative cohort. In the future, other markers of chemotherapy response may define a subset of patients with ER-positive tumors who may benefit from adjuvant chemotherapy.
authors.affiliation: Division of Medical Oncology, Berne University Hospital and Swiss Group for Clinical Cancer research (SAKK), Berne, Switzerland. Electronic address: stefan.aebi@onkologie.ch.
authors.forename: S
authors.initials: S
authors.lastname: Aebi
authors.affiliation: IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston.
authors.forename: Z
authors.initials: Z
authors.lastname: Sun
authors.affiliation: IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston.
authors.forename: D
authors.initials: D
authors.lastname: Braun
authors.affiliation: IBCSG Statistical Center and Frontier Science and Technology Research Foundation, Boston, USA.
authors.forename: K N
authors.initials: KN
authors.lastname: Price
authors.affiliation: Medical Onco-Gynecology Unit, Department of Medicine, Geneva University Hospital, Geneva.
authors.forename: M
authors.initials: M
authors.lastname: Castiglione-Gertsch
authors.affiliation: IBCSG Coordinating Center and Inselspital, Berne, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Rabaglio
authors.affiliation: IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Frontier Science and Technology Research Foundation, Harvard School of Public Health, Harvard Medical School, Boston, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Gelber
authors.affiliation: Department of Medical Oncology, Centro di Riferimento Oncologico, Aviano, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Crivellari
authors.affiliation: Department of Surgical Oncology, Institute of Oncology, Ljulbljana, Slovenia.
authors.forename: J
authors.initials: J
authors.lastname: Lindtner
authors.affiliation: Department of Medical Oncology, St Vincent's Hospital, Melbourne, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Snyder
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Karlsson
authors.affiliation: Department of Medical Oncology, Spedali Civili di Brescia, Brescia, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Simoncini
authors.affiliation: IBCSG Pathology Review Office, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
authors.forename: B A
authors.initials: BA
authors.lastname: Gusterson
authors.affiliation: IBCSG Pathology Office, Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Viale
authors.affiliation: IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston.
authors.forename: M M
authors.initials: MM
authors.lastname: Regan
authors.affiliation: International Breast Cancer Study Group, Berne, Switzerland; School of Public Health, University of Sydney, Australia.
authors.forename: A S
authors.initials: AS
authors.lastname: Coates
authors.affiliation: Department of Medicine, European Institute of Oncology, Milan, Italy; Department of Medical Oncology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D013629:Tamoxifen / Q000008:administration & dosage
chemical_list: D011960:Receptors, Estrogen; D013629:Tamoxifen; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate