title: The effect of endocrine responsiveness on high-risk breast cancer treated with dose-intensive chemotherapy: results of International Breast Cancer Study Group Trial 15-95 after prolonged follow-up.
abstract: BACKGROUND
  The role of adjuvant dose-intensive chemotherapy and its efficacy according to baseline features has not yet been established.
  
  
  METHODS
  Three hundred and forty-four patients were randomized to receive seven courses of standard-dose chemotherapy (SD-CT) or three cycles of dose-intensive epirubicin and cyclophosphamide (epirubicin 200 mg/m(2) plus cyclophosphamide 4 mg/m(2) with filgrastim and progenitor cell support). All patients were assigned tamoxifen at the completion of chemotherapy. The primary end point was disease-free survival (DFS). This paper updates the results and explores patterns of recurrence according to predicting baseline features.
  
  
  RESULTS
  At 8.3-years median follow-up, patients assigned DI-EC had a significantly better DFS compared with those assigned SD-CT [8-year DFS percent 47% and 37%, respectively, hazard ratio (HR) 0.76; 95% confidence interval 0.58-1.00; P = 0.05]. Only patients with estrogen receptor (ER)-positive disease benefited from the DI-EC (HR 0.61; 95% confidence interval 0.39, 0.95; P = 0.03).
  
  
  CONCLUSIONS
  After prolonged follow-up, DI-EC significantly improved DFS, but the effect was observed only in patients with ER-positive disease, leading to the hypothesis that efficacy of DI-EC may relate to its endocrine effects. Further studies designed to confirm the importance of endocrine responsiveness in patients treated with dose-intensive chemotherapy are encouraged.
authors.affiliation: Department of Medicine, Research Unit in Medical Senology, European Institute of Oncology, Milan, Italy. marco.colleoni@ieo.it
authors.forename: M
authors.initials: M
authors.lastname: Colleoni
authors.forename: Z
authors.initials: Z
authors.lastname: Sun
authors.forename: G
authors.initials: G
authors.lastname: Martinelli
authors.forename: R L
authors.initials: RL
authors.lastname: Basser
authors.forename: A S
authors.initials: AS
authors.lastname: Coates
authors.forename: R D
authors.initials: RD
authors.lastname: Gelber
authors.forename: M D
authors.initials: MD
authors.lastname: Green
authors.forename: F
authors.initials: F
authors.lastname: Peccatori
authors.forename: S
authors.initials: S
authors.lastname: Cinieri
authors.forename: S
authors.initials: S
authors.lastname: Aebi
authors.forename: G
authors.initials: G
authors.lastname: Viale
authors.forename: K N
authors.initials: KN
authors.lastname: Price
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
mesh_terms: D000328:Adult; D000368:Aged; D000568:Amenorrhea; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011994:Recombinant Proteins; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013629:Tamoxifen / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D013629:Tamoxifen; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D003520:Cyclophosphamide; D000069585:Filgrastim