title: Long-term results of International Breast Cancer Study Group Trial VIII: adjuvant chemotherapy plus goserelin compared with either therapy alone for premenopausal patients with node-negative breast cancer.
abstract: BACKGROUND
  The International Breast Cancer Study Group Trial VIII compared long-term efficacy of endocrine therapy (goserelin), chemotherapy [cyclophosphamide, methotrexate and fluorouracil (CMF)], and chemoendocrine therapy (CMF followed by goserelin) for pre/perimenopausal women with lymph-node-negative breast cancer.
  
  
  METHODS
  From 1990 to 1999, 1063 patients were randomized to receive (i) goserelin for 24 months (n = 346), (ii) six courses of 'classical' CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy (n = 360), or (iii) six courses of CMF plus 18 months goserelin (CMF→ goserelin; n = 357). Tumors were classified as estrogen receptor (ER) negative (19%), ER positive (80%), or ER unknown (1%); 19% of patients were younger than 40. Median follow-up was 12.1 years.
  
  
  RESULTS
  For the ER-positive cohort, sequential therapy provided a statistically significant benefit in disease-free survival (DFS) (12-year DFS = 77%) compared with CMF alone (69%) and goserelin alone (68%) (P = 0.04 for each comparison), due largely to the effect in younger patients. Patients with ER-negative tumors whose treatment included CMF had similar DFS (12-year DFS CMF = 67%; 12-year DFS CMF→ goserelin = 69%) compared with goserelin alone (12-year DFS = 61%, P= NS).
  
  
  CONCLUSIONS
  For pre/perimenopausal women with lymph-node-negative ER-positive breast cancer, CMF followed by goserelin improved DFS in comparison with either modality alone. The improvement was the most pronounced in those aged below 40, suggesting an endocrine effect of prolonged CMF-induced amenorrhea.
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. per.karlsson@oncology.gu.se
authors.forename: P
authors.initials: P
authors.lastname: Karlsson
authors.forename: Z
authors.initials: Z
authors.lastname: Sun
authors.forename: D
authors.initials: D
authors.lastname: Braun
authors.forename: K N
authors.initials: KN
authors.lastname: Price
authors.forename: M
authors.initials: M
authors.lastname: Castiglione-Gertsch
authors.forename: M
authors.initials: M
authors.lastname: Rabaglio
authors.forename: R D
authors.initials: RD
authors.lastname: Gelber
authors.forename: D
authors.initials: D
authors.lastname: Crivellari
authors.forename: J
authors.initials: J
authors.lastname: Collins
authors.forename: E
authors.initials: E
authors.lastname: Murray
authors.forename: K
authors.initials: K
authors.lastname: Zaman
authors.forename: M
authors.initials: M
authors.lastname: Colleoni
authors.forename: B A
authors.initials: BA
authors.lastname: Gusterson
authors.forename: G
authors.initials: G
authors.lastname: Viale
authors.forename: M M
authors.initials: MM
authors.lastname: Regan
authors.forename: A S
authors.initials: AS
authors.lastname: Coates
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D017273:Goserelin / Q000008:administration & dosage; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D017697:Premenopause; D011960:Receptors, Estrogen / Q000096:biosynthesis
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D017273:Goserelin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate