title: A randomized placebo-controlled study of tamoxifen after adjuvant chemotherapy in premenopausal women with early breast cancer (National Cancer Institute of Canada--Clinical Trials Group Trial, MA.12).
abstract: BACKGROUND
  In the early 1990s, the role of adjuvant tamoxifen in premenopausal women with early breast cancer (EBC) was not established. Similarly, optimum timing relative to adjuvant chemotherapy and efficacy of tamoxifen in hormone receptor-negative tumors were unclear.
  
  
  METHODS
  Premenopausal women with EBC, any hormone receptor status, after surgery received standard adjuvant chemotherapy [doxorubicin (adriamycin)/cyclophosphamide, cyclophosphamide/methotrexate/5-fluorouracil, or cyclophosphamide/epirubicin/5-fluorouracil] followed by randomization to tamoxifen or placebo for 5 years. Outcomes were overall survival (OS), disease-free survival (DFS), toxicity, and compliance with therapy.
  
  
  RESULTS
  Median follow-up for 672 women was 9.7 years. Multivariate analysis showed improved DFS [78.2% versus 71.3% at 5 years; hazard ratio (HR) 0.77; P = 0.056] and a trend for improved OS (86.6% versus 82.1% at 5 years; HR 0.78; P = 0.12). There was no evidence of greater benefit for the receptor-positive subgroup. Compliance with treatment was suboptimal in both arms, with 103 (31%) women on tamoxifen and 70 (21%) on placebo-stopping therapy early because of toxicity, refusal, or other choices.
  
  
  CONCLUSIONS
  Adjuvant tamoxifen, given after chemotherapy to premenopausal women with EBC, improved 5-year DFS. Poor compliance may have reduced treatment efficacy.
authors.affiliation: Department of Medical Oncology, Tom Baker Cancer Centre, Calgary, Alberta. Electronic address: vivienbr@cancerboard.ab.ca.
authors.forename: V H C
authors.initials: VHC
authors.lastname: Bramwell
authors.affiliation: Department of Medical Oncology, Sunnybrook Odette Cancer Centre, Toronto, Ontario.
authors.forename: K I
authors.initials: KI
authors.lastname: Pritchard
authors.affiliation: Central Office, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario.
authors.forename: D
authors.initials: D
authors.lastname: Tu
authors.affiliation: Department of Medical Oncology, Cross Cancer Institute, Edmonton, Alberta.
authors.forename: K
authors.initials: K
authors.lastname: Tonkin
authors.affiliation: Department of Radiation Oncology, Saskatoon Cancer Centre, Saskatoon, Saskatchewan.
authors.forename: H
authors.initials: H
authors.lastname: Vachhrajani
authors.affiliation: Department of Medical Oncology, London Regional Cancer Program, London, Ontario.
authors.forename: T A
authors.initials: TA
authors.lastname: Vandenberg
authors.affiliation: Department of Surgical Oncology, Hôpital Du Saint-Sacrement, Quebec City, Quebec.
authors.forename: J
authors.initials: J
authors.lastname: Robert
authors.affiliation: Department of Medical Oncology, Juravinski Cancer Centre, Hamilton, Ontario.
authors.forename: A
authors.initials: A
authors.lastname: Arnold
authors.affiliation: Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: S E
authors.initials: SE
authors.lastname: O'Reilly
authors.affiliation: Central Office, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario.
authors.forename: B
authors.initials: B
authors.lastname: Graham
authors.affiliation: Central Office, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario.
authors.forename: L
authors.initials: L
authors.lastname: Shepherd
mesh_terms: D000047:Academies and Institutes; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002170:Canada; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008197:Lymph Node Excision; D008408:Mastectomy / Q000379:methods; D008875:Middle Aged; D010919:Placebos; D017697:Premenopause / Q000187:drug effects; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D010919:Placebos; D013629:Tamoxifen