title: Estrogen receptor, Progesterone receptor, HER2 status and Ki67 index and responsiveness to adjuvant tamoxifen in postmenopausal high-risk breast cancer patients enrolled in the DBCG 77C trial.
abstract: BACKGROUND
  The DBCG 77C trial compared one year of tamoxifen in postmenopausal, steroid-receptor unknown, high-risk breast cancer patients to no adjuvant systemic therapy. After a potential follow-up of 30years we report overall efficacy of the study and results according to subtypes subsequently assessed by immunohistochemistry and fluorescent in situ hybridisation (FISH).
  
  
  METHODS
  Between 1977 and 1982, 1716 postmenopausal patients with tumours larger than 5cm or positive axillary nodes were randomly assigned to no systemic therapy or tamoxifen 30mg daily for one year. Archival tumour tissue from 1515 patients was analysed and the hormone receptor positive (estrogen receptor (ER) and/or progesterone receptor (PR)) cancers were defined as luminal A if Ki67 low and HER2-negative; as luminal B if Ki67 high or HER2-positive; and otherwise as non-luminal-HER2 positive or triple negative.
  
  
  RESULTS
  In the intent-to-treat (ITT) population one year of tamoxifen improved the disease-free-survival (DFS) (hazard ratio (HR)=0.87; 95% confidence interval (CI) 0.77-0.98), the Breast Cancer Recurrence Rate (BCRR) (HR=0.79; 0.69-0.90) and reduced the breast-cancer-specific-mortality (BCM) (HR=0.83; 0.73-0.93). BCRR were improved significantly by tamoxifen in luminal A (HR=0.66; 0.53-0.84) and luminal B/HER2- (HR=0.54; 0.39-0.74) but not in the other subsets, and with similar results for BCM with 30years follow-up.
  
  
  CONCLUSIONS
  One year of treatment with tamoxifen significantly improves BCRR and BCM in postmenopausal patients with ER positive breast cancers. The relative benefit from tamoxifen was not significantly different in luminal A and B subtypes.
  
  
  BACKGROUND
  The Danish Breast Cancer Cooperative Group (DBCG) prepared the original protocol (DBCG 77C) and was the sponsor of the study. Funding was not provided to the participating departments. The biomarker study was supported by grants from the Clinical Institute, Odense University.
authors.affiliation: Department of Oncology, Odense University Hospital, Odense, Denmark; Department of Oncology, Rigshospitalet, Copenhagen, Denmark. Electronic address: knoop@dadlnet.dk.
authors.forename: Ann S
authors.initials: AS
authors.lastname: Knoop
authors.affiliation: Department of Pathology, Slagelse Hospital, Slagelse, Denmark.
authors.forename: Anne-Vibeke
authors.initials: AV
authors.lastname: Lænkholm
authors.affiliation: Danish Breast Cancer Cooperative Group, Copenhagen, Denmark.
authors.forename: Maj-Britt
authors.initials: MB
authors.lastname: Jensen
authors.affiliation: Dako Denmark A/S, Glostrup, Denmark.
authors.forename: Kirsten V
authors.initials: KV
authors.lastname: Nielsen
authors.affiliation: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jørn
authors.initials: J
authors.lastname: Andersen
authors.affiliation: Department of Oncology, Herlev University Hospital, Herlev, Denmark.
authors.forename: Dorte
authors.initials: D
authors.lastname: Nielsen
authors.affiliation: Department of Oncology, Rigshospitalet, Copenhagen, Denmark; Danish Breast Cancer Cooperative Group, Copenhagen, Denmark.
authors.forename: Bent
authors.initials: B
authors.lastname: Ejlertsen
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D057194:Intention to Treat Analysis; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D017698:Postmenopause; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012307:Risk Factors; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; C508053:ERBB2 protein, human
keywords: Breast; Menopausal; Randomised adjuvant phase III trial; Subtypes; Tamoxifen