title: Adjuvant tamoxifen reduces subsequent breast cancer in women with estrogen receptor-positive ductal carcinoma in situ: a study based on NSABP protocol B-24.
abstract: OBJECTIVE
  The NSABP (National Surgical Adjuvant Breast and Bowel Project) B-24 study demonstrated significant benefit with adjuvant tamoxifen in patients with ductal carcinoma in situ (DCIS) after lumpectomy and radiation. Patients were enrolled without knowledge of hormone receptor status. The current study retrospectively evaluated the relationship between receptors and response to tamoxifen.
  
  
  METHODS
  Estrogen (ER) and progesterone receptors (PgR) were evaluated in 732 patients with DCIS (41% of original study population). An experienced central laboratory determined receptor status in all patient cases with available paraffin blocks (n = 449) by immunohistochemistry (IHC) using comprehensively validated assays. Results for additional patients (n = 283) determined by various methods (primarily IHC) were available from enrolling institutions. Combined results were evaluated for benefit of tamoxifen by receptor status at 10 years and overall follow-up (median, 14.5 years).
  
  
  RESULTS
  ER was positive in 76% of patients. Patients with ER-positive DCIS treated with tamoxifen (v placebo) showed significant decreases in subsequent breast cancer at 10 years (hazard ratio [HR], 0.49; P < .001) and overall follow-up (HR, 0.60; P = .003), which remained significant in multivariable analysis (overall HR, 0.64; P = .003). Results were similar, but less significant, when subsequent ipsilateral and contralateral, invasive and noninvasive, breast cancers were considered separately. No significant benefit was observed in ER-negative DCIS. PgR and either receptor were positive in 66% and 79% of patients, respectively, and in general, neither was more predictive than ER alone.
  
  
  CONCLUSIONS
  Patients in NSABP B-24 with ER-positive DCIS receiving adjuvant tamoxifen after standard therapy showed significant reductions in subsequent breast cancer. The use of adjuvant tamoxifen should be considered for patients with DCIS.
authors.affiliation: National Surgical Adjuvant Breast and Bowel Project, Washington University School of Medicine, Department of Pathology and Immunology, 660 Euclid Campus Box 8118, St Louis, MO 63110, USA. dcallred@path.wustl.edu
authors.forename: D Craig
authors.initials: DC
authors.lastname: Allred
authors.forename: Stewart J
authors.initials: SJ
authors.lastname: Anderson
authors.forename: Soonmyung
authors.initials: S
authors.lastname: Paik
authors.forename: D Lawrence
authors.initials: DL
authors.lastname: Wickerham
authors.forename: Iris D
authors.initials: ID
authors.lastname: Nagtegaal
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Swain
authors.forename: Elefetherios P
authors.initials: EP
authors.lastname: Mamounas
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Julian
authors.forename: Charles E
authors.initials: CE
authors.lastname: Geyer
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Costantino
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Land
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002278:Carcinoma in Situ / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D015412:Mastectomy, Segmental / Q000379:methods; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000517:prevention & control*; D009367:Neoplasm Staging; D011960:Receptors, Estrogen / Q000032:analysis / Q000187:drug effects*; D011980:Receptors, Progesterone / Q000032:analysis / Q000187:drug effects; D018570:Risk Assessment; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage* / Q000009:adverse effects; D014481:United States
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen