title: Estimation of tamoxifen's efficacy for preventing the formation and growth of breast tumors.
abstract: BACKGROUND
  Several randomized clinical trials have tested the hypothesis that tamoxifen is effective in preventing breast cancer. The largest such trial, the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention Trial (BCPT), reported a 49% reduction in risk of invasive breast cancer for the tamoxifen group. However, it is unclear whether the effect of tamoxifen in this trial was mainly due to prevention of newly forming tumors or to treatment of occult disease.
  
  
  METHODS
  We used various tumor growth models (i.e., exponential and Gompertzian [growth limited by tumor size]) and a computer simulation to approximate the percentage of detected tumors that were initiated after study entry. Maximum likelihood techniques were then used to estimate separately the efficacy of tamoxifen in treating occult disease and in preventing the formation and growth of new tumors.
  
  
  RESULTS
  Under the assumptions of most of the growth models, the trial was sufficiently long for substantial numbers of new tumors to form, grow, and be detected during the trial. With the Gompertzian model and all available incidence data from the BCPT, it was estimated that 60% (95% confidence interval [CI] = 40%-80%) fewer new tumors were detected in the tamoxifen group than in the placebo group. Likewise, 35% (95% CI = 6%-63%) fewer occult tumors were detected in the tamoxifen group. With this model, the estimated incidence rate of invasive breast cancer among women in the placebo group of the BCPT was 7.7 (95% CI = 6.6-8.9) per 1000 women per year. Similar results were obtained with three exponential tumor growth models.
  
  
  CONCLUSIONS
  These results support the concept that tamoxifen reduced cancer incidence in the BCPT through both treatment of occult disease and prevention of new tumor formation and growth. However, data from prevention trials may never be sufficient to completely distinguish prevention of new tumor formation from treatment of occult disease.
authors.affiliation: Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA. mdradmac@helix.nih.gov
authors.forename: M D
authors.initials: MD
authors.lastname: Radmacher
authors.forename: R
authors.initials: R
authors.lastname: Simon
mesh_terms: D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000517:prevention & control*; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D016588:Anticarcinogenic Agents; D018931:Antineoplastic Agents, Hormonal; D020847:Estrogen Receptor Modulators; D013629:Tamoxifen