title: Aromatase inhibitors, tamoxifen, and endometrial cancer in breast cancer survivors.
abstract: BACKGROUND
  The risks of both endometrial cancer and postmenopausal breast cancer are increased by obesity and higher endogenous estrogen levels. Although aromatase inhibitors reduce breast cancer incidence, their influence on endometrial cancer is uncertain.
  
  
  METHODS
  The authors investigated this issue in a cohort of 17,064 women who were diagnosed with hormone receptor-positive breast cancer in an integrated group practice health plan. Information on demographics, comorbidities, and the receipt of adjuvant endocrine therapy was available from electronic medical records and pharmacy records, respectively. Endometrial cancer information was obtained from the health plan's Surveillance, Epidemiology, and End Results-affiliated tumor registry, and rates were compared across endocrine therapy groups (aromatase inhibitor, n = 5303; tamoxifen, n = 5155; switchers: both [n = 3787] or none [n = 2819]) using multivariable adjusted Cox proportional-hazards models.
  
  
  RESULTS
  Endometrial cancer incidence was a statistically significant 48% lower in the aromatase inhibitor group versus the tamoxifen group (hazard ratio, 0.52; 95% confidence interval, 0.31-0.87; P = .01). Endometrial cancer incidence was 29% lower in the aromatase inhibitor group versus the no endocrine therapy group (hazard ratio, 0.71; 95% confidence interval, 0.37-1.35; P = .30) and 33% lower in the aromatase inhibitor group versus the tamoxifen group (hazard ratio, 0.67; 95% confidence interval, 0.42-1.06; P = .08), but neither difference was statistically significant. Associations were stronger among those with good drug adherence.
  
  
  CONCLUSIONS
  In a community-based, integrated health plan setting, endometrial cancer incidence was lower in women who were receiving an aromatase inhibitor compared with those who were receiving tamoxifen. In addition, aromatase inhibitors may mitigate the incidence of tamoxifen-associated endometrial cancer. Although there were somewhat fewer endometrial cancers in the aromatase inhibitor group versus the no endocrine therapy group, further studies are needed for the definitive assessment of this potential association.
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles, Torrance, California.
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.affiliation: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Schottinger
authors.affiliation: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California.
authors.forename: Jiaxiao
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California.
authors.forename: Joanie
authors.initials: J
authors.lastname: Chung
authors.affiliation: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California.
authors.forename: Reina
authors.initials: R
authors.lastname: Haque
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D047072:Aromatase Inhibitors / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002140:California / Q000453:epidemiology; D015331:Cohort Studies; D016889:Endometrial Neoplasms / Q000453:epidemiology* / Q000517:prevention & control; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D017741:Survivors / Q000706:statistics & numerical data; D013629:Tamoxifen / Q000008:administration & dosage*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D013629:Tamoxifen
keywords: aromatase inhibitors; breast cancer; chemoprevention; endometrial cancer; tamoxifen