title: Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial.
abstract: BACKGROUND
  The Women's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks, including invasive breast cancer, exceeded benefits. Outstanding issues not previously addressed include characteristics of breast cancers observed among women using hormones and whether diagnosis may be influenced by hormone effects on mammography.
  
  
  OBJECTIVE
  To determine the relationship among estrogen plus progestin use, breast cancer characteristics, and mammography recommendations.
  
  
  METHODS
  Following a comprehensive breast cancer risk assessment, 16 608 postmenopausal women aged 50 to 79 years with an intact uterus were randomly assigned to receive combined conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo from 1993 to 1998 at 40 clinical centers. Screening mammography and clinical breast examinations were performed at baseline and yearly thereafter.
  
  
  METHODS
  Breast cancer number and characteristics, and frequency of abnormal mammograms by estrogen plus progestin exposure.
  
  
  RESULTS
  In intent-to-treat analyses, estrogen plus progestin increased total (245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001) and invasive (199 vs 150 cases; HR, 1.24; weighted P =.003) breast cancers compared with placebo. The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P =.04) and were at more advanced stage (regional/metastatic 25.4% vs 16.0%, respectively; P =.04) compared with those diagnosed in the placebo group. After 1 year, the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group (716 [9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001), a pattern which continued for the study duration.
  
  
  CONCLUSIONS
  Relatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms. These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis.
authors.affiliation: Harbor-UCLA Research and Education Institute, Torrance 90502, USA. rchlebowski@rei.edu
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.forename: Susan L
authors.initials: SL
authors.lastname: Hendrix
authors.forename: Robert D
authors.initials: RD
authors.lastname: Langer
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Stefanick
authors.forename: Margery
authors.initials: M
authors.lastname: Gass
authors.forename: Dorothy
authors.initials: D
authors.lastname: Lane
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Rodabough
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Gilligan
authors.forename: Michele G
authors.initials: MG
authors.lastname: Cyr
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Thomson
authors.forename: Janardan
authors.initials: J
authors.lastname: Khandekar
authors.forename: Helen
authors.initials: H
authors.lastname: Petrovitch
authors.forename: Anne
authors.initials: A
authors.lastname: McTiernan
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000453:epidemiology*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008327:Mammography; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009367:Neoplasm Staging; D017698:Postmenopause; D045167:Progesterone Congeners / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012306:Risk
chemical_list: D004966:Estrogens, Conjugated (USP); D045167:Progesterone Congeners; D017258:Medroxyprogesterone Acetate