Conjugated equine estrogen and risk of benign proliferative breast disease: a randomized controlled trial.
BACKGROUND
Estrogens stimulate proliferation of breast epithelium and may therefore increase the risk of benign proliferative breast disease, a condition that is associated with increased risk of breast cancer. We tested the effect of conjugated equine estrogen (CEE) on risk of benign proliferative breast disease in the Women's Health Initiative (WHI) randomized controlled trial.


METHODS
In the WHI CEE trial, 10,739 postmenopausal women were randomly assigned to 0.625 mg/d of CEE or to placebo. Baseline and annual breast examinations and mammograms were required. We identified women in the trial who reported breast biopsies that were free of cancer, obtained the associated histological sections, and subjected them to standardized central review. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided.


RESULTS
A total of 232 incident cases of benign proliferative breast disease were ascertained during follow-up (average duration, 6.9 years), with 155 in the CEE group and 77 in the placebo group. Use of CEE was associated with a more than two-fold increase in the risk of benign proliferative breast disease (HR = 2.11, 95% CI = 1.58 to 2.81). For benign proliferative breast disease without atypia, the HR was 2.34 (95% CI = 1.71 to 3.20), whereas for atypical hyperplasia, it was 1.12 (95% CI = 0.53 to 2.40). Risk varied little by levels of baseline characteristics.


CONCLUSIONS
Use of 0.625 mg/d of CEE was associated with a statistically significant increased risk of benign proliferative breast disease.
Rohan
Thomas E
TE
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA. rohan@aecom.yu.edu
Negassa
Abdissa
A
Chlebowski
Rowan T
RT
Habel
Laurel
L
McTiernan
Anne
A
Ginsberg
Mindy
M
Wassertheil-Smoller
Sylvia
S
Page
David L
DL
D000368:Aged; D001706:Biopsy; D001941:Breast Diseases / Q000139:chemically induced* / Q000473:pathology*; D001943:Breast Neoplasms / Q000139:chemically induced / Q000473:pathology; D016001:Confidence Intervals; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006965:Hyperplasia / Q000139:chemically induced; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D016017:Odds Ratio; D017698:Postmenopause; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology; D016016:Proportional Hazards Models; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors
D004966:Estrogens, Conjugated (USP)