Conjugated Equine Estrogen and Risk of Benign Proliferative Breast Disease: A Randomized Controlled Trial

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.
Journal of the National Cancer Institute (Impact Factor: 12.58). 05/2008; 100(8):563-71. DOI: 10.1093/jnci/djn075
Source: PubMed


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.
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.
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.
Use of 0.625 mg/d of CEE was associated with a statistically significant increased risk of benign proliferative breast disease.

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    • "Estrogen has physiological effects of cell proliferation and differentiation during the cell cycle. Probably in benign proliferative breast disease the steroid hormones antagonizes cell differentiation and apotosis [21,22]. The normal proliferation of cells due to action of endogenous steroid hormones leads to the breast enlargement seen at puberty and the reproductive period. "
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    ABSTRACT: Background Non-cancerous diseases of the breast have assumed increasing importance because of the public awareness of breast cancer. These benign diseases are a recognized important risk factor for later breast cancer which can develop in either breast. The risk estimate of these benign breast diseases has not been well established in sub Saharan Africa. Women with benign proliferative or atypical breast lesions have a two- fold risk of developing breast cancer in western populations. The purpose of this study therefore was to determine the prevalence of proliferative disease ( BPBD) with and without atypia among Ugandan Black women. Methods A cross-sectional descriptive study conducted at Mulago Hospital Breast Clinic between January 2012 and June 2012; 208 women aged 12 years and above with palpable breast lumps were screened. Fine needle aspiration biopsies were taken for cytological examination. Results Of the 208 women with benign breast lumps screened, 195 were recruited in the study. The prevalence of BPBD was 18% (35/195). BPBD with atypia was 5.6% (11/195). The mean age and body mass index (BMI) were 28.4 years and 23.26 kg/m2 respectively. The commonest lesions were fibroadenomas for 57%, (111/195), and fibrocystic change were 21% (40/195). Most BPBD with atypia lesions were in the fibrocystic category. Conclusions Benign proliferative breast diseases are common, found mostly among premenopausal women. A significant proportion of BPBD had atypical proliferation. An accurate breast cancer risk estimate study for BPBD is recommended.
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    • "While not related to endogenous hormones, recent observations also support a role for reproductive hormone influence on BBD. In the Women's Health Initiative randomised, placebo-controlled hormone therapy trials, conjugated equine oestrogen resulted in a statistically significant increase in BBD (Rohan et al, 2008). "
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