Conjugated equine estrogen and risk of benign proliferative breast disease: A randomized controlled trial

Thomas E. Rohan, Abdissa Negassa, Rowan T. Chlebowski, Laurel Habel, Anne McTiernan, Mindy S. Ginsberg, Sylvia Wassertheil-Smoller, David L. Page

Research output: Contribution to journalArticle

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Abstract

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, 10739 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. Conclusion: Use of 0.625 mg/d of CEE was associated with a statistically significant increased risk of benign proliferative breast disease.

Original languageEnglish (US)
Pages (from-to)563-571
Number of pages9
JournalJournal of the National Cancer Institute
Volume100
Issue number8
DOIs
StatePublished - 2008

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Conjugated (USP) Estrogens
Breast Diseases
Randomized Controlled Trials
Confidence Intervals
Breast
Women's Health
Placebos
Proportional Hazards Models
Hyperplasia
Estrogens
Epithelium
Breast Neoplasms
Biopsy
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Conjugated equine estrogen and risk of benign proliferative breast disease : A randomized controlled trial. / Rohan, Thomas E.; Negassa, Abdissa; Chlebowski, Rowan T.; Habel, Laurel; McTiernan, Anne; Ginsberg, Mindy S.; Wassertheil-Smoller, Sylvia; Page, David L.

In: Journal of the National Cancer Institute, Vol. 100, No. 8, 2008, p. 563-571.

Research output: Contribution to journalArticle

Rohan, Thomas E. ; Negassa, Abdissa ; Chlebowski, Rowan T. ; Habel, Laurel ; McTiernan, Anne ; Ginsberg, Mindy S. ; Wassertheil-Smoller, Sylvia ; Page, David L. / Conjugated equine estrogen and risk of benign proliferative breast disease : A randomized controlled trial. In: Journal of the National Cancer Institute. 2008 ; Vol. 100, No. 8. pp. 563-571.
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abstract = "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, 10739 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. Conclusion: 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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AU - McTiernan, Anne

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AU - Wassertheil-Smoller, Sylvia

AU - Page, David L.

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N2 - 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, 10739 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. Conclusion: 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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