Estrogen plus progestin and risk of benign proliferative breast disease.

Abstract

Women with benign proliferative breast disease are at increased risk of subsequent breast cancer. Estrogens and progesterone exert proliferative effects on mammary epithelium, and combined hormone replacement therapy has been associated with increased breast cancer risk. We tested the effect of conjugated equine estrogen plus progestin on the risk of benign proliferative breast disease in the Women's Health Initiative (WHI) randomized controlled trial. In the WHI trial of estrogen plus progestin, 16,608 postmenopausal women were randomly assigned either to 0.625 mg/day of conjugated equine estrogen plus 2.5 mg/day of medroxyprogesterone acetate or to placebo. Baseline and annual breast exams and mammograms were required. The trial was terminated early (average follow-up, 5.5 years). We identified women who had had a biopsy for benign breast disease, and subjected histologic sections from the biopsies to standardized review. Overall, 178 incident cases of benign proliferative breast disease were ascertained in the estrogen plus progestin group and 99 in the placebo group. The use of estrogen plus progestin was associated with a 74% increase in the risk of benign proliferative breast disease [hazard ratio, 1.74; 95% confidence interval (CI), 1.35-2.25]. For benign proliferative breast disease without atypia the hazard ratio was 2.00 (95% CI, 1.50-2.66), while for atypical hyperplasia it was 0.76 (95% CI, 0.38-1.52). The risk varied little by levels of baseline characteristics. The results of this study suggest that the use of estrogen plus progestin may increase the risk of benign proliferative breast disease.

• Authors: Thomas E Rohan, Abdissa Negassa, Rowan T Chlebowski, Norman L Lasser, Anne McTiernan, Robert S Schenken, Mindy Ginsberg, Sylvia Wassertheil-Smoller, David L Page
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 17 Issue 9 Pg. 2337-43 (Sep 2008) ISSN: 1055-9965 [Print] United States
• PMID: 18725513 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Estrogens
• Progestins

Topics

• Aged
• Biopsy
• Breast Diseases (chemically induced, diagnosis, epidemiology)
• Estrogen Replacement Therapy (adverse effects)
• Estrogens (administration & dosage, adverse effects)
• Female
• Humans
• Hyperplasia (chemically induced, diagnosis, epidemiology)
• Incidence
• Mammography
• Middle Aged
• Postmenopause
• Precancerous Conditions (chemically induced, diagnosis, epidemiology)
• Progestins (administration & dosage, adverse effects)
• Proportional Hazards Models
• Risk
• United States (epidemiology)