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Postoophorectomy Estrogen Use and Breast Cancer Risk

Nichols, Hazel B. PhD; Trentham-Dietz, Amy PhD; Newcomb, Polly A. PhD; Titus, Linda J. PhD; Egan, Kathleen M. ScD; Hampton, John M. MS; Visvanathan, Kala MBBS, MHS

doi: 10.1097/AOG.0b013e31825a717b
Original Research

OBJECTIVE: To estimate whether the protective effect of premenopausal bilateral oophorectomy on breast cancer risk is mitigated by estrogen therapy use after surgery.

METHODS: In pooled data from four population-based case–control studies spanning 1992–2007, we examined estrogen use after total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAHBSO) and subsequent breast cancer risk. We identified cases of postmenopausal invasive breast cancer in women (n=10,449) aged 50–79 years from three state tumor registries and age-matched control group participants without breast cancer (n=11,787) from driver's license and Medicare lists. Total abdominal hysterectomy with bilateral salpingo-oophorectomy and estrogen use were queried during structured telephone interviews. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with multivariable logistic regression.

RESULTS: Breast cancer risk comparisons were made relative to women who experienced natural menopause and never used hormones. Overall, breast cancer risk increased 14% among women currently using estrogens after TAHBSO (OR 1.14, 95% CI 1.03–1.28), 32% for estrogen durations less than 10 years (OR 1.32, 95% CI 1.11–1.57), and 22% for estrogen initiation within 5 years of TAHBSO (OR 1.22, 95% CI 1.09–1.37). Among women who underwent early TAHBSO (younger than 40 years), 24–30% decreases in breast cancer risk were observed among both never (OR 0.70, 95% CI 0.55–0.88) and current (OR 0.76, 95% CI 0.61–0.96) estrogen users.

CONCLUSION: Unopposed estrogen use does not negate the reduction in breast cancer risk associated with early (younger than 40 years) bilateral oophorectomy. However, initiating estrogen therapy after TAHBSO at ages 45 and older can increase breast cancer risk and should be considered carefully.


Bilateral oophorectomy before age 40 reduces breast cancer risk regardless of estrogen use. At older ages, estrogen use after surgery may increase breast cancer risk.

From the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland; the Department of Population Health Sciences, and the Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin, Madison, Wisconsin; the Fred Hutchinson Cancer Research Center, Seattle, Washington; Dartmouth Medical School, Lebanon, New Hampshire; and the H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.

Supported by grants from the National Cancer Institute at the National Institutes of Health (CA47147, CA47305, CA069664, CA009314, CA111948).

Corresponding author: Hazel B. Nichols, National Institute of Environmental Health Sciences, P.O. Box 12233, MD A3-05, 111 T. W. Alexander Drive, Research Triangle Park, NC 27709; e-mail:

Financial Disclosure The authors did not report any potential conflicts of interest.

© 2012 The American College of Obstetricians and Gynecologists