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Elevated Serum Estradiol and Testosterone Concentrations Are Associated with a High Risk for Breast Cancer

Jane A. Cauley, DrPH; Frances L. Lucas, PhD; Lewis H. Kuller, MD, DrPH; Katie Stone, PhD; Warren Browner, MD, MPH; Steven R. Cummings, MD, for the Study of Osteoporotic Fractures Research Group
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From University of Pittsburgh, Pittsburgh, Pennsylvania; Maine Medical Center, Portland, Maine; University of California, San Francisco; and Veterans Affairs Medical Center, San Francisco, California.

Ann Intern Med. 1999;130(4_Part_1):270-277. doi:10.7326/0003-4819-130-4_Part_1-199902160-00004
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Background: The relation between endogenous steroid hormones and risk for breast cancer is uncertain. Measurement of sex hormone levels may identify women at high risk for breast cancer who should consider preventive therapies.

Objective: To test the hypothesis that serum concentrations of estradiol and testosterone predict risk for breast cancer.

Design: Prospective case-cohort study.

Setting: Four clinical centers in the United States.

Participants: 97 women with confirmed incident breast cancer and 244 randomly selected controls; all women were white, 65 years of age or older, and were not receiving estrogen.

Measurements: Sex-steroid hormone concentrations were assayed by using serum that was collected at baseline and stored at −190 °C. Risk factors for breast cancer were ascertained by questionnaire. Incident cases of breast cancer were confirmed by review of medical records during an average period of 3.2 years.

Results: The relative risk for breast cancer in women with the highest concentration of bioavailable estradiol (≥ 6.83 pmol/L or 1.9 pg/mL) was 3.6 (95% CI, 1.3 to 10.0) compared with women with the lowest concentration. The risk for breast cancer in women with the highest concentration of free testosterone compared with those with the lowest concentration was 3.3 (CI, 1.1 to 10.3). The estimated incidence of breast cancer per 1000 person-years was 0.4 (CI, 0.0 to 1.3) in women with the lowest levels of bioavailable estradiol and free testosterone compared with 6.5 (CI, 2.7 to 10.3) in women with the highest concentrations of these hormones. Traditional risk factors for breast cancer were similar in case-patients and controls. Adjustments for these risk factors had little effect on the results.

Conclusions: Estradiol and testosterone levels may play important roles in the development of breast cancer in older women. A single measurement of bioavailable estradiol and free testosterone may be used to estimate a woman's risk for breast cancer. Women identified as being at high risk for breast cancer as determined by these hormone levels may benefit from antiestrogen treatment for primary prevention.


Grahic Jump Location
Incidence of breast cancer (95% CI) in relation to concentrations of bioavailable estradiol and free testosterone.

Incidence expressed per 1000 person-years. Quartile 1: free testosterone, up-slanting diagonally striped bar; quartiles 2 and 3: free testosterone, white bar; quartile 4: free testosterone, down-slanting diagonally striped bar.

Grahic Jump Location




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