Sex Hormones, Risk Factors, and Risk of Estrogen Receptor–Positive Breast Cancer in Older Women: A Long-term Prospective Study
- Steven R. Cummings1,
- Jennifer S. Lee1,
- Li-Yung Lui1,
- Katie Stone1,
- Britt Marie Ljung2,
- Jane A. Cauleys3 and
- for the Study of Osteoporotic Fractures Research Group
- 1San Francisco Coordinating Center, Research Institute at the California Pacific Medical Center; 2Department of Pathology, University of California, San Francisco, California; and 3Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania
- Requests for reprints:
Steven R. Cummings, California Pacific Medical Center, Coordinating Center, Suite 600, 74 New Montgomery Street, San Francisco, CA 94105. Phone: 415-597-9114; Fax: 415-597-9213. E-mail: Scummings{at}psg.ucsf.edu
Abstract
Objective: Antiestrogens reduce the risk of estrogen receptor–positive (ER+) but not ER-negative (ER−) breast cancer. Women at high risk of ER+ cancer would be the most likely to benefit from these treatments, but the best approach to predicting ER+ cancer is uncertain.
Methods: We prospectively assessed putative risk factors for breast cancer and archived serum at −190°C from a community-based cohort of 7,676 women ages ≥65 years who had no history of breast cancer. Follow-up for breast cancer over 10.5 years was 99% complete. Using a case-cohort design, we measured baseline levels of estradiol and testosterone in 196 cases of invasive ER+ cancer and 378 randomly selected controls.
Results: Women whose testosterone level in highest two quintiles had a 4-fold increased risk of ER+ breast cancer (P < 0.0001). High estradiol concentration also indicated an increased risk but was not a significant predictor after adjustment for testosterone. Women with >16 years of education had a 2.1 times increased risk (P = 0.03) of ER+ cancer, but no other risk factors were significantly related to an increased risk of ER+ cancer. Women with a family history of breast cancer had a 2.9-fold increased risk of ER− cancer (P = 0.002) but no increased risk of ER+ cancer (relative hazard = 1.2, 0.8-1.8).
Conclusions: High serum testosterone and advanced education predicted ER+ breast cancer. If confirmed, high testosterone level may be more accurate than family history of breast cancer and other conventional risk factors for identifying older women who are most likely to benefit from antiestrogen chemoprevention.
Footnotes
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Grant support: USPHS grants AG05407, AR35582, AG05394, AR35584, and AR35583 and Eli Lilly (analyses of sex hormones).
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Note: The company had no role in the design or analysis of the study or writing of the article.
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- Accepted January 5, 2005.
- Received May 17, 2004.
- Revision received December 10, 2004.
