Predictive risk models, such as the Gail model, have been widely used by clinicians to help determine a woman’s risk of breast cancer and to help inform decisions on the use of chemoprevention.  While circulating sex steroid hormones have been consistently associated with breast cancer risk among postmenopausal women, most studies of the hormone-breast cancer association have been conducted among women at average risk of breast cancer, not in high-risk populations.  Although the predictive models incorporate many hormonally-related risk factors, such as reproductive history, neither the Gail nor the Rosner/Colditz predictive models includes hormone levels.  Thus, we calculated 5-year predicted risk among women in the Nurses’ Health Study using both the Gail and Rosner/Colditz models and examined the associations of estrogens and testosterone with breast cancer risk in a nested case-control study.  Although these women were at average risk overall, we categorized women by low and high predicted risk.  We found that estradiol, estrone sulfate, and testosterone levels were significantly associated with the risk of breast cancer, regardless of a woman’s predicted risk or family history of breast cancer.  Thus, circulating hormone levels may be important to consider when evaluating a woman’s risk of breast cancer, even among women who are at higher predicted risk.

 

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