Postmenopausal women with high amounts of estrogen and testosterone in their bloodstream may be at more than twice the risk of developing breast cancer as those with low levels of the hormones, according to a study by British researchers published in the Journal of the National Cancer Institute.

Testing for sex hormones may ultimately lead to useful ways of predicting a woman's risk, wrote scientists from the Cancer Research UK Epidemiology Unit in Oxford, while learning more about the causes of breast cancer may bring new ways of preventing the disease. And since obesity is the biggest known reason for high levels of sex hormones among postmenopausal women, they suggest that maintaining a healthy weight could help women bring down their breast cancer risk.

The researchers pooled together data from nine separate studies carried out in the UK, US, Italy and Japan, and including a total of 1765 healthy women and 663 with breast cancer.

In each study, blood samples were taken from postmenopausal women, levels of sex hormones were measured, and the women were followed for a number of years to see who developed breast cancer. By combining the results from all nine studies, the scientists were able for the first time to reliably estimate the effect of postmenopausal hormone levels on breast cancer risk.

For each of the hormones tested, the researchers compared one fifth of the women with the highest blood levels to the fifth with the lowest. They found that high levels of free estradiol - an active form of estrogen - more than doubled the risk of breast cancer compared with women who had low levels of the hormone. Those with high levels of testosterone were also at more than twice the risk.

The study also found that women with raised levels of a molecule called sex hormone binding globulin, which reduces the activity of sex hormones, were at lower than usual risk. Interestingly, women who are obese have low levels of this molecule, which probably also helps to raise their risk of breast cancer.

"We've known for some time that reproductive and hormonal factors were involved in the development of breast cancer. But until now, we haven't had strong evidence for a direct link between the blood levels of 'natural' hormones and risk of the disease. Our study confirms that high levels of sex hormones can raise risk," said Dr. Tim Key, the study leader.

"In the future, our research may allow testing to predict a woman's risk of breast cancer and could provide leads for improved drugs to help prevent the disease. But meanwhile it's important that women try to maintain a healthy weight, since this will reduce their blood estrogen levels and breast cancer risk."

SOURCES:
Journal of the National Cancer Institute, April 17, 2002; 94(8)
Cancer Research UK (http://www.cancerresearchuk.org)