Among women not using hormone therapy, obesity and the byproducts of estrogen breakdown appear to raise the risk of breast cancer, according to findings published in the International Journal of Cancer.

“Hormone therapy and body mass index (BMI) have been associated with postmenopausal breast cancer,” Dr. Francesmary Modugno, of the University of Pittsburgh, and colleagues write. “Because estrogen metabolism may affect breast cancer risk and can be altered by weight and hormone therapy, it might play a role in the hormone therapy-BMI-breast cancer associations.”

BMI is the ratio of body weight and height, and a score of 30 or higher is considered obese.

The researchers analyzed data from subjects enrolled in the Observational Study of the Women’s Health Initiative to examine relationships among obesity, hormone therapy, estrogen metabolism and breast cancer. They compared levels of two estrogen metabolic chemicals, 2-OHE1 and 16-alpha-OHE1, in 200 women who developed breast cancer and in 200 who did not.

In women who used hormone therapy, there was a modest but significant increase in 16-alpha-OHE1 and significantly higher 2-OHE1 levels in both groups. For these subjects, there was no association among BMI, estrogen metabolism and breast cancer risk.

For women who did not use hormone therapy, however, “greater BMI and higher 16-alpha-OHE1 were individually and jointly associated with increased cancer risk,” the investigators found. Compared with women with low BMI and low estrogen metabolite levels, those with a high BMI and high 16-alpha-OHE1 were 3.5-times more likely to develop breast cancer.

Estrogen metabolism is affected by both BMI and hormone therapy, the team concludes, “potentially explaining the interaction between BMI and hormone therapy in relation to breast cancer risk.”

SOURCE: International Journal of Cancer, March 2006.