Increased Risk of Breast Cancer Recurrence Tied To High Levels of Estrogen

Women whose breast cancer returned after treatment had almost twice as much estrogen in their blood than did women who remained cancer-free, according to a newly published study.

The study’s lead author, Cheryl L. Rock, Ph.D., a professor in the Department of Family and Preventive Medicine at the University of California, San Diego, said that high levels of estrogen—which lead to the initial development of breast cancer—could be associated with an increased risk of recurring cancer.

"While this makes sense, there have been only a few small studies that have looked at the link between sex hormones in the blood and cancer recurrence," she said. "This is the largest study to date and the only one to have included women taking agents such as tamoxifen to reduce estrogen’s effect on cancer growth."

"What the results mean for women who have already been treated for breast cancer is that they should do as much as they can to reduce estrogen in their blood, such as exercising frequently and keeping weight down," she added. "Taking anti-estrogen drugs like tamoxifen may not completely wipe out the hormone’s effect in women who have high levels of estrogen."

The Women’s Healthy Eating and Living Study (WHEL) provided participants for the breast cancer study, a dietary intervention trial that monitored 3,088 women treated for breast cancer but cancer-free when recruited for the study. Subjects were placed in two groups—one that ate a " normal" healthy diet, one that ate extremely large amounts of fruits, fiber and vegetables. After 7 years, participants were checked for breast cancer, which was about the same for each group. Researchers interpreted the findings to mean that a normal diet that incorporates the U.S. Food and Drug Administration guidelines for recommended amounts of fruits and vegetables is sufficient.

In the current study, 153 WHEL participants whose cancer had recurred were matched with 153 participants who remained cancer-free. These pairs were alike in terms of tumor type, body size, age, ethnicity, use of chemotherapy and other variables. Two-thirds of the participants were using tamoxifen, Rock said.

When they enrolled, researchers tested the women’s blood for concentrations of the steroid hormones estradiol (the primary human estrogen) and testosterone. They analyzed different forms of estradiol and testosterone in the blood, such as how much was bound to transport proteins (such as to the sex hormone binding globulin, or SHBG) and how much was "free" circulating and able to enter a cell.

The study was published in the March issue of Cancer Epidemiology, Biomarkers and Prevention, a journal of the American Association for Cancer Research.