Estrogen Levels Linked to Breast Cancer Recurrence Risk

By Michael Smith
LA JOLLA, Calif., March 6 -- High estradiol levels in women who have been treated for early-stage breast cancer may increase the risk of recurrence, researchers here said.
Point out that this study cannot establish causality.
In a nested case-control study, women whose cancers recurred had double the total estradiol levels as did women who remained free of disease, according to Cheryl Rock, Ph.D., of the University of California, San Diego, and colleagues.
Although other factors contribute to breast cancer risk, the findings "provide evidence that higher serum estrogen concentration contributes to risk for recurrence," Dr. Rock and colleagues wrote in the March issue of Cancer Epidemiology, Biomarkers and Prevention.
"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," Dr. Rock said.
This study, larger than the others, was the first of its kind to include women taking agents such as tamoxifen to reduce estrogen's effect on cancer growth, she added.
Dr. Rock and colleagues evaluated 306 patients -- half with a recurrence -- from the Women's Healthy Eating and Living Study, a dietary intervention trial that followed 3,088 women who had been treated for early-stage breast cancer but who were cancer-free at the time they enrolled. (See: More Fruit and Vegetables No Better for Breast Cancer Survival)
Cases and controls were compared on the basis of baseline circulating concentrations of selected reproductive steroid hormones -- total, bioavailable, and free estradiol; total, bioavailable, and free testosterone; and sex hormone binding globulin.
The analysis found:
Testosterone and sex hormone binding globulin had no association with recurrence.
The serum concentration of total estradiol was associated with a 41% increase in risk for each unit increase in log concentration. The hazard ratio was 1.41, with a 95% confidence interval from 1.01 to 1.97, which was significant at P=0.04.
Similarly, bioavailable estradiol increased the risk by 26% for each unit increase in log concentration. The hazard ratio was 1.26, with a 95% confidence interval from 1.03 to 1.53, which was significant at P=0.02.
And free estradiol increased the risk by 31% for each unit increase in log concentration. The hazard ratio was 1.31, with a 95% confidence interval from 1.03 to 1.65, which was significant at P=0.03.
One implication of the finding, Dr. Rock said, is that women who have been treated for breast cancer "should do as much as they can to reduce estrogen in their blood."
Frequent exercise and keeping weight down are key interventions, she said, because anti-estrogen drugs, such as tamoxifen, "may not completely wipe out the hormone's effect in women who have high levels of estrogen."
The study was supported by the Walton Family Foundation, the National Cancer Institute, and the General Clinical Research Centers of the NIH. The researchers reported no conflicts.
Primary source: Cancer Epidemiology, Biomarkers and PreventionSource reference:Rock CL, et al "Reproductive steroid hormones and recurrence-free survival in women with a history of breast cancer" Cancer Epidemiol Biomarkers Prev 2008; 17(3): OF1-7.