Estrogen level determines osteoporosis drug's breast cancer prevention effectiveness in postmenopaus

By Eve Harris

A common osteoporosis drug can reduce breast cancer in postmenopausal women with high estrogen levels, but produces no reduction in risk for women whose estrogen levels are very low, according to a UCSF study. Researchers found that raloxifene administered to a selected population of women reduced their rate of breast cancer by 76 percent. The study was published in the January 9 issue of the Journal of the American Medical Association (JAMA).
The authors studied 7290 postmenopausal women aged 80 or younger with osteoporosis and no history of breast cancer. Study participants were given either the recommended daily 60 mg dose, a 120 mg dose, or a placebo. Their blood was screened for estradiol - the most potent form of estrogen. Women with levels in the upper third of the range for the tested group were shown to be at high risk of breast cancer and benefit most from raloxifene at any dosage.

According to the authors, previous studies have found that the risk of breast cancer rises with increases in a woman’s estrogen level. In some breast cancers, proteins on the malignant cells have a receptor that locks to estrogen molecules. Drugs like raloxifene block the effect of estrogen in the breast. The authors therefore postulated that the success of drugs like raloxifene, called selective estrogen receptor modulators (SERMs), in preventing breast cancer is likely to depend on a woman’s level of estrogen. With little or no circulating estrogen to feed breast cancer cells, a woman is already at reduced risk, without treatment with SERMs.

“Measuring estradiol and treating those postmenopausal women who have high levels could substantially reduce their rate of breast cancer,” said Steven R. Cummings, MD, UCSF Professor professor of Medicine medicine and Epidemiology epidemiology and Biostatistics biostatistics and Director, UCSF Clinical Research Program.

To test their hypothesis, Cummings and his co-authors examined data compiled in their concluded study of raloxifene, the Multiple Outcomes of Raloxifene Evaluation (MORE) study, funded by the drug’s producer, Eli Lilly and Company.  MORE was designed to test the drug’s efficacy in reducing the risk of vertebral fracture in women with osteoporosis. Of the 7705 women from 177 sites around the world who were enrolled in MORE, 7290 had their level of estradiol tested at MORE’s inception. That group was followed for four years to determine how many breast cancers developed and in whom.

“Sensitive testing of the sort used in this study is not yet widely available for clinical use,” said Cummings. SciCor (Covance) Central Laboratory Services performed all the blood tests for this study using a very sensitive assay. “Measuring estrogen to determine breast cancer risk may help identify women likely to experience the greatest reduction in breast cancer from treatment with raloxifene. But if sensitive measurements of estrogen are used to make treatment decisions in the future, it will be important to standardize the methods,” he said.

Raloxifene is currently prescribed to reduce osteoporosis, the loss of bone density that affects about 23 percent of American women over the age of 50. It is not FDA approved for the prevention of breast cancer. Breast cancer is the most common malignancy in women. The risk increases with advancing age—1 in 54 by age 50 and 1 in 23 by age 60 (National Cancer Institute, 2000).
Other authors of the study are Tu Duong, MA, UCSF Coordinating Center Statistician; Emily Kenyon, PhD, UCSF Associate Specialist in Epidemiology; Jane A. Cauley, DrPH, University of Pittsburgh Department of Epidemiology, Graduate School of Public Health; Malcolm Whitehead, MS, BS, FRCOG, Consultant Gynaecologist, Kings College Hospital, London; and Kathryn A. Krueger, MD, Eli Lilly and Company Clinical Research Physician.