RUTH. Raloxifene Use and the Heart (RUTH) is a double-blind, placebo-controlled trial of 60 mg of raloxifene that will include 10,000 women. Primary endpoints are coronary disease and invasive breast cancer. Trial enrollment ended in August 2000, and the study is expected to conclude in 2006.
Aromatase inhibitors: Another route of prevention
The evidence that estrogens facilitate breast cancer development in animals and women is substantial, although the precise mechanism is unknown.17 The most commonly held theory is that estrogen stimulates proliferation of breast cells. Thus, it statistically increases the chances for genetic mutations that could result in cancer.
Aromatase inhibitors block peripheral conversion of androstenedione to estrogens. In premenopausal patients, the primary site of this action is in the ovary. In post-menopausal women, it occurs predominantly in extraovarian sites, including the adrenal glands, adipose tissue, liver, muscle, and skin.
Because of their dual role, (blocking both the initiation and promotion of breast cancer), aromatase inhibitors may be more effective than SERMs in preventing breast cancer.18 By inhibiting the initiation process, they would reduce levels of genotoxic metabolites of estradiol by lowering estradiol concentration in tissue. They also would inhibit tumor promotion by lowering tissue levels of estradiol—thus blocking cell proliferation. However, because they are not selective, aromatase inhibitors would have an antiestrogen effect on bone and lipid metabolism and would induce vasomotor symptoms.
Dr. Goldstein serves on gynecology advisory boards for Eli Lilly and Company, Pfizer, AstraZeneca, and P&G Pharmaceuticals.