BETHESDA, MarylandRaloxifene (Evista, Eli Lilly) has proven as effective as tamoxifen in reducing the risk of invasive breast cancer in postmenopausal women who are at increased risk of the disease. Initial findings from the Study of Tamoxifen and Raloxifene (STAR) showed that both drugs reduced breast cancer risk by about 50% but that patients in the raloxifene arm had 36% fewer uterine cancers and 29% fewer blood clots than those on tamoxifen.
"These results demonstrate that raloxifene is an effective alternative to tamoxifen for preventing invasive breast cancer, and with fewer life-threatening side effects," D. Lawrence Wickerham, MD, told ONI in an interview. Dr. Wickerham serves as the STAR protocol officer and associate chairman of the National Surgical Adjuvant Breast and Bowel Project (NSABP), which coordinated the National Cancer Institute-supported trial.
In 1998, results from the Breast Cancer Prevention Trial, a study of more than 13,000 women, showed that tamoxifen could cut the risk of breast cancer by half in both pre- and postmenopausal women at elevated risk of the disease. However, this preventive treatment carried with it a low but real risk of potentially fatal adverse events, particularly stroke and uterine cancer.
By then, clinical reports suggested that raloxifene, a drug now approved for use in preventing and treating osteoporosis in postmenopausal women, could also reduce the risk of developing breast cancer, and with fewer side effects. As a result, NCI decided to sponsor a trial to compare the two drugs.
STAR is a prospective, randomized, double-blind study that enrolled its first patients in July 1999, and eventually accrued 19,747 women at more than 400 sites in the United States, Puerto Rico, and Canada. Its protocol required participants to be postmenopausal, at least age 35, and have an increased risk of breast cancer as determined by their age, family history of breast cancer, personal medical history, age of first menstrual period, and age at first live birth. Exclusion criteria included a history of blood clots and other disorders that increase the risk of stroke.
Participants were randomized to receive 60 mg of raloxifene or 20 mg of tamoxifen daily for 5 years. Results were based on data from the 19,471 women for whom researchers had complete study information9,745 in the raloxifene arm and 9,726 in the tamoxifen group. Patient follow-up was a mean of 4 years. The STAR findings were released by NSABP and NCI officials during a teleconference with members of the media.
The results showed that a statistically equivalent number of invasive breast cancers developed in the two groups of women167 in the raloxifene arm and 163 in the tamoxifen group. Previous studies have shown that tamoxifen reduces by half the incidence of lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS). However, the women receiving raloxifene did not reap the same benefit: 57 women in the tamoxifen group developed LCIS or DCIS vs 81 in the raloxifene arm.