An update of the results of the Study of Raloxifene and Tamoxifen, (STAR P-2 trial in breast cancer prevention) shows that the drug raloxifene (initially used to prevent and treat osteoporosis in postmenopausal women) improved its effectiveness against noninvasive breast cancer, caused significantly less endometrial cancer, and was significantly less toxic than tamoxifen. After 81 months of follow-up, although raloxifene was slightly less effective against invasive breast cancer, it still maintained strong efficacy.
The Reading Hospital and Medical Center (TRHMC) participated in the STAR Study, one of the largest breast cancer prevention clinical trials ever conducted. STAR enrolled 19,490 postmenopausal women who were at increased risk for the disease in the follow-up study. At TRHMC, 28 women were enrolled, and in Pennsylvania, 1,301 women were enrolled in the study. The Hospital’s first patient was enrolled in 1999.
This long-term trial is coordinated by the National Surgical Adjuvant Breast and Bowel Project (NSABP), a network of cancer research professionals, and is sponsored by the National Cancer Institute, part of the National Institutes of Health.
Participants were randomly assigned to receive either 60 mg of raloxifene (Evista®) (9,754 participants) or 20 mg of tamoxifen (Nolvadex®) (9,736 participants) daily. The 81-month study results (versus the 47 months in the initially published report) show that raloxifene retained 76% of the effectiveness in preventing invasive disease and grew closer to tamoxifen in preventing noninvasive disease, while remaining less toxic. The relative effects of the drugs in the longer term are more consistent with expected profiles, including greater potency of tamoxifen in preventing invasive and noninvasive disease, and, significantly, less endometrial toxicity with raloxifene.
Improved detection and treatment of breast cancer have not eliminated the need for better prevention of this disease, which accounted for approximately 192,000 new cancer cases and 40,000 cancer deaths in the U.S. in 2009. Although the selective estrogen-receptor modulator (SERM) tamoxifen became the first U.S. Food and Drug Administration (FDA) approved agent for reducing breast cancer risk, it did not gain wide acceptance for prevention largely because it increased endometrial cancer and thromboembolic events. Raloxifene was approved by the FDA for breast cancer risk reduction following its pronounced efficacy in preventing invasive, but not noninvasive, breast cancer in the Phase III Study of Tamoxifen and Raloxifene . Initial STAR toxicity profiles favored raloxifene (e.g. significantly reduced thromboembolic events and, non-significantly, reduced endometrial cancer) over tamoxifen. Differences in the two drugs made it imperative to conduct longer-term follow-up to clarify their relative merits in regard to a host of benefits and risks, but particularly in regard to noninvasive breast cancer.
STAR participants were postmenopausal, at least 35-years old, and had a modified breast cancer risk as determined by their age, family history of breast cancer, personal medical history, age of first menstrual period, and age at first live birth. Eligible women were randomly assigned to receive either tamoxifen or raloxifene daily for five years. Before participating in the Study, women were instructed about the potential risks and benefits of tamoxifen and raloxifene, and then were asked to sign an informed consent document.