Initial results of the Study of Tamoxifen and Raloxifene (STAR), one of the largest breast cancer prevention trials ever conducted (nearly 20,000 participants), show that the anti-osteoporosis drug raloxifene works as well as tamoxifen in reducing breast cancer risk for postmenopausal women who are at increased risk of the disease. In 2006, more than 212,000 women will be diagnosed with breast cancer, most of them postmenopausal, and over 40,000 will die of their disease.
"Today, we can tell you that for postmenopausal women at increased risk of breast cancer, raloxifene is just as effective, without some of the serious side effects known to occur with tamoxifen," said Norman Wolmark, MD, chairman of the National Surgical Adjuvant Breast and Bowel Project (NSABP), in April 2006, when the results were released. NSABP, a network of cancer research professionals, coordinated the study, which is sponsored by the National Cancer Institute (NCI).
Both drugs reduced the risk of developing invasive breast cancer by about 50%. However, women who took raloxifene daily for an average of about four years had 36% fewer uterine cancers and 29% fewer blood clots than those who took tamoxifen. Uterine cancers, especially endometrial cancers, are a rare but serious side effect of tamoxifen. Both tamoxifen and raloxifene are known to increase a woman's risk of blood clots. In addition, although tamoxifen has been shown to reduce by half the incidence of noninvasive breast cancers, lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS), raloxifene did not have an effect on these diagnoses.
Women taking either drug had equivalent numbers of strokes, heart attacks, and bone fractures. Menopausal side effects of both drugs were mild to moderate in severity, and quality of life was the same for both. More than half of the women in STAR had had a hysterectomy, and therefore were not at risk of uterine cancer. Both drugs are known to protect bone health; it is estimated that half a million postmenopausal women are currently taking raloxifene in order to either prevent or treat osteoporosis. The STAR results also suggest that raloxifene does not increase the risk of developing a cataract, as tamoxifen does.
The STAR results show that raloxifene represents an effective alternative for postmenopausal women at increased risk of breast cancer, according to D. Lawrence Wickerham, MD, associate NSABP chairman. "Tamoxifen is still an incredibly effective drug and it's the only drug currently approved for breast cancer chemoprevention, and that includes in premenopausal women. The discussion about whether women should switch to raloxifene needs to be between each patient and her doctor," he noted.
Leslie Ford, MD, associate director for clinical research in NCI's Division of Cancer Prevention, said the trial’s outcomes will make breast cancer prevention more of a reality for many women. "Although no drugs are without side effects, tamoxifen and raloxifene are vital options for women who are at increased risk of breast cancer and want to take action. For many women, raloxifene's benefits will outweigh its risks in a way that tamoxifen's benefits do not," she declared.
Participants Notified of Results and Options
At the start of the trial, NSABP committed to notify the participants of any major results as soon as possible. Information to each participant telling her which drug she was taking, was made available April 17, 2006 to the STAR investigators to convey. All the women are being asked to continue their follow-up examinations according to the study protocol. Women who were randomly assigned to the raloxifene group and who have not completed five years of therapy will be able to continue on that drug. Women who were randomly assigned to the tamoxifen group have the option of completing their five years of tamoxifen or switching to raloxifene for the remainder of their five years. Raloxifene has not been approved by the Food and Drug Administration (FDA) for use in breast cancer chemoprevention, but the drug's manufacturer, Eli Lilly and Company, Indianapolis, Ind., has said it would request the agency's approval to market raloxifene for the prevention of invasive breast cancer in postmenopausal women.
Using STAR as a START…
In addition to large-scale clinical trials such as STAR, the NCI is undertaking several smaller studies in populations with elevated breast cancer risk in order to pursue specific research issues. These high-risk populations may be given an agent for weeks to years; blood and tissue samples are taken before and after the intervention to search for biomarker endpoints. Pharmaceutical agents under study in such trials include exemestane (an aromatase inhibitor), acolbifene (a selective estrogen receptor modulator), bexarotene (a rexanoid), and celecoxib and sulindac (anti-inflammatory drugs). Dietary agents being studied include soy isoflavones , polyphenone E (a green tea component), and Brevail (derived from flax seed).
