From OncoLog, May 2006, Vol. 51, No. 5

Raloxifene Effective for Breast Cancer Prevention: Osteoporosis Drug Edges Past Tamoxifen in National STAR Trial

by Kathryn Carnes

A new option for breast cancer prevention may soon be available to physicians and their patients. In a huge multi-center study, raloxifene (Evista), a common osteoporosis drug, was shown to be as effective as tamoxifen (Nolvadex) in preventing invasive breast cancer but had fewer side effects.

The much-anticipated results were from an initial analysis of data from the Study of Tamoxifen and Raloxifene (STAR). STAR is a clinical trial designed to compare the two drugs’ abilities to reduce the incidence of breast cancer in postmenopausal women at increased risk for developing the disease. This study, which accrued almost 20,000 women between July 1999 and November 2004, is a project of the National Surgical Adjuvant Breast and Bowel Project (NSABP). Major funding for the trial is provided by the National Cancer Institute (NCI).

Houston-based The University of Texas M. D. Anderson Cancer Center enrolled more than 400 STAR participants. Among the 195 participating clinical cancer centers, M. D. Anderson Cancer Center ranked second in overall accrual and third in the enrollment of minority women, after Puerto Rico and Hawaii.

Both raloxifene and tamoxifen were equivalent in reducing the incidence of invasive breast cancer in postmenopausal women at increased risk for the disease by about 50% compared with the expected incidence based on historical data (the STAR trial did not include a control arm).

But perhaps more exciting, researchers said, is that raloxifene (given at a dose of 60 mg once a day) achieved this level of efficacy while conferring a lower incidence of side effects than tamoxifen (given at a dose of 20 mg once a day). “When you are talking about prevention, particularly when you are asking women to take a drug for 5 years of their lives, the side effect profile becomes very important,” said Therese Bevers, M.D. Dr. Bevers is the medical director of M. D. Anderson’s Cancer Prevention Center and served as the institution’s principal investigator for STAR.

Tamoxifen, a selective estrogen receptor modulator, made headlines in 1998 when the U.S. Food and Drug Administration (FDA) made it the first approved agent for the chemoprevention of breast cancer in women at increased risk. However, tamoxifen can cause rare but serious side effects. Specifically, it has been shown to increase the risk for endometrial and other uterine cancers, blood clots and strokes, and cataracts. Tamoxifen has also been shown to increase menopausal symptoms (e.g., hot flashes) and minor gynecologic problems (e.g., vaginal dryness).

The STAR results show that raloxifene, a second-generation selective estrogen receptor modulator, has fewer risks. Compared with women taking tamoxifen, those taking raloxifene had

• 36% fewer uterine cancers (including endometrial cancer),
• 36% fewer pulmonary embolisms,
• 26% fewer cases of deep-vein thrombosis, and
• 21% fewer cataracts.

“I think that the results are very exciting,” Dr. Bevers said. “A lot of women and their doctors have not elected to pursue tamoxifen as a breast cancer risk reduction agent for a variety of reasons, including the small but real risk of developing serious side effects. Now we are talking about a drug, raloxifene, that they are very familiar with and have been using for many years as an osteoporosis preventive agent. What the STAR data are really providing them with is another benefit of raloxifene use.”

The STAR trial was prompted by findings from an osteoporosis study evaluating postmenopausal women taking raloxifene to prevent osteoporosis. An incidental finding of the study indicated a lower-than-normal incidence of invasive breast cancer in study participants. The STAR data confirm that the benefit is also conferred to postmenopausal women at increased risk for breast cancer, a group numbering about 9 million in the United States, Dr. Bevers noted. Raloxifene’s maker, Eli Lilly & Co., has announced its intention to ask for FDA approval of raloxifene for the chemoprevention of breast cancer in postmenopausal women.

So far, the STAR data do not indicate that raloxifene and tamoxifen conferred different benefits related to race, age, family history, or other breast cancer risk factors; likewise, when breast cancers did occur, the treatment groups did not differ in terms of the size of the primary tumor, lymph node involvement, or estrogen receptor status. Even the costs of tamoxifen and raloxifene are similar, with the former averaging about $100/month and the latter about $75/ month, the STAR researchers noted.

Although the STAR findings are compelling, tamoxifen will not soon be abandoned, Dr. Bevers noted. STAR enrolled only postmenopausal women; tamoxifen, conversely, has been approved for use in both pre- and postmenopausal women. In addition, raloxifene was not as effective as tamoxifen in controlling the incidence of noninvasive breast cancers (lobular carcinoma in situ and ductal carcinoma in situ). This finding is in concordance with previous research, but the reasons for it remain unclear.

The NSABP is eagerly anticipating the next study in the fight against breast cancer to open late fall 2006. Its plan to compare raloxifene and an aromatase inhibitor has already been submitted to the NCI for approval. Aromatase inhibitors have been shown to be more effective than tamoxifen in preventing second breast cancers. Plans for participation are underway at M. D. Anderson. Physicians interested in learning more about referring to or participating in breast cancer prevention clinical trials may contact (713) 792-8064.

For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789.

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