Study shows raloxifene may be acceptable for women coming off tamoxifen, say researchers

DT Capsules

• Raloxifene, used to treat osteoporosis, may be just as effective in fighting breast cancer as tamoxifen.
  
• Women assigned to take raloxifene daily had 36% fewer uterine cancers and 29% fewer blood clots than the women who were assigned to take tamoxifen.
  
• Test results may be encouraging to women with osteoporosis, but they reflect only women who have never had breast cancer.

Dora Townsend's oncologist recently took the 58-year-old Pennsylvania woman off tamoxifen, which she'd been taking as the result of having had breast cancer—for the second time—11 years ago. Her doctor told her that the possible benefits of tamoxifen diminish after about five years. Therefore, said the oncologist, tamoxifen's demonstrated, if small, risk of uterine cancer and blood clots was a good reason to quit the drug.

But Townsend also has osteoporosis, and she wanted to take raloxifene (Evista, Lilly) for that condition. When she asked her rheumatologist about raloxifene, she was told that that drug is chemically very similar to tamoxifen, "and if I couldn't take tamoxifen, I shouldn't take raloxifene. The net result of all this was a great deal of confusion. I was—and am still—uncertain as to what to do."

Her situation is not uncommon. Many women who have been warned off tamoxifen have also been warned away from raloxifene because the two drugs are so molecularly similar, said Steven Applebaum, M.D., an oncologist at Huntington Hospital in Pasadena, Calif. He was a leading researcher in the Study of Tamoxifen and Raloxifene, or STAR—one of the largest breast cancer prevention clinical trials ever conducted.

The study's preliminary results were announced last month and have led to some controversy. Officials of several professional and advocacy organizations have expressed concern that news reports have overstated the value of the study's preliminary findings.

Researchers said they found that raloxifene works as well as tamoxifen in reducing breast cancer risk for postmenopausal women at increased risk of the disease: Both drugs reduced the risk of developing invasive breast cancer by about 50%.

The preliminary results may offer some particular encouragement to Townsend and others who are considering taking raloxifene for osteoporosis, but have stopped taking tamoxifen, said Applebaum. The STAR researchers found that women on raloxifene had 36% fewer uterine cancers and 29% fewer blood clots than women taking tamoxifen. "That would imply that the demonstrated risks of raloxifene are less than the risks of tamoxifen," he said. "The implication is that the use of raloxifene does not add additional risk. That is only an implication, not a finding, for women who have already had breast cancer. But it is also worth noting that raloxifene's benefit in treating osteoporosis is very well established."

Applebaum also said, however, that "it is extremely important to note that this initial study reflects only women who never had cancer. No data exist yet on raloxifene and women who have had breast cancer. We don't know whether raloxifene is effective in these women. And we don't have information on associated risks for those women. That research is being conducted."

Among cancer doctors expressing concern about the STAR results is Laura Esserman, M.D., director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco Medical Center. She was quoted recently as saying that rather than being a breakthrough, the results have not been peer reviewed and that tamoxifen should remain the drug of choice for treating postmenopausal women at risk for breast cancer. She is joined in her skepticism by leaders of several advocacy groups, including the National Women's Health Network and San Francisco-based Breast Cancer Action.

Officials of the American Cancer Society also are publicly expressing concern that the STAR results may have been overblown. They point to the fact that, notwithstanding percentages, the comparative numbers of actual incidences of uterine cancer and blood clots are so low that women should be cautious about assuming raloxifene is safer than tamoxifen. They consider statements like the following to be hyperbole:

"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," said Leslie Ford, M.D., associate director for clinical research at the National Cancer Institute's Division of Cancer Prevention, in a public statement. "For many women, raloxifene's benefits will outweigh its risks in a way that tamoxifen's benefits do not."

Applebaum said more research is needed, but that the initial STAR results are meaningful: "This study answers only one question: What are the effectiveness and risks of taking raloxifene for postmenopausal women who have never had breast cancer? More work most certainly has to be done," he said.
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STAR study examined side effects for nearly 20,000 women

The Study of Tamoxifen and Raloxifene (STAR) was coordinated by the National Surgical Adjuvant Breast and Bowel Project, a network of cancer research professionals, and was sponsored by the National Cancer Institute. STAR enrolled 19,747 postmenopausal women who were at increased risk of the disease.

Participants were randomly assigned to receive either 60 mg of raloxifene (Evista, Lilly) or 20 mg of tamoxifen daily for five years. Women 60 to 64 years old have a 1.66% chance of getting breast cancer within five years. The STAR participants had more than twice that risk, around 4%.

Of the women taking tamoxifen in the study, 36 of 4,732 got uterine cancer. Of the women taking raloxifene, the number was 23 out of 4,712. Women who had had hysterectomies were not counted. Of the 9,726 women on tamoxifen, 141 developed blood clots. Of the 9,745 women on raloxifene, 100 got blood clots.

STAR is the second recent study to demonstrate that raloxifene can be effective in reducing incidence rates of first-occurrence breast cancer. In 2004, a four-year study titled Continuing Outcomes Relevant to Evista (CORE), involving more than 3,500 postmenopausal women with osteoporosis, found that the use of the drug resulted in a 59% lower risk of invasive breast cancer and a 66% lower risk of developing estrogen-receptor positive breast cancer, compared with women who had taken a placebo. CORE was part of a study titled the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, which sought to assess raloxifene's effectiveness in treating osteoporosis and, as a secondary measure, how effective it was in reducing breast cancer risk.

THE AUTHOR is writer based in Gettysburg. Pa.