Most women with an elevated risk for breast cancer will not live longer if they take the cancer prevention drug tamoxifen, a new study shows.

Researchers concluded only very high-risk women benefit in terms of life expectancy when they take the drug for prevention.

They calculated that women at the lower end of the high-risk scale would spend a whopping $1.3 million per year of life added if they purchased tamoxifen in the United States. In Canada, where the drug sells for much less, the cost per year of life saved was estimated to be about one-tenth that amount.

The researchers used a computer-generated model to predict life expectancies for a hypothetical group of women at high risk for breast cancer who did and did not take tamoxifen to lower their risk.

Researcher Joy Melnikow, MD, of the University of California-Davis, tells WebMD the model showed tamoxifen had less of an impact on mortality (death) than expected because it does not protect against the most deadly breast cancers -- those not fueled by estrogen.

Tamoxifen is a selective estrogen receptor modulator (SERM) drug that works as an antiestrogen. Estrogen promotes the growth of most breast cancer cells. So the drug targets estrogen receptors on the cancer cells, which blocks estrogen from them. It is widely used as a breast cancer treatment, and was approved in 1998 by the FDA to lower breast cancer risk in women at high risk.

“The fact that the cancers prevented by tamoxifen and (the SERM) raloxifene are easier to treat and have a better prognosis really hasn’t been considered before,” Melnikow says.

All in the Numbers

Tamoxifen was approved for prevention, based on findings from a landmark government study in which high-risk women who took the drug for five years had a 49% reduction in breast cancer incidence, compared with women who did not.

High risk was defined as having at least a 1.67% risk of developing breast cancer within five years, based on a standardized risk assessment tool known as the GAIL model.

In the latest study, however, researchers estimated that mortality rates would actually increase slightly in women with this level of risk when the impact of estrogen-receptor negative breast cancers was considered. Estrogen-receptor negative breast cancers are not fueled by estrogen and therefore not helped with tamoxifen.

Meanwhile, tamoxifen use is associated with an increased risk for uterine cancer. Tamoxifen is also associated with increased risk for serious blood clots that can be life-threatening, and for cataracts.

The researchers concluded it would take a breast cancer risk of greater than 3% to derive a potential mortality benefit from tamoxifen.

The model did show a mortality benefit for tamoxifen users at all levels of risk if the women had had hysterectomies. The increased risk of uterine cancer from using tamoxifen does not exist for these women.

“The projected benefits of tamoxifen for women at or near the threshold risk for breast cancer of 1.67 percent are very small or nonexistent,” Melnikow and colleagues conclude in the Sept. 1 issue of the American Cancer Society journal Cancer.

Melnikow tells WebMD that women with a five-year breast cancer risk of less than 2.5 percent or 3 percent should probably not take tamoxifen, especially if they have not had hysterectomies.

Tamoxifen vs. Raloxifene

Breast cancer prevention researcher D. Lawrence Wickerham, MD, of the National Surgical Adjuvant Breast and Bowel Project (NSABP), tells WebMD that very few women at the low end of the high-risk scale are taking tamoxifen for prevention.

Wickerham and colleagues recently reported findings from a long-awaited study comparing tamoxifen to raloxifene for breast cancer prevention in postmenopausal women.

He tells WebMD that the Study of Tamoxifen and Raloxifene (STAR) showed both drugs worked equally well, reducing breast cancers to about half of what would have been expected. But raloxifene was found to have a better safety profile, with a lower risk of causing uterine cancer, blood clots, and cataracts.

Raloxifene, which is manufactured by Eli Lilly and sold under the brand name Evista, is widely prescribed for osteoporosis, but it has not yet been approved for breast cancer prevention.

Fewer Side Effects?

“We viewed raloxifene as the winner, not because it was more effective, but because it was as effective as tamoxifen with fewer side effects,” Wickerham says. “Raloxifene may prove to be the drug that makes prevention treatment both practical and effective.”

But breast cancer specialist William J. Gradishar, MD, is not yet convinced. In an editorial evaluating the STAR results, Gradishar noted that the difference in side effects between the two drugs was slight and that tamoxifen seemed to prevent more noninvasive breast cancers than raloxifene.

“Although media coverage of the early release of data from the STAR trial suggests a clear winner in raloxifene, the data from clinical end points and patient-reported symptoms suggest a less clear conclusion,” Gradishar wrote.

Reluctance to Use Drug

The Northwestern University oncology professor tells WebMD that women and their primary care physicians have been slow to embrace tamoxifen for cancer prevention. He does not see them flocking to raloxifene once it is approved for this use.

“We are asking women to take a costly drug with potential side effects every day for five years to lower their risk for a cancer than may or may not occur,” he says. “Not many women have been willing to do that.”

And large numbers probably won’t, he says, until better breast cancer prevention drugs with fewer side effects become available or there are better ways of identifying the women who are likely to get breast cancer.

If you’re considering using one of these drugs, talk to your physician about what your breast cancer risk is.

By Salynn Boyles, reviewed by Louise Chang, MD

SOURCES: Melnikow, J., Cancer, Sept. 1, 2006; vol 106: online edition. Joy Meinikow, MD, MPH, Department of Family and Community Medicine, University of California-Davis, Sacramento, Calif. D. Lawrence Wickerham, MD, associate chair of the National Surgical Adjuvant Breast and Bowel Project, National Institutes of Health. William J. Gradishar, MD, Division of Hematology/Oncology, Northwestern University, Feinberg School of Medicine, Chicago.