Tamoxifen may be the best cancer prevention drug that no one wants to take.

Seven years ago, researchers announced that a federally-sponsored study involving more than 13,000 healthy women at high risk for breast cancer showed that tamoxifen could cut the risk of invasive breast cancer in half.

The Breast Cancer Prevention Trial thus became a landmark study, demonstrating for the first time that a drug could reduce the risk of a first cancer, not just the risk of a recurrence. And a final report, being published today in the Journal of the National Cancer Institute, boasts similar results after seven years of follow-up.

But tamoxifen, which is widely used and highly effective in preventing recurrence of breast cancers, never caught on as a preventive drug.

"I think women understand that what we're talking about here is a reduction in risk, we're not really talking about [absolutely] preventing a disease," said Fran Visco, a breast cancer survivor and president of the National Breast Cancer Coalition.

Side effects, including an increased risk of uterine cancers, blood clots and cataracts, thus weigh heavily for healthy women, even if they are at increased risk for breast cancer.

And, she said, too many other questions remain, such as: How long should a woman take tamoxifen? Will it reduce breast cancer deaths, or just reduce or delay the onset of breast cancer? What are the long-term risks and benefits?

Dr. Bernard Fisher, the principal investigator since the trial began in 1992, said it is a shame that more women don't take advantage of the drug, contending the benefits outweigh the drug's risks for women at high risk of breast cancer.

The net benefit is of considerable magnitude for women younger than 49, he emphasized. Women in that age group are less susceptible to tamoxifen's side effects. The risks of side effects increase with a woman's age and African-American women seem particularly vulnerable, according to the new report.

The original study found that tamoxifen reduced the risk of invasive cancers -- those that have spread into surrounding healthy tissues -- by 49 percent; the new report notes a risk reduction of 42 percent after seven years. Likewise, the original study found a 45 percent reduction in risk of non-invasive breast cancers, compared with 35 percent after the longer follow-up.

The new numbers are similar to the original findings, Dr. Fisher said, even though women had stopped taking tamoxifen for the last two years of the follow-up.

"This confirms the original findings," he said. "They still hold up."

The study, run by the Pittsburgh-based National Surgical Adjuvant Breast and Bowel Project, looked at the effect of tamoxifen on healthy women considered at high risk for breast cancer. Risk increases with age, so all women older than 60 qualified for the study. Younger women whose risk was equivalent to that of a 60-year-old women also were included.

But in 2001, researchers at Memorial Sloan-Kettering Cancer Center in New York City found that of 43 at-risk women, only two elected to take tamoxifen as a preventive measure. Fear of side effects was the most common reason they cited for refusing the drug and educational sessions had no effect on their decisions.

Results by Canadian researchers, published this past summer in the Annals of Family Medicine, were even more dismal. Of 89 high-risk women identified at a breast referral center, only one opted to take tamoxifen. All were advised to discuss the issue with their family physicians, but only 48 did so. In eight cases, the physicians made no recommendations and in 37 cases the physicians recommended against taking the drug.

Dr. Fisher and Dr. Leslie Ford, associate director of the National Cancer Institute's cancer prevention division and a co-author of today's report, emphasized that the Breast Cancer Prevention Trial was important in establishing that it was possible to use a drug to prevent a primary cancer. It thus set the stage for ongoing clinical studies of other drugs, including raloxifene, anastrozole and exemestane, which may have fewer side effects than tamoxifen.

"Unless you hit a home run, you can always do better," said Dr. Fisher, noting that researchers hope the new drugs will show advantages over tamoxifen. "But until the other studies have produced results that show a better net benefit, then tamoxifen is still the drug of choice."

It would be nice if those new drugs are a clear improvement over tamoxifen, Ms. Visco said, but they, too, likely will have side effects. As experience has shown since the Breast Cancer Prevention Trial concluded, healthy women have a much lower threshold for risk than do women who are being treated for disease, she added.

"Without question, these trials are helping us learn more about benefit and risk," she said. Women are learning more about these issues and discussing them with their doctors. "I think that's a very good thing."