Hailing it as a new hope for hundreds of thousands of older breast cancer patients, investigators in a large Canadian-led international trial have shown that a drug given after standard treatment with tamoxifen can cut the risk of the cancer recurring nearly in half.

The study was halted earlier than planned after researchers found that participants who took the drug letrozole had a 43 percent reduction in breast cancer recurrence compared with those taking a placebo. The reseachers also found that the letrozole group had 46 percent fewer new cancers in the previously healthy breast.

"Our study stopped early because we did not want to imperil the lives of women taking placebo any further," explained trial leader Dr. Paul Goss of Toronto's Princess Margaret Hospital. They will have the option to begin treatment with letrozole, which is marketed as Femara.

"The results of this important study offer new hope to hundreds of thousands of breast cancer patients and their families," Goss said. The findings were announced yesterday at a press conference in Toronto and were published in the early online edition of the New England Journal of Medicine.

Ending what was to be a five-year trial when the participants had taken the drug for an average of only 2.4 years means that some medical questions have not been answered. Without more data, it is not clear how long breast cancer patients should take letrozole to get the most benefit with the fewest side effects.

In light of the findings, investigators with the Pittsburgh-based National Surgical Adjuvant Breast and Bowel Project and other centers will be reviewing their own studies of similar drugs.

The study was conducted at sites in Canada, the United States and Europe. The 5,187 participants had been treated for early stage breast cancers, were postmenopausal and, within three months of entering the study, had finished a standard, five-year course of tamoxifen to prevent the cancer from recurring.

The NSABP, which did not participate in the new trial, previously conducted a study showing that more than five years of tamoxifen therapy could do more harm than good and, until now, no other drugs have been shown to reduce the risk of recurrence.

"There's a lifetime risk of recurrence," said Dr. Lawrence Wickerham, associate chairman of the NSABP and an oncologist at Allegheny General Hospital. "It's not overwhelming in magnitude but it's real, and it's why we continue to follow [patients] on a regular basis for life."

Letrozole belongs to a class of drugs called aromatase inhibitors, which block estrogen production. Estrogen, a hormone made primarily by the ovaries in menstruating women, is generated in small amounts after menopause by fat, skin, muscle and other body tissues. About two-thirds of patients have breast cancers that are fueled by estrogen, so researchers predicted that reducing hormone levels would inhibit cancer growth.

All the study participants had hormone-sensitive tumors. They were randomly assigned to take either a daily dose of letrozole or a placebo. The trial was sponsored by Novartis Pharmaceuticals, which is the maker of Femara, the Canadian Cancer Society and the U.S. National Cancer Institute.

In the first review of early data, there were 75 cases of recurrent or new breast cancers in the letrozole group and 132 in the placebo group. Nine women in the letrozole group and 17 in the placebo group died of breast cancer.

That suggests a recurrence can be avoided in one woman for every 16 women treated for four years, Goss said.

Side effects of hot flashes, arthritis and muscle aches were more common in the letrozole group and vaginal bleeding was more common in the placebo group. The researchers said that the drug was generally well-tolerated, but said they saw a slight increase in new cases of osteoporosis that requires further study.

Despite the demonstration of the drug's effectiveness, the early end to the trial has left important questions unanswered.

"What's the magnitude of benefit, what's the proper duration of this particular treatment and what are the long-term side effects and toxicities?" Wickerham said. "We'll sort that out with additional effort."

Dr. James Ingle, a Mayo Clinic oncologist who led the American arm of the trial, said that patients could begin taking letrozole now and more information about long-term use should become available in the next few years.

Ingle estimated that about 94,000 American breast cancer patients annually might be candidates for letrozole. Factors such as the initial severity of the disease must be taken into account before treatment is started.

The doctors advised patients not to rush to their doctors for letrozole prescriptions.

Ingle is part of a similarly designed NSABP trial to test an aromatase inhibitor called exemestane against a placebo.

"What I plan to do is talk to my group of investigators and I will recommend that we close it," he said. "And it's simply because I would have a hard time randomizing patients when I know letrozole is of value."

In another New England Journal article, the NSABP's John Bryant and Chairman Dr. Norman Wolmark wrote that "this [exemestane] trial is in peril as a consequence of the release of data on letrozole."

Wickerham said the exemestane trial has recruited 1,500 patients since its inception two years ago.

Letrozole, exemestane and a third aromatase inhibitor called anastrozole are already approved treatments for cancer that has spread beyond the breast. About 10 clinical trials of these drugs are under way worldwide, Ingle said. Like tamoxifen, they will also be studied as a means to prevent breast cancer in high risk women.