TORONTO, Oct. 9 (UPI) -- An important new study suggests women can slash their risk in half of suffering a return bout of breast cancer if they take the drug letrozole after completing five years of therapy with tamoxifen, the current standard therapy.
"This is good news for women," said Dr. Barbara Whylie, director of cancer control policy at the Canadian Cancer Society in Toronto. "The results of this new study can give breast cancer survivors a better hope for life without cancer."
At a news briefing that coincided with publication of the research in the on-line version of the New England Journal of Medicine, doctors reported post-menopausal women treated with letrozole after completing five years of tamoxifen resulted in a 43-percent reduction in breast cancer recurrence, compared to women using a placebo after tamoxifen.
Originally scheduled for five years, the trial was terminated early -- after about two years -- when an interim analysis showed patients treated with letrozole were doing far better than those on the placebo.
Dr. Paul Goss, the lead investigator, from Toronto's Princess Margaret Hospital, said this finding could lift "a dark cloud (that) hangs over patients" after surgery to remove breast cancer and five years of tamoxifen treatment. "There has been no standard-of-care treatment following that period," he said.
Now, however, Goss continued, "there is no question that these results show that taking letrozole after tamoxifen reduces recurrence of breast cancer." He added the treatment regimen results in reduced recurrence in the same breast, in the opposite breast and in spread of cancer to other parts of the body.
The trial enrolled 5,187 women -- from Canada, the United States and Europe at more than 200 sites -- who received either placebo or letrozole. The drug is known as an aromatase inhibitor. It is designed to prevent the manufacture of estrogen in the body. In about 50 percent of women, breast cancer tumor growth can be enhanced by estrogen.
In addition to letrozole, which is manufactured by Novartis of East Hanover, N.J., and sold under the trade name Femara, other aromatase inhibitors currently available include anastrozole, made by AstraZeneca of Waltham, Mass., and sold as Arimidex, and exemestane by Pharmacia of Peapack, N.J., sold as Aromasin.
In the trial, Goss and colleagues found 207 breast cancers recurred in women after an average of 2.4 years. Of those cancers, 75 occurred in the letrozole group and 132 in the placebo group. The estimated four-year, disease-free survival rates were 93 percent for the letrozole patients and 87 percent for the placebo patients.
"These findings will be of intense interest to hundreds of thousands of women," said Dr. James Ingle, a medical oncologist at the Mayo Clinic in Rochester, Minn., who led the U.S. component of the study. "The results indicate that we have something following those first five years after tamoxifen. We are seeing a 43 percent reduction in risk without additional side effects. We can have confidence in these results."
That confidence was not mirrored, however, in an accompanying editorial in the New England journal, by Dr. Harold Burstein of Dana-Farber Cancer Institute, the department of medicine at Brigham and Women's Hospital and Harvard Medical School in Boston.
"A woman who is considering letrozole therapy after five years of tamoxifen therapy in order to reduce further the risk of a recurrence of breast cancer should be carefully educated about the realistic benefits and the likely side effects of therapy so that she can make a well-informed decision," Burstein wrote. He added previous studies have shown aromatase inhibitors are associated with osteoporosis and related bone fractures, hot flashes and night sweats, arthritis and sexual dysfunction. "Although letrozole therapy was generally well tolerated and convenient (in the trials), individual patients may have more pronounced symptoms and be forced to weigh carefully the benefits and side effects of treatment. The long-term safety of aromatase inhibitors is uncertain, and the supplemental data on bone density, cardiovascular health, and quality of life collected as part of this trial have yet to be reported."
Dr. Diane Young, vice president for clinical development at Novartis, said the company is planning to seek Food and Drug Administration approval to use letrozole following tamoxifen based on the results. "We expect to file ... by the second half of 2004," she told United Press International.
Young said her company expected the results to be positive, but she said she was surprised at how soon the differences between letrozole and placebo were seen and how deep the differences between the treatments became.
Novartis contributed about $12 million ($20 million Canadian) to the study, which was conducted in conjunction with the Canadian Cancer Society, the National Cancer Institute of Canada and the National Cancer Institute of the United States, she said.
Goss said he developed the study design along with other researchers and then approached Novartis for the funding.
Because the study was stopped early, Ingle said it left numerous questions unanswered, however, including the optimal time a person should take letrozole after the tamoxifen regimen.
Goss noted cancer cells find a way to become resistant to tamoxifen after five years and said he suspects a similar resistance to letrozole could arise as well.
Young said other trials now are under way with letrozole to study various uses of the drug. One trial compares letrozole directly to tamoxifen. The same trial also looks at whether there are advantages to treating patients first with letrozole and then tamoxifen.
Ingle noted the trial results announced Thursday only apply to post-menopausal women with hormone-dependent cancers. Of the 211,000 new cases of breast cancer currently diagnosed in the United States each year, Ingle said about 84,000 would be expected to be hormone-dependent.