An updated analysis from an international clinical trial of the drug letrozole was presented on June 8, 2004 at the American Society of Clinical Oncology annual meeting in New Orleans. With additional follow up now available to a median of 2.5 years, letrozole (Femara) was found to be effective in reducing local and distant recurrences of cancer, as well as new breast cancers, regardless of whether the patient's cancer had spread (node-positive) or had not spread (node-negative) to the lymph nodes at the time of diagnosis. The rate of distant breast cancer spread was reduced by 40 percent compared to placebo. Most importantly, with the additional followup available for this new analysis, letrozole now shows an improvement of 39 percent in overall survival for node-positive patients.
"Of equal interest to the good news on survival, additional follow up did not show any further increase in side effects related to bone fractures or heart," said Jeffrey Abrams, M.D., coordinator of the U.S. National Cancer Institute's Cooperative Group breast cancer treatment trials. "While a survival advantage has not yet appeared for patients with node-negative disease, their results do parallel those seen in node-positive tumors."
Follow up with women in this study will continue for another ten to fifteen years. Other studies are being planned or are in progress to examine the issue of when is the optimal time to switch women on tamoxifen to aromatase inhibitors, such as letrozole, and for how long these drugs could be administered.
Original Statement:
A Canadian-led international clinical trial has found that post-menopausal survivors of early-stage breast cancer who took the drug letrozole after completing an initial five years of tamoxifen therapy had a significantly reduced risk of cancer recurrence compared to women taking a placebo. The results of the study appear in today's advance on-line edition of the New England Journal of Medicine.
The clinical trial has been halted early because of the positive results and researchers are notifying the 5,187 women worldwide who have participated in the study. Women on letrozole will continue taking the drug and those on the placebo can begin taking letrozole, if they wish.
"This very important advance in breast cancer treatment will improve the outlook for many thousands of women," said Andrew von Eschenbach, M.D., director of the National Cancer Institute which led the study in the United States. "This is one more example of the ability to interrupt the progression of a cancer using a drug that blocks a crucial metabolic pathway in the tumor cell."
Study researchers found that letrozole, when taken after five years of tamoxifen therapy, substantially increased the chance of remaining cancer free. In total, 132 women taking the placebo had their disease recur compared to 75 on letrozole. Overall, letrozole reduced the risk of recurrence by 43 percent, so that after four years of participating in the trial, 13 percent of the women on the placebo, but only seven percent, of those on letrozole had recurred. Deaths from breast cancer were also reduced. Seventeen women taking the placebo died of breast cancer compared to nine taking letrozole.
While tamoxifen is widely used to prevent breast cancer recurrence in post-menopausal women, it stops being effective after five years because, researchers believe, tumours become resistant to it.
"More than half of women who develop recurrent breast cancer do so more than five years after their original diagnosis," says Paul Goss, M.D., of Princess Margaret Hospital in Toronto. "For years, we have thought that we had reached the limit of what we could do to reduce the risk of recurrence with five years of tamoxifen. Our study ushers in a new era of hope by cutting these ongoing recurrences and deaths from breast cancer after tamoxifen by almost one half." Goss, a leading expert in novel hormone therapies for the treatment and prevention of breast cancer, conceived and chaired the international trial with letrozole.
A form of hormone therapy for the treatment of breast cancer, letrozole works by limiting the ability of an enzyme called aromatase to produce estrogen, a major growth stimulant in many breast cancers.
Mayo Clinic medical oncologist James Ingle, M.D., says, "Based on our findings, all post-menopausal women with hormone-receptor positive tumours completing about five years of tamoxifen should discuss taking letrozole with their doctors to reduce their risk of breast cancer recurrence." Ingle, from Rochester, Minn., led the research study in the United States.