A new class of medications has emerged as a potentially powerful weapon against breast cancer, cutting by almost half the chance of recurrence in post-menopausal women who have completed a standard course of drug therapy, scientists reported yesterday.
The results were so impressive that scientists directing a five-year study in the United States, Canada and Europe halted the trial midway so that women taking placebos in a comparison group could be offered the active drug, known as letrozole.
Yesterday, the New England Journal of Medicine put a report by the study's investigators online, about a month ahead of the print edition's Nov. 6 publication date (www.nejm.org).
Five years of treatment with a drug called tamoxifen has long been the standard treatment for post-menopausal women whose cancers are stimulated by the female hormone estrogen. They account for the majority of breast cancer patients, and many have had mastectomies or lumpectomies.
But studies show tamoxifen doesn't always help if taken for longer than five years and may even switch its effect and trigger recurrences. So researchers have been looking for drugs to pick up where tamoxifen leaves off.
"For years we have thought we had reached the limit of what we could do to reduce the risk of recurrence with five years of tamoxifen," Dr. Paul E. Goss, the lead investigator from Prince Margaret Hospital in Toronto, said in a statement.
"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."
The new drugs are called aromatase inhibitors, which work by decreasing the body's production of estrogen. Tamoxifen fights estrogen through a different route - by blocking the tumor receptors that estrogen uses to invade cells.
The study, coordinated by the National Cancer Institute of Canada, tested a daily dose of letrozole - an aromatase inhibitor - against a placebo in women who had recently completed five years of tamoxifen. Nearly 5,000 participants were randomly assigned to receive either the drug or placebo.
After an average of 2.4 years, there were 132 cancers in the placebo group compared with 75 in the letrozole group. Because the drug depletes estrogen, side effects included hot flashes and a slightly increased risk of bone fractures.
Dr. Nancy Davidson, director of the breast cancer research program at the Johns Hopkins Kimmel Cancer Center, said positive results were surprising.
"I don't think anyone thought we'd be sitting here today with such positive results over this short period of time," said Davidson, who directed several hundred doctors in the study and enrolled patients of her own. "We thought any benefit we might observe would take several more years to become evident."
She said the study could have broad implications, offering a possible course of treatment to a group of women that numbers 90,000 in the United States alone.
With the study halted early, however, doctors will not learn answers to some important questions, such as the optimal length of treatment and the potential side effects of continued therapy. Also open to question is whether the drug helps or harms patients when taken over a longer period of time.
Other trials now in progress will answer some but not all of these questions, scientists said.
"Because of the early termination of the trial, one can say only that letrozole treatment for a period of two to three years has been evaluated and that the optimal duration of such therapy has not been established," Dr. Harold J. Burstein, an oncologist with Harvard's Dana-Farber Cancer Institute, wrote in an editorial.
In the meantime, he wrote, a woman considering letrozole should be "carefully educated about the realistic benefits and the likely side effects of therapy so that she can make a well-informed decision."