About 16,000 women across North America who are at high risk for breast cancer will participate in the largest
cancer-prevention trial in American history -- a study to determine if the drug tamoxifen can protect women from the deadly disease.
Results of the trials, which will include approximately 100 women in Maryland, will not be known for about eight years.
All told, 270 medical centers in the United States and Canada will participate along with the National Cancer Institute in Bethesda, which is directing the trial.
"Up until now, our best weapon to fight breast cancer has been early detection," said Dr. George Elias, director of surgical oncology at the University of Maryland Medical Center, which will coordinate the study in a network of hospitals across the state.
"But if we could prevent breast cancer from occurring in the first place in some patients, we could truly make a significant impact," he said.
Breast cancer strikes about one in nine women. Over the next 10 years, about 1.5 million women in the United States will be diagnosed with breast cancer and almost a half-million will die of the disease.
The American Cancer Society predicts that about 900 cases of breast cancer will be diagnosed this year in Maryland alone.
Tamoxifen is a synthetic drug that is frequently given to women who have already been diagnosed with cancer and treated surgically or with chemotherapy or radiation. It is used to prevent the recurrence of cancer in a breast, or its spread to another breast.
Tamoxifen has been in use since 1973 in the United Kingdom and since 1978 in the United States, and is now the most frequently prescribed anti-cancer drug in the world.
In one trial, the drug cut in half the frequency of breast cancer spreading from one breast to another in women who had started the drugafter having surgery.
"We have to be very careful in interpreting that data," said Dr. Elias, explaining that such results don't mean the drug can necessarily prevent the disease.
Medical centers will be looking for women between the ages of 35 and 59 who have family histories of breast cancer or previous biopsies of benign tumors -- factors that place them at high risk.
Also, women 60 years or older will be recruited regardless of family or health histories; this is because the disease is far more common among older women. In Maryland, participating hospitals include: the University of Maryland Medical Center, Johns Hopkins Hospital, Mercy Medical Center, Greater Baltimore Medical Center, Harbor Hospital Center and Maryland General Hospital.
The University of Maryland will also recruit women at the Waxter Center for Senior Citizens.
Women will be screened rigorously to ensure they are willing to visit their doctors for annual mammograms and gynecological examinations, and show up every six months for physical exams.
They will also be warned of possible side effects, which include hot flashes and vaginal discharges, according to Dr. Elias.
The drug may also hasten the onset of menopause in women who are already nearing that stage, he said. And younger women will be advised to use birth control because it is not known if the drug can harm a developing fetus.
The drug is also thought to subject women to a slightly increased risk of uterine cancer and blood clots.
Noting the risks, the National Women's Health Network criticized the prevention study, saying tamoxifen is an excellent drug for treating breast cancer but is too dangerous for healthy women.
Once admitted to the study, the women will be randomly assigned to two groups. One will take two tamoxifen pills for at least five years. The other will take placebos.
Neither the volunteers nor their doctors will learn who is getting -- the drug or the placebo until the trial is complete.
Tamoxifen is produced by ICA Pharmaceuticals, a British company with U.S. headquarters in Wilmington, Del.
When it prevents recurrences, it does so by keeping estrogen, a female hormone, from binding to cancer cells. This is effective because estrogen triggers cell division -- the process by which cancer cells multiply out of control.
Physicians hope the drug will prevent tumors in a similar fashion. It would be present in the bloodstream, ready to bind to a single cancer cell before it could divide and spawn the many thousands of cells that constitute a tumor.
"The breast cancers that are diagnosed today did not begin to develop yesterday," said Dr. Bernard Fisher, a University of Pittsburgh surgeon who is the study's principal investigator.
"A number of women who have what appear to be normal breasts without detectable cancers already have the biological
changes that will cause the disease," he said.
WHERE TO CALL
In Maryland, women interested in participating in the study can call (410) 328-5224 or (800) 492-5538.