WASHINGTON — Medical researchers will begin the first large-scale breast cancer prevention study for high-risk women using the most widely prescribed cancer drug in the world, the National Cancer Institute announced Wednesday.
The trial, expected to involve 16,000 women ages 35 and older and to last from five to eight years, will try to determine whether the drug tamoxifen can reduce the incidence of breast cancer in women at greatest risk of developing the disease. It also will look at whether the drug can decrease the chances of coronary heart disease and osteoporosis.
Breast cancer and heart disease are among the leading killers of American women. Breast cancer, which will afflict one in every nine women, will be diagnosed in an estimated 180,000 women in the United States this year and cause 46,000 deaths. Osteoporosis, a degenerative bone disease, afflicts an estimated 24 million American women, resulting in about 1.3 million fractures annually.
"These are diseases that take a terrible toll in our nation," said Dr. Samuel Broder, director of the cancer institute. "We have made breast cancer an urgent priority, and we need to develop effective preventive strategies. We need answers to these important questions."
The study is unusual--and possibly controversial--because it involves giving a drug with some risks and side effects to women who have not yet developed a disease. It also signals a growing feeling among cancer scientists that research should begin to place more emphasis on prevention than on treatment.
"This study is an extremely important advance in focusing our attention on prevention, instead of waiting for cancer to strike--but not only cancer," Broder said. "We certainly expect that this is not the last prevention study we're going to do."
The study also is part of a new thrust by the National Institutes of Health, the parent agency of the cancer institute, to earmark more research dollars and attention to women's health issues. NIH Director Bernadine P. Healy last year announced that the agency would begin a multi-year research project aimed at learning more about the health problems of older women.
The $68-million breast cancer study will involve 270 sites across the United States and Canada. The 16,000 women will be divided randomly into two groups, one of which will be given 20 milligram doses of tamoxifen daily. The other group will take a placebo, a pill with no medical value. Neither the women nor the physicians will know who is taking which pill, a process known as "double-blinding." It allows researchers to see the possible benefits and side effects of the drug without being influenced by other factors.
The study is part of the National Surgical Adjuvant Breast and Bowel project, a large group of cancer researchers funded by the cancer institute. The project is headed by Dr. Bernard Fisher, a professor of surgery at the University of Pittsburgh in Pennsylvania who also will be the principal investigator on the breast cancer prevention study.
A woman at high risk of developing breast cancer has only two options: preventive mastectomy before she is diagnosed or "watchful waiting," Broder said, adding: "We want to know if tamoxifen can change that equation."
Risk is determined by many factors that will be considered in choosing participants in the study. Women over 60, for example, are at least five times more likely to develop breast cancer than women between 35 and 39.
Women who have been diagnosed with lobular carcinoma \o7 in situ\f7 , a non-invasive, or localized, breast cancer, are nine times more likely than the average woman to develop invasive breast cancer. In fact, the condition is considered a marker for the more serious and aggressive form of breast cancer.
Also at higher than normal risk are women whose mothers, sisters or daughters have had the disease; women whose menstrual periods began early, usually before age 12, and women who have never had children or were over 30 when their first child was born.
Researchers believe that tamoxifen could reduce breast cancer and heart disease by as much as 40% and osteoporosis by 30% to 33%.
The drug has been used for nearly 20 years to treat patients with advanced breast cancer; since 1985 it has been used as an adjuvant, or additional, therapy after radiation and/or surgery for early breast cancer.
The drug works by interfering with the activity of estrogen, a female hormone that promotes the growth of cancer cells in the breast.
As a treatment, it slows or stops the growth of cancer cells. As adjuvant therapy, tamoxifen helps prevent the original breast cancer from returning. Research also has shown that as an adjuvant therapy, it may prevent the development of new cancers in the opposite breast.
For that reason, researchers believe tamoxifen may have prevention abilities in healthy women.