TUESDAY, Nov. 15, 2005 (HealthDay News) -- The final results of a 13-year study confirm that tamoxifen, a drug long used to treat breast cancer, can also prevent the malignancy in healthy women at high risk for the disease.
"This study proves the principle that prevention is a legitimate kind of approach to treating breast cancer, and justifies the continuing research to find [preventive] drugs with less side effects and better risk reduction," said lead researcher Bernard Fisher, a founding member and director of the National Surgical Adjuvant Breast and Bowel Project (NSABP).
The findings appear in the Nov. 16 issue of the Journal of the National Cancer Institute.
Tamoxifen is one of a class of drugs called selective estrogen receptor modulators (SERMs). These drugs work by attaching to the molecule in breast cancer cells that normally reacts with estrogen, stopping the cells' growth and limiting cancer spread, according to the American Cancer Society.
The NSABP study began in 1992 and tracked the health outcomes of more than 13,000 healthy women at high risk for breast cancer. Participants took either 20 milligrams of tamoxifen or a placebo every day for five years.
Researchers wanted to learn if the drug, so effective in preventing breast cancer recurrence, could also be used to prevent the disease from developing in high-risk women. The study was double-blinded, meaning that neither the study participants nor their doctors knew who was getting the medication.
After six years, researchers found the rate of incidence of invasive breast cancer was nearly 50 percent lower among women who took tamoxifen -- a result so dramatic that researchers lifted the double-blind aspect of the study to allow those women on placebo to take tamoxifen. Approximately one-third of that group opted to take the drug.
Now, after following the majority of the women for another seven years, the researchers found the rates of invasive breast cancer continued to be much lower for women who took tamoxifen. The cumulative rate of invasive breast cancer over the course of the study was reduced from 42.5 per 1000 women in the placebo group to 24.8 per 1000 women in the tamoxifen group -- a 43 percent reduction.
Also significantly lower were the incidence rates for noninvasive cancers, such as ductal breast cancer in situ (DCIS), which fell by 37 percent among women who took tamoxifen vs. placebo.
"This is the only proven prevention method for breast cancer," Fishman said. The study was supported by grants from the U.S. National Cancer Institute and the U.S. Department of Health and Human Services.
The beauty of this study, said Claudine Isaacs, director of the Clinical Breast Cancer Program at Georgetown University's Lombardi Comprehensive Cancer Center, is that it was placebo-controlled, had a very large group of participants and focused on prevention.
"Because it is focused on prevention, they did a very careful assessment of the side-effect profile," she said.
Tamoxifen's side effects were both beneficial and potentially harmful, and included a 32 percent decrease in bone fractures over seven years of follow-up and an increase in risks for uterine cancer, stroke, pulmonary embolism and cataracts.
Isaacs said doctors can use a well-validated risk/benefit model that includes a woman's age, medical and family histories and other factors to help her decide whether tamoxifen might be right for her.
"A clinician should go through the risk/benefit ratio with a patient, and if the benefits outweigh the risks, he can tell her she should consider [tamoxifen]," she said, adding that it is very much a personal choice.
The researchers estimate that of all American women between 35 and 70 years of age, about 25 percent -- 2.5 million -- are at high risk for breast cancer and could be helped by using tamoxifen.
However, despite the positive NSABP findings, a study published earlier this year found that many women at high risk for breast cancer were reluctant to take tamoxifen to help prevent the disease.
Researchers at the University of California at Davis told 255 women that they were eligible for preventive tamoxifen therapy if their estimated risk for breast cancer was 1.66 or above. The estimated average five-year risk among the 255 women in the study was 2.8.
But even after an educational session explaining tamoxifen's potential risks and benefits, only 45 of the women -- just 17.6 percent -- said they would be inclined to take the drug on a regular basis to help prevent breast tumors.
Study author Dr. Joy Melnikow, a professor of family and community medicine at the UC Davis, said it seemed that the women in the study had seen friends get breast cancer and survive, and weren't as afraid of the disease as one would think.
"They didn't see it as a death sentence," she told HealthDay.
In other recent research on tamoxifen, Swedish researchers found that breast cancer survivors who took tamoxifen for five rather than two years not only reduced their risk of death from all causes, including heart disease, but were at a decreased risk of developing cancer in the other breast.
Trials are currently underway involving drugs that might carry fewer side effects than tamoxifen and further reduce breast cancer risk, Fishman said. Raloxifene, a drug originally developed to treat osteoporosis, is just one of these candidate drugs, he noted.
And in another study, doctors at the Virginia Commonwealth University Massey Cancer Center in Richmond, Va., combined two novel drugs called UCN-01 and a MEK 1/2 inhibitor to treat breast cancer in mice. When used together, the drugs -- which have a low toxicity to healthy cells -- killed 75 percent of the cancer cells in the animals and suppressed tumor recurrence. The findings were published in the Nov. 14 online issue of Cancer Biology and Therapy.
More information
For more on breast cancer, head to the National Cancer Institute.
