By Michael Miller
In 2006, an estimated 213,000 women will have been diagnosed with invasive breast cancer, and nearly 41,000 women will die from the disease. Although breast cancer can strike any woman, it is older women, African Americans, the poor and those with limited health care access who are disproportionately affected.
Over the past three decades, intensive research by NIH's National Cancer Institute (NCI) has been applied to all aspects of breast cancer and led to many important discoveries:
- how a healthy breast cell becomes cancerous
- how breast cancer spreads
- why some tumors are more aggressive than others
- why some women suffer more severely and are more likely to die of their disease
Many of the lessons learned have been applied to understanding ways to prevent the disease before it even starts. One of the best ways to prove that a drug or therapy can prevent a disease is to conduct a large, randomized trial. Often these trials require the enrollment of thousands of women to make certain that the results are valid and can be applied to most women.
Since the 1980s, the NCI, in conjunction with the National Surgical Adjuvant Breast and Bowel Project (NSABP), has undertaken two large-scale trials for the prevention of breast cancer.
First was the Breast Cancer Prevention Trial (BCPT), which included more than 13,000 women at increased risk for breast cancer. The BCPT demonstrated the value of the drug tamoxifen in reducing the number of new cases of the disease. The final study analysis was released in November 2005.
"The BCPT should be viewed not only as the first study that demonstrated that breast cancer can be prevented, but also as the beginning from which a new paradigm for breast cancer prevention evolved," says Bernard Fisher, M.D., principal investigator for the trial. "Groups of women at increased risk for breast cancer, who could derive a net benefit from receiving tamoxifen, have been clearly defined."
The study also showed proof of a benefit from tamoxifen beyond the time a woman is taking the pills, notes Leslie Ford, M.D., associate director for NCI's Division of Cancer Prevention and co-author of the study.
Based on the success of the BCPT and results of reports in the medical literature, the Study of Tamoxifen and Raloxifene (STAR) trial was started in 1998. That study enrolled more than 19,000 women to compare the effects of these two drugs in reducing the incidence of breast cancer, and found a reduction in risk of developing breast cancer for both drugs similar to the reduction found for Tamoxifen alone in the BCPT.
Studies, such as BCPT and STAR, involve women who have not had breast cancer, but are at high risk of developing the disease. Most breast cancer prevention research, thus far, has been based on evidence linking the development of this disease, in many cases, with exposure to the hormone estrogen. The focus of recent breast cancer prevention studies has been on testing the effectiveness of drugs called selective estrogen receptor modulators (SERMs). SERMs are drugs that have some antiestrogen properties and some estrogenlike properties. Their anti-estrogen activity may help reduce the risk of breast cancer by blocking the effects of estrogen on breast tissue.
Approximately 5 to 10 percent of women who develop breast cancer have a hereditary form of the disease. Alterations in certain genes make some women more susceptible to developing breast and other types of cancer. Inherited alterations in the genes called BRCA-1 and BRCA-2 (short for breast cancer 1 and 2) are involved in many cases of hereditary breast and ovarian cancer. Testing is available that will determine if there are changes in the BRCA-1 or BRCA-2 genes. For more information, go to www.medlineplus.gov and type "BRCA" in the Search box.
Now that the BCPT and STAR have shown that SERMs can effectively reduce the risk of developing breast cancer, NCI and NSABP are developing a trial to see if a newer type of drug, called an aromatase inhibitor, can do an even better job of preventing breast cancer than the SERMs. Aromatase inhibitors stop an enzyme called aromatase from turning androgen into estrogen. Investigators are currently in the planning stages of this trial, and enrollment could begin as early as 2007.