The study used precancerous breast cells from patients with Li-Fraumeni syndrome (LFS), a hereditary cancer predisposition syndrome associated with a number of childhood cancers and the early onset of breast cancer. Unlike most human cancer cells, LFS cells become cancerous at more measurable rates in vitro (a closed environment, e.g. test tube), and are therefore easier to monitor. Individuals with LFS are at increased risk for developing multiple primary cancers, including soft-tissue sarcoma, breast cancer, leukemia, osteosarcoma, melanoma and colorectal cancers.
"To effectively treat or prevent cancer, it is important to understand the nature of how cells progress into the disease," explained Brittney-Shea Herbert, Ph.D., cell biologist at The University of Texas Southwestern Medical Center, Dallas, and lead investigator of the study. "Results from human clinical trials take many years to generate so it is imperative that alternate testing forms, such as precancerous cells, be used to determine the effectiveness of precancerous agents."
Treatment of precancerous LFS breast cells with some but not all chemopreventive agents decreased the development of cancer in vitro. The chemopreventive agents used in this study did not negatively affect normal cell growth, nor result in notable side effects from the treatment. Tamoxifen had the strongest effect in preventing the frequency of cell immortalization, at nontoxic levels.
Precancerous cells were treated with tolerable levels of tamoxifen, nonsteriodal anti-inflammatory drugs (NSAIDS), a preoxisome proliferator-activated receptor ã (PPAR-ã) agonist, and the p53-rescue drug (CP31398), which reactivates the gene that suppresses tumor growth (p53). Treatment with CP31398 had the greatest effect in stopping the immortalization of cancer development, compared to the untreated or solvent controls. PPAR-ã agonist and CP31398 slowed the progression of the cancer; NSAIDS had a marginal effect, but it was not statistically significant. Immortalization is a critical step for cancer progression and validates the use of in vitro models.
More than 203,500 new cases of breast cancer will be diagnosed and more than 39,600 women will die in 2002, according to the American Cancer Society. Breast cancer is the second leading cause of cancer-death in women.
Founded in 1907, the American Association for Cancer Research (AACR) is a professional society of more than 19,000 laboratory and clinical scientists engaged in cancer research in the United States in more than 60 other countries. AACR's mission is to accelerate the prevention and cure of cancer through research, education, communication and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals (Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention).