The results pose new questions regarding the best treatments for women with breast cancer with certain genetic alterations
Researchers at Jefferson Medical College have found a biological marker that may help predict the return of breast cancer in some women. The scientists, led by Bruce Turner, M.D., Ph.D., assistant professor of radiation oncology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, found larger amounts of a damaged anticancer gene, p53, and its protein, in tissue of women whose breast cancer returned within four years after diagnosis than in those women whose cancer did not return. The finding may affect the types of treatments offered such women who are at greater risk for their cancer coming back. Dr. Turner and his colleagues at Jefferson and at Yale University School of Medicine report their work in March in the journal Cancer.
"Women with a genetic change in this important gene may need to be treated with additional therapies necessary to prevent the development of recurrent breast cancer and minimize the risk of metastatic disease," he says. Some of these treatments may include higher doses of radiation and some novel therapies aimed at making cancerous tumors more sensitive to treatment. "The results provide the first evidence in humans that p53 gene changes are also associated with poor responses to radiation therapy treatments," says Dr. Turner.
In the study, Dr. Turner and his group hoped to identify molecular markers that might be useful in predicting those women at increased risk of their cancer returning. They looked at 121 women with early stage breast cancer who were treated surgically between 1973 and 1995 to remove the cancerous lump of tissue in the breast, in addition to receiving radiation. Dr. Turner and his group continued to follow the patients for an average of more than 14 years.
They found that 39 percent of women with breast cancer whose disease returned within four years of diagnosis had higher levels of an altered p53 protein compared to only 9 percent of women whose cancer did not come back. What's more, only 48 percent of the women with high p53 levels lived for 10 years without disease compared to 67 percent who lived disease-free for a decade and did not have any genetic changes in p53.
The p53 gene, a so-called "tumor suppressor," normally helps prevent cancer cells from taking hold. It is important in controlling cell growth, and regulates the actions of many other genes as well. It plays a critical role in cell death.
With the completion of the sequencing of the human genome now two or three years away, Dr. Turner says, studies to determine the best cancer therapies based on specific genetic changes will be critical. In breast cancer, for example, specific radiation and chemotherapy treatments will be determined by certain genetic changes involving perhaps 10,000 to 20,000 genes. "Both pharmaceutical and biotechnology firms are investing heavily in the field of pharmacogenetics with the eventual hope of translating specific genetic changes -- which will become easily identifiable -- into rational therapeutics for all diseases including cancer," he says.
Breast cancer is the most common cancer among women and the second most deadly. The American Cancer Society estimates that 175,000 women will be diagnosed with breast cancer this year and more than 43,000 will die from the disease.
Journal
Cancer