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Dutch researchers have developed a method of determining whether a woman’s breast cancer will spread to other organs, according to a report published in a recent issue of the New England Journal of Medicine. The technique involves looking at 25,000 genes within breast cancer tumor cells to determine which genes are "turned on." A certain pattern of active or inactive genes can indicate more aggressive cancers, which typically require more rigorous treatments, such as chemotherapy, in addition to surgery. Though the test is preliminary, it could eventually help physicians decide which patients need aggressive treatments and which do not. Though some early forms of breast cancer are confined to the breast, more advanced forms of the disease have the potential to spread to other areas of the body. Breast cancer usually spreads first to the axillary lymph nodes, located near the armpit. This is why surgeons often remove some or all of these lymph nodes during breast cancer surgery—to help prevent the spread of breast cancer. After the lymph nodes, breast cancer has the potential to spread, or metastasize, to almost any area of the body. The most common regions that breast cancer can spread to, in order of frequency, are the bone, the lung, and the liver. In an attempt to predict which breast cancer patients require aggressive treatments such as chemotherapy in addition to surgery, Marc J. van de Vijver, MD and colleagues from the Netherlands Cancer Institute studied 295 women with breast cancer. All of the women had undergone either mastectomy or lumpectomy to remove their tumors. Using a special type of DNA chip called a microarray, Dr. van de Vijver and his team studied the activity of 25,000 genes within breast cancer cells. The researchers searched in particular for which genes were expressed, or "turned on," within the cancer cells. They found that the activity of 70 genes could determine whether a patient had an aggressive type of breast cancer and was more likely than others to die from the disease. In the study, those women whose genes were turned off or on in a certain pattern were twice as likely to develop breast cancer in another area of the body, and 45% of those women died from the disease within 10 years. By comparison, 85% of the women in the study whose genetic expression did not fall into the pattern remained cancer-free after 10 years of follow-up. Analyzing gene expression in this way allowed the researchers to more accurately determine which women were at high risk of having their cancer spread to other areas of the body compared to the standard means of prediction, which involves assessing factors such as tumor size, patient age, and microscopic features of the tumor. Theoretically, this could reduce the number of patients who need to undergo chemotherapy. The Dutch researchers are one of several groups who are working to develop a method of analyzing gene expression. Researchers from the National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) are also developing a genetic test that enables them to distinguish between hereditary and non-hereditary forms of breast cancer. In a study published in February 2001, Dr. Jeffrey Trent of the NHGRI and colleagues studied 22 breast cancer tumors that had been surgically removed from patients. Of the 22 cancers, 15 were already known to be hereditary from previous analyses (7 were caused by BRCA1 gene mutations and 8 were caused by BRCA2 gene mutations). The other 8 were sporadic breast cancers since no family history of breast cancer existed. After performing "gene expression" profiling, the researchers were able to correctly differentiate between the BRCA1, BRCA2 and non-hereditary forms of breast cancer. (BRCA1 and BRCA2 are two genes that, when found to be mutated, increase a woman’s risk of developing breast and ovarian cancers). For now, this research remains at the preliminary stages. More studies are needed, with patients of varying ages and varying tumor characteristics. Nonetheless, gene expression analysis is becoming an exciting area of research with the potential to one day change the way breast cancer is diagnosed and treated.
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