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Although the breast cancer susceptibility genes, BRCA1 and BRCA2, are similar, researchers have found significant differences in the genetic profiles of cancers that result from mutations of these genes, according to a study recently published in the New England Journal of Medicine.

Breast cancer is the second leading cause of cancer death in women in the United States, with approximately 200,000 cases diagnosed each year. Although several risk factors have been associated with breast cancer, the cause of the majority of cases of breast cancer remains unknown.

Mutations in the BRCA1 and BRCA2 genes substantially increase the risk of developing breast cancer. The lifetime risk estimate for developing breast cancer in the general population is 12%, whereas the risk for individuals with BRCA1 or BRCA2 mutations is 50 to 85%. While both genetic mutations confer an increased risk, the cancers that result from these mutations are different. Usually BRCA2 mutations lead to estrogen receptor-positive breast cancer, whereas BRCA1 mutations lead to estrogen receptor-negative breast cancer. These differences indicate inherent differences in the genes.

Researchers from the National Institutes of Health examined the genetic components of tumors from 21 women: 7 with BRCA1 mutations, 7 with BRCA2 mutations and 7 with sporadic breast cancer. The researchers then evaluated and compared the genetic profiles from the different types of tumors. They found that the biological characteristics of the tumors were significantly different depending on which type of genetic mutation caused the tumor.

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The researchers concluded that an inherited mutation influences the gene-expression profile of the cancer. The results of this study have serious implications for the future treatment of breast cancer because the information could lead to individualized treatment for different types of breast cancer that have historically been treated as the same.

More research is needed to further define the implications of using genetic profiles to understand the development of different types of cancers. As researchers continue to explore the molecular differences among cancers, they work toward a greater understanding of how and why different types of cancers arise in individuals who carry these and other genetic mutations. To learn more about genetic testing, go to (New England Journal of Medicine, Vol 344, No 8, pp. 539-548, 2001)

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