CLINICAL Testing for Hereditary Breast UPDATE and Ovarian Cancer Syndrome VOL.5 NO.6

Red Flags for BRCA Mutations Found in Women with Little or No Family History Hereditary Breast and Hereditary Breast and Ovarian Cancer Syndrome is caused by mutations in the BRCA1 and BRCA2 genes. Because these mutations can be inherited Ovarian Cancer Syndrome through either the maternal or the paternal side of the family and family Personal or family history of: history of cancer may be lacking due to a small family structure, researchers have found that a significant proportion of BRCA1 and BRCA2 mutation ᮣ Breast cancer before age 50 carriers do not have a family history of breast or ovarian cancer.1,2 The ᮣ Ovarian cancer at any age authors of the following study examined the prevalence of BRCA1 and BRCA2 mutations in women with early onset breast cancer in which there was no ᮣ Bilateral breast cancer family history of breast or ovarian cancer. ᮣ Both breast and ovarian Weitzel, et al. Limited family structure and BRCA gene mutation status in cancer in an individual single cases of breast cancer. JAMA. 2007 Jun 20;297(23):2587-95. ᮣ Male breast cancer at any age Purpose: To examine the prevalence of BRCA gene mutations among single cases ᮣ Women of Ashkenazi Jewish of early onset breast cancer within a limited family structure compared to descent with breast or families with adequate structure. ovarian cancer at any age Design and Methods: Of 1543 women presenting for genetic testing for BRCA1 ᮣ Breast cancer in two or and BRCA2 mutations, 306 were diagnosed under the age of 50 and reported more relatives no family history of breast or ovarian cancer. Family structure was considered limited when there were fewer than two first- or second-degree female ᮣ A previously identified relatives surviving past the age of 45 in either the maternal or paternal side BRCA1 or BRCA2 mutation of the family. Of the 306 families included in the study, 153 (50%) were in the family considered to have a limited family structure. Myriad Genetic Laboratories, Inc. Results: Of the 306 women meeting the inclusion criteria of this study, 29 (9.5%) has easy to use tools that can women were found to carry a mutation in BRCA1 or BRCA2. When stratified by family history structure, 21 of 153 (13.7%) women with a limited family assist you in identifying these structure were found to carry mutations. Over 75% of these mutation carriers patients in your practice. To would have been missed using the risk prediction models currently available. discuss the patient identification Prevalence of BRCA1 and BRCA2 Mutations in Isolated Early Onset Breast Cancer options that will work for your # of families Mutation carriers practice, please contact your local Myriad representative for Limited family structure 153 13.7% more information. Overall 306 9.5%

Bottom Line: While knowing the family history of individuals with breast cancer is important, family history cannot be used solely to determine eligibility for testing. Nearly 14% of women with isolated breast cancer under 50 whose family history structure is limited carried mutations in BRCA1 and BRCA2. Thus, women with breast cancer diagnosed before the age of 50 years, regardless of family history, are appropriate candidates for testing for hereditary breast and ovarian cancer syndrome. 1. Science 2003;302:643-6. 2. Cancer 2005;104(12):2807-16.

For more information regarding the content Myriad Genetic Laboratories, Inc. in this newsletter, please contact your local 320 Wakara Way, Salt Lake City, UT 84108-9930 Myriad Representative. For more information: 1-800-469-7423 FAX 1-801-584-3615 www.myriadtests.com ©2004-07, Myriad Genetic Laboratories, Inc.

Myriad, the Myriad logo, and BRACAnalysis are either trademarks or registered trademarks of Myriad Genetics, Inc. in the United States and other jurisdictions.