Allison W Kurian1, Paul Abrahamse2,3, Kevin C Ward4, Ann S Hamilton5, Dennis Deapen5, Jonathan S Berek6, Lily Hoang7, Amal Yussuf7, Jill Dolinsky7, Krystal Brown8, Thomas Slavin8, Timothy P Hofer9, Steven J Katz9. 1. Departments of Medicine and of Epidemiology & Population Health, Stanford University, Stanford, CA. 2. Department of Health Management and Policy, School of Public Health, University of Michigan, Ann Arbor, MI. 3. Department of Biostatistics, University of Michigan, Ann Arbor, MI. 4. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA. 5. Department of Preventive Medicine in the Keck School of Medicine, University of Southern California, Los Angeles, CA. 6. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, and Stanford Women's Cancer Center, Stanford University, Stanford, CA. 7. Ambry Genetics, Aliso Viejo, CA. 8. Myriad Genetics, Salt Lake City, UT. 9. Department of Internal Medicine, University of Michigan and Center for Clinical Management Research, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI.
Abstract
PURPOSE: Family cancer history is an important component of genetic testing guidelines that estimate which patients with breast cancer are most likely to carry a germline pathogenic variant (PV). However, we do not know whether more extensive family history is differentially associated with PVs in specific genes. METHODS: All women diagnosed with breast cancer in 2013-2017 and reported to statewide SEER registries of Georgia and California were linked to clinical genetic testing results and family history from two laboratories. Family history was defined as strong (suggestive of PVs in high-penetrance genes such as BRCA1/2 or TP53, including male breast, ovarian, pancreatic, sarcoma, or multiple female breast cancers), moderate (any other cancer history), or none. Among established breast cancer susceptibility genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D, and TP53), we evaluated PV prevalence according to family history extent and breast cancer subtype. We used a multivariable model to test for interaction between affected gene and family history extent for ATM, BRCA1/2, CHEK2, and PALB2. RESULTS: A total of 34,865 women linked to genetic results. Higher PV prevalence with increasing family history extent (P < .001) was observed only with BRCA1 (3.04% with none, 3.22% with moderate, and 4.06% with strong history) and in triple-negative breast cancer with PALB2 (0.75% with none, 2.23% with moderate, and 2.63% with strong history). In a multivariable model adjusted for age and subtype, there was no interaction between family history extent and PV prevalence for any gene except PALB2 (P = .037). CONCLUSION: Extent of family cancer history is not differentially associated with PVs across established breast cancer susceptibility genes and cannot be used to personalize genes selected for testing.
PURPOSE: Family cancer history is an important component of genetic testing guidelines that estimate which patients with breast cancer are most likely to carry a germline pathogenic variant (PV). However, we do not know whether more extensive family history is differentially associated with PVs in specific genes. METHODS: All women diagnosed with breast cancer in 2013-2017 and reported to statewide SEER registries of Georgia and California were linked to clinical genetic testing results and family history from two laboratories. Family history was defined as strong (suggestive of PVs in high-penetrance genes such as BRCA1/2 or TP53, including male breast, ovarian, pancreatic, sarcoma, or multiple female breast cancers), moderate (any other cancer history), or none. Among established breast cancer susceptibility genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D, and TP53), we evaluated PV prevalence according to family history extent and breast cancer subtype. We used a multivariable model to test for interaction between affected gene and family history extent for ATM, BRCA1/2, CHEK2, and PALB2. RESULTS: A total of 34,865 women linked to genetic results. Higher PV prevalence with increasing family history extent (P < .001) was observed only with BRCA1 (3.04% with none, 3.22% with moderate, and 4.06% with strong history) and in triple-negative breast cancer with PALB2 (0.75% with none, 2.23% with moderate, and 2.63% with strong history). In a multivariable model adjusted for age and subtype, there was no interaction between family history extent and PV prevalence for any gene except PALB2 (P = .037). CONCLUSION: Extent of family cancer history is not differentially associated with PVs across established breast cancer susceptibility genes and cannot be used to personalize genes selected for testing.
Authors: Allison W Kurian; Kevin C Ward; Ann S Hamilton; Dennis M Deapen; Paul Abrahamse; Irina Bondarenko; Yun Li; Sarah T Hawley; Monica Morrow; Reshma Jagsi; Steven J Katz Journal: JAMA Oncol Date: 2018-08-01 Impact factor: 31.777
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Authors: Thomas S Frank; Amie M Deffenbaugh; Julia E Reid; Mark Hulick; Brian E Ward; Beth Lingenfelter; Kathi L Gumpper; Thomas Scholl; Sean V Tavtigian; Dmitry R Pruss; Gregory C Critchfield Journal: J Clin Oncol Date: 2002-03-15 Impact factor: 44.544
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