Abstract P3-07-03: Real-world evidence database reveals 17.74% of individuals with breast cancer harbor a germline pathogenic or likely-pathogenic variant with implications for medical management and/or reproduction
Authors: Bontempo Kelly , Wernecke Chloe , Mauer Caitlin , Bentley Brenna , Graham Maureen , Whitworth Pat , Patel Rakesh , Beitsch Peter 
Published: March 2022

Abstract
Background:Uncovering germline genetic variants responsible for cancer predisposition allows providers to implement personalized medical care for patients. Guidelines were designed to help identify individuals who qualify for genetic testing, yet multiple studies have shown that approximately half of patients with P/LP variants are missed using these guidelines. While guidelines have continued to evolve as more robust data have become available, patients who do not meet these guidelines may not be identified as having a cancer predisposition syndrome. In studies focusing on patients with multiple cancer subtypes, comparisons of universal genetic testing versus guideline-directed for patients revealed a 12.5% likelihood of a pathogenic germline variant. This has also been studied specifically in patients with colorectal cancer, revealing that 15.5% of affected individuals have an identifiable pathogenic variant. As research continues to evaluate universal testing in oncology, it is increasingly evident that we are approaching pathogenic variant carrier frequencies that argue for a more aggressive expansion of guidelines. This has been the catalyst for recommending germline genetic testing for all patients with breast cancer. However, as insurance companies and national guidelines do not yet support this recommendation, here we set out to examine the mutation rate in all patients with breast cancer versus patients with breast cancer diagnosed at or before age 65 years. Methods:Patient data was obtained from the Informed Genetics Annotated Patient Registry (iGAP), an IRB-approved multi-center longitudinal, observational study designed to capture genetic and genomic test results and their utilization and impact on treatment practices and outcomes. Descriptive statistics were used to assess and compare data of these populations and germline genetic testing results. Results:Of the 1,302 subjects currently enrolled in the registry, 1,132 have been diagnosed with any cancer type (86.89%), of which 868 have specifically been diagnosed with breast cancer (76.657%). Results indicate that 19.04% of individuals (1 in 4.56) with any cancer type have a germline pathogenic or likely-pathogenic variant associated with cancer predisposition and/or implications for reproduction. Specific to breast cancer, results indicate that 17.74% of individuals (1 in 5.6) harbor a germline pathogenic or likely-pathogenic variant with these same implications. Of the patients with breast cancer, 71.54% were diagnosed prior to age 65 years, while 28.45% were diagnosed at or above age 65 years. 108 patients diagnosed before age 65 years had a P/LP (70.12%) while 46 diagnosed at or above age 65 years had a P/LP variant (29.87%). Conclusion:The iGAP real-world evidence database reveals 17.74% (1 in 5.6) of individuals with breast cancer harbor a pathogenic or likely-pathogenic variant in the germline with implications for medical management and/or reproduction. Given the implications these results can have on patients’ and family members’ health, testing guidelines for breast cancer should be expanded so those with hereditary predispositions can be identified and make informed decisions about preventative measures to reduce risks for a second cancer and overall mortality. Identifying those pathogenic/likely-pathogenic variants also allows for cascade testing of at-risk, likely unaffected relatives, helping reduce overall cancer incidence in the general population. Additionally, since cancer predisposition genes can also confer reproductive implications related to autosomal recessive disorders, expanding testing guidelines can arm patients with additional information that can aid in reproductive decision making.
Citation Format: Kelly Bontempo, Chloe Wernecke, Caitlin Mauer, Brenna Bentley, Maureen Graham, Pat Whitworth, Rakesh Patel, Peter Beitsch. Real-world evidence database reveals 17.74% of individuals with breast cancer harbor a germline pathogenic or likely-pathogenic variant with implications for medical management and/or reproduction [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-07-03.