Abstract P3-08-06: Breast cancer patients categorized as high-risk of recurrence and/or basal-type molecular subtype by MammaPrint and BluePrint, respectively, should universally undergo germline genetic testing
Authors: Brenna G Bentley, Chloe Wernecke, Kelly Bontempo, Maureen Graham, Pat Witworth, Rakesh Patel, Peter Beitsch
Journal: Cancer Research (2022)

Abstract Background: Each year there are approximately 281,550 new cases of breast cancer.1 With the rise of somatic testing, more physicians are using panels to understand the genetic profile of breast cancer to help aid in clinical management. Agenida, a molecular diagnostics company focused on breast cancer, has developed two tests to support clinical decisions. MammaPrint analyzes 70 genes associated with breast cancer recurrence and reports whether an individual has a low (1.3%) or high (11.7%) risk for recurrence. BluePrint analyzes 80 genes to identify the breast cancer’s molecular subtype: Luminal A (low-risk), Luminal B (high-risk), HER2 (respond well to HER2-targeted therapies), and Basal-Type (aggressive subtype). However, little is known about the relationship between the results of Agendia’s tests and the likelihood of identifying an underlying germline variant. We hypothesize that individuals in the High-Risk category on MammaPrint, and individuals with Basal subtype are more likely to have positive germline genetic results indicating the presence of a pathogenic or likely pathogenic variant. Methods: Patient data was obtained from the Informed Genetics Annotated Patient Registry (iGAP), an IRB-approved multi-centered longitudinal, observational study designed to capture genetic and genomic test results and their utilization and impact on treatment practices and outcomes to help determine the most effective use of testing in real-world patient populations and to support access to advances in precision medicine. Of the 1,302 subjects currently enrolled in the registry, 868 have been diagnosed with breast cancer (66.67%). 170 individuals underwent tumor profiling through Agendia’s MammaPrint and BluePrint tests as well as germline genetic testing. Descriptive statistics were used to assess and compare data of these populations. Results: Results indicate that of the 170 individuals who were tested through Agendia’s MammaPrint and BluePrint panels and underwent germline genetic testing, 80 (46.47%) were classified as High-Risk for recurrence on MammaPrint, and 90 (53.53%) were identified as having a Low-Risk for recurrence. Individuals with a high-risk of recurrence had an 18.75% positive germline variant rate compared to the low-risk group with a 12.22% positive rate. 170 individuals with breast cancer were tested and categorized through Agendia’s BluePrint panel. 19 were classified as Basal type, 2 as HER2 type, 90 as Luminal A type, and 50 as Luminal B type. Individuals with Basal type had the highest positive germline rate of 26.32%, compared to HER2 (0%), Luminal A (12.22%), and Luminal B (16.29%).Conclusion: The iGAP real-world evidence database revealed that individuals categorized as having a high risk of breast cancer recurrence through Agendia’s MammaPrint were identified to harbor a pathogenic or likely pathogenic variant 18.75% of the time. An even higher likelihood (26.32%) was seen in individuals with a Basal-Type molecular subtype. This data argues that germline genetic testing should be offered to every individual, regardless of age, identified as having a high risk of breast cancer recurrence and/or a basal-type molecular subtype on Agendia’s tests. Identification of a pathogenic or likely pathogenic variant has clinical management, familial, and potentially reproductive implications. References American Cancer Society, 2021. Citation Format: Brenna G Bentley, Chloe Wernecke, Kelly Bontempo, Maureen Graham, Pat Witworth, Rakesh Patel, Peter Beitsch. Breast cancer patients categorized as high-risk of recurrence and/or basal-type molecular subtype by MammaPrint and BluePrint, respectively, should universally undergo germline genetic testing [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 P3-08-06.