Combining Tyrer-Cuzick, germline testing, and polygenic risk scores identified 677 high-risk breast cancer patients missed by TC alone for management changes.
Does a combined approach of family history, germline testing, and MA-PRS identify more high-risk patients requiring management changes compared to Tyrer-Cuzick alone in patients presenting for mammograms?
A comprehensive risk assessment including germline testing and polygenic risk scores identifies significantly more patients at high risk for breast cancer who require management changes compared to standard clinical models alone.
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Abstract Background: To evaluate the effectiveness of using Tyrer-Cuzick version 8 (TCv8, herein referred to as TC) alone compared to a combined approach of a family history assessment, germline testing, and TC with a breast cancer (BC) multiple ancestry polygenic risk score (MA-PRS), in identifying patients at high risk for breast and other cancers at imaging centers. Here we compared approaches for identifying high-risk patients to improve personalized screening and management. Methods: In November 2020, Singing River Health System launched a comprehensive breast program using the TC risk model and germline testing with MA-PRS to identify high-risk patients. During mammogram visits, patients completed the TC risk model and were assessed for genetic testing eligibility based on NCCN guidelines using a cancer history questionnaire. Eligible patients received a comprehensive family history intake and education by telephone from a genetic counselor and, if consented, had blood drawn for genetic testing the same day. The testing included a laboratory’s, a laboratory’s multi-gene panel and MA-PRS to determine BC risk and hereditary cancer syndromes. Post-testing, a nurse navigator reviewed the results and counseled patients on appropriate next steps. We evaluated results to identify guideline-recommended management changes and to determine if high-risk patients would not have been identified without germline testing and MA-PRS. Results: From November 2020 through December 2023, a total of 2,434 patients completed TC and if they met the criteria for genetic testing at the time of their mammogram, they had multi-gene panel testing and MA-PRS. Within this cohort, 677 patients had a TC 20% lifetime BC risk, yet were candidates for medical management change based on their genetic testing, MA-PRS, and/or comprehensive family history results. Specifically, 70 patients with TC 20% met the criteria for genetic testing and were found to carry pathogenic variants in genes associated with hereditary cancer syndromes. Additionally, 133 patients with TC 20% had a BC risk 20% due to the incorporation of MA-PRS. Furthermore, 474 patients with TC 20% were appropriate for modification in management strategy based on family history information obtained through patient education intake. Conclusions: A detailed risk assessment and testing program involving TC, a polygenic risk score model, and germline testing at a community imaging center identified more high-risk individuals and suggested alterations in screening and management compared to using TC alone. Without this approach, patients at elevated cancer risk requiring management changes may not have been recognized. Citation Format: T. McKamie, T. Hudson, L. Brzeskiewicz, S. Cummings. Enhancing breast cancer risk assessment in a community imaging center to identify high-risk patients and guide screening and management abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-02-13.
McKamie et al. (Tue,) reported a other. Combining Tyrer-Cuzick, germline testing, and polygenic risk scores identified 677 high-risk breast cancer patients missed by TC alone for management changes.