Abstract PD14-07: PD14-07 Associations of Breast Cancer Risk Level and Prediction of Tumor Aggressiveness in the Athena Breast Health Network
Authors: Leggat-Barr Katherine , Lewis Tomiyuri , Sayaman Rosalyn , Warner Paige , Malvin Kathy , Sabacan Leah , Tsopurashvili Elene ,   WISDOM Study and Athena Breast Health Network Investigators and Advocate Partners, MPH, Fiscalini Allison Stover , Tice Jeffrey , Kerlikowske Karla , Shieh Yiwey , Esserman Laura J. , Van ’t Veer Laura 
Published: March 2023

Abstract
Background: The Athena Breast Health Network (Athena) is a University of California (UC) initiative integrating clinical care and research to drive improvements in breast cancer screening. Through standardized, self-reported clinical intake forms, a patient’s breast health status and information regarding their breast cancer risk is captured before each mammography appointment. Breast cancer risk models provide a level of risk to develop breast cancer but do not take into account aggressiveness of breast cancer. Here, we evaluated outcome data of a large screening cohort for association between risk level and aggressiveness at diagnosis. Methods: We calculated Breast Cancer Surveillance Consortium (BCSC) risk scores for a cohort of 8,923 consented UCSF Athena participants from the years 2012-2018 with a median follow-up of 5-years. To identify those who developed invasive breast cancer on or after completing an Athena intake form, we performed a cancer linkage with the San Francisco Mammography Registry (SFMR), a local registry that regularly collects cancer data from the California Cancer Registry. We classified tumors as aggressive if they met one or more of the following criteria: hormone receptor (HR)-negative, HER2-positive, grade 3. All other tumors were classified as non-aggressive. We used student’s t-tests to examine associations between BCSC 5-year risk score, the development of invasive breast cancer, and tumor aggressiveness among cases. To account for the association between older age and higher BCSC risk score (as well as HR-positive subtypes), we stratified by percentiles of BCSC risk by age (top 2.5% vs. bottom 97.5%). The top 2.5% by age threshold consistently identifies women with lifetime risk of 23–28% and was chosen as high-risk threshold to trigger annual screening in the WISDOM study (Dreher: PMID34843026). Results: Of 8,923 participants, 170 (2%) developed breast cancer during the follow-up period. The average 5-year BCSC risk score for women with breast cancer was 1.81% and 1.47% for those without (p&lt; 0.001). Among women with breast cancer, 123 (72%) developed non-aggressive cancers and 47 (28%) developed aggressive cancers. The average 5-year BCSC risk score for women with non-aggressive and aggressive cancers was 1.89% and 1.60%, respectively (p=0.13). In analyses stratified by percentile of BCSC risk by age, 521 (6%) participants had a BCSC 5-year risk score in the top 2.5% by age and 8,402 (94%) participants had a BCSC 5-year risk score in the bottom 97.5%. A higher percentage of women with non-aggressive cancers vs healthy women (controls) were in the top 2.5% by age (p = 0.001), but the percentage of aggressive cancers vs healthy women in the top 2.5% by age was similar (p = 0.61). Conclusion: Through this study we confirmed that higher 5-year BCSC risk scores are associated with higher overall breast cancer development. Interestingly, participants with the highest 5-year BCSC risk scores (top 2.5% by age), are more likely to develop cancers with non-aggressive features (low grade, hormone positive). This suggests that the BCSC model may preferentially predict less aggressive tumors, and those with the highest 5-year BCSC risk may be more likely to benefit from endocrine risk reduction therapy. There remains a gap in our ability to identity those at risk for aggressive cancers. Our findings highlight the need for screening programs to better understand who is at risk for what type of breast cancer. Current work is focused on developing models tailored to risk prediction of aggressive cancers.
Citation Format: Katherine Leggat-Barr, Tomiyuri Lewis, Rosalyn Sayaman, Paige Warner, Kathy Malvin, Leah Sabacan, Elene Tsopurashvili, WISDOM Study and Athena Breast Health Network Investigators and Advocate Partners, Allison Stover Fiscalini, Jeffrey Tice, Karla Kerlikowske, Yiwey Shieh, Laura J. Esserman, Laura Van ’t Veer. PD14-07 Associations of Breast Cancer Risk Level and Prediction of Tumor Aggressiveness in the Athena Breast Health Network [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD14-07.