Abstract A020: Impact of universal germline testing on pathogenic/likely pathogenic variant frequency among breast cancer patients in Southern California
Authors: Dzubnar Jessica , Wang Yongzhe , Aljaber Dana , Quinones Christine , Tseng Jennifer , Solomon Ilana , Gonzalez Lorena , Gray Stacy , Jones Veronica 
Published: September 2024

Introduction Since 2020, the Precision Medicine Initiative has provided no cost germline and testing to all patients with solid tumors. We sought to measure the impact of this initiative on germline mutation frequency in breast cancer (BC) patients across multiple social determinants of health. Methods The electronic health record was queried for patients diagnosed with BC between 2020 and 2024 at our Southern California clinical network sites who had germline testing through the Precision Medicine Initiative. Frequency of pathogenic/likely pathogenic variants (P/LPV) was stratified by age, race/ethnicity, preferred language, insurance status, zip code, and molecular subtype. Fisher’s exact testing and multivariate logistic regression were carried out to identify significant interactions. Mapping was conducted to identify the geographical spectrum of variants. Results Between 2020 and 2024, 1,760 BC patients underwent germline testing. Geographical mapping revealed genetic testing spanning 620 miles. Half of patients had public health insurance (n=908, 51.59%). The majority were between the ages of 55 and 75 (n=952, 54.09%), and 5% were &lt;39 years old (n=89). The racial/ethnic distribution of patients included 43.98% non-Hispanic White (NHW) (n=774), 4.66% non-Hispanic Black (NHB) (n=82), 30.23% Hispanic (n=532), and 13.81% Asian (n=243) patients. The majority had English as their chosen preferred language (n=1503, 85.4%). Most patients had luminal A breast cancer (n=838, 47.6%), followed by luminal B (n=284, 16.14%), basal (n=166, 9.43%), and HER2 enriched (n=73, 4.15%). The most commonly mutated genes were BRCA2 (n=45, 2.61%) followed by CHEK2 (n=31, 1.80%), ATP7B (n=29, 1.69%), and BRCA1 (n=28, 1.63%). Other breast cancer high risk genes were less frequent, including PALB2 (n=18, 1.05%), ATM (n=14, 0.81%), and TP53 (n=8, 0.46%). Patients with public insurance were three times more likely to have a BRCA1 mutation than those with private insurance (OR 3.14, 95% CI: 1.06, 10.22). While NHB patients were more likely to have BRCA1 mutation, this did not reach statistical significance. There were significant differences in P/LPV rates across ethnicities among CHEK2 (p=0.028) and CFTR (p=0.017) with these being most common among the NHW patients. On multivariate logistic regression, we observed that NHW patients had a significantly higher percentage of CHEK2 mutations compared to other race/ethnicity groups. 11.76% of the patients with FANCA mutation preferred a language other than English, Spanish or Mandarin (p=0.0385). Conclusions Universal germline testing allows patients otherwise limited by insurance status or distance to undergo testing. Those with public insurance, independent of race, were more likely to have a BRCA1 mutation. Mitigating insurance and geographical barriers may identify additional patients who would benefit from risk reducing techniques and novel targeted therapies.

Citation Format: Jessica Dzubnar, Yongzhe Wang, Dana Aljaber, Christine Quinones, Jennifer Tseng, Ilana Solomon, Lorena Gonzalez, Stacy Gray, Veronica Jones. Impact of universal germline testing on pathogenic/likely pathogenic variant frequency among breast cancer patients in Southern California [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A020.