Abstract PS18-34: Physician adoption and molecular landscape of next-generation sequencing in breast cancer patients from community-based clinics
Authors: Sturgill Emma , Misch Amanda , Lachs Rebecca , Jones Carissa , Schlauch Dan , Jones Suzanne , Shastry Mythili , Yardley Denise , Burris Howard , Spigel David , Hamilton Erika , McKenzie Andrew 
Published: February 2021

Abstract
Background: Molecular biomarkers such as the expression status of hormone receptors (HR) and HER2 influence disease diagnosis, prognosis, and treatment decisions in breast cancer patients. Recent advances in genetic sequencing technologies and targeted therapies have revealed additional actionable biomarkers including PIK3CA, ESR1, and BRCA1/2; however, it remains unclear whether physicians in community-based clinics are universally adopting molecular profiling practices. Here, we describe the utility of next generation sequencing (NGS) in the care of breast cancer patients in community-based clinics with a focus on physician behaviors and molecular landscapes.
Methods: Sarah Cannon provides clinical research services to medical oncology practices who order NGS panels as part of standard of care. Genospace, Sarah Cannon’s web-based precision medicine platform, links NGS test results with electronic medical records to identify and analyze clinico-genomic data of molecularly-profiled cancer patients. Here, a total of 2,673 NGS reports from 2,313 unique patients dated between January 2014 and December 2019 were analyzed. Hormone statuses were abstracted from physician notes using natural language processing capabilities and manual abstraction. Linear regression modeling was used for statistical analysis.
Results: Physician ordering of NGS tests for breast cancer patients increased 6.3-fold from 2014 to 2019. Ordering of plasma-based NGS tests increased from 0.6% (versus 99.4% tissue) in 2014 to 47.0% (versus 53.0% tissue) in 2019. The time from initial diagnosis to NGS results increased from a median of 1008 days in 2015 to 1296 days in 2019 (p &lt; 0.05), while the time from specimen collection to NGS test results (tissue only) decreased from 53 days in 2015 to 28 days in 2019 (p &lt; 0.01). The majority of NGS-tested breast cancer patients were HR+/HER2- (62.6%), followed by HR-/HER2- (21.5%), HR+/HER2+ (8.4%), HR-/HER2+ (4.4%), and HER2 equivocal (3.0%). Plasma-based NGS testing was utilized more commonly in HR+ cancers (43.4% of HR+; 25.3% of HR-). In agreement with published studies, BRCA1 alterations were enriched in HR- cancers (1.7% of HR+; 6.6% of HR-) and BRCA2 alterations were enriched in HR+ cancers (6.4% of HR+; 3.2% of HR-). Amplifications in CCND1 (21.7% of HR+; 2.2% of HR-) and FGFR1 (18.1% of HR+; 6.2% of HR-) were also enriched in HR+ cancers, as were mutations in ESR1 (18.9% of HR+; 1.0% of HR-). PIK3CA mutations occurred most frequently in HR+ cancers (45.0%), but were also present in HR- cancers (20.9%). TP53 mutations were comparatively high in HR- cancers (42.9% of HR+; 94.8% of HR-).
Conclusions: The usage of NGS for the care of breast cancer patients is increasing in community settings. Plasma-based NGS tests are ordered more frequently in HR+ cancers, likely as a result of difficult-to-biopsy and poor yield bone-only disease. Despite increased testing frequencies, NGS tests are ordered later-in-care which may be a reflection of earlier diagnosis or the development of more efficacious standard of care therapies in front line settings. The tissue specimens sent for sequencing are collected closer to the test date, indicating improved tissue processing systems and prioritization of fresh specimen collection for NGS testing. Overall, physicians are adopting NGS-testing as part of standard of care for breast cancer patients in the community setting and are discovering actionable mutations.
Frequency of detection of molecular biomarkers in NGS-tested breast cancer patientsTissueTissueTissueTissuePlasmaPlasmaPlasmaPlasmaGeneAlterationHR+/HER2-HR-/HER2-HR+/HER2+HR-/HER2+HR+/HER2-HR-/HER2-HR+/HER2+HR-/HER2+ERBB2Amp1.1%0.5%45.4%67.9%0.0%0.8%10.4%45.5%CCND1Amp21.3%1.7%21.8%5.1%7.5%1.7%5.2%0.0%MYCAmp9.3%15.5%18.5%17.9%1.3%5.8%1.3%9.1%FGFR1Amp17.4%6.8%18.5%3.8%6.5%3.3%2.6%0.0%PIK3CAMutation43.8%19.1%49.6%32.1%49.5%25.0%50.6%30.3%ESR1Mutation19.4%1.2%13.4%0.0%41.7%4.2%31.2%0.0%BRCA1Mutation1.9%7.2%0.8%3.8%5.1%5.0%2.6%9.1%BRCA2Mutation6.7%3.6%5.9%1.3%8.8%5.8%14.3%3.0%ERBB2Mutation3.4%1.4%11.8%6.4%9.5%1.7%15.6%12.1%TP53Mutation42.2%94.7%51.3%93.6%65.8%96.7%68.8%93.9%PTENMutation8.8%10.6%2.5%3.8%12.6%10.8%7.8%6.1%PALB2Mutation1.6%1.2%0.8%0.0%0.2%0.0%0.0%0.0%MTORMutation0.7%0.2%0.8%0.0%2.7%0.0%0.0%0.0%ARID1AMutation9.0%4.8%12.6%2.6%11.0%11.7%7.8%3.0%KRASMutation3.2%3.1%0.8%2.6%6.5%8.3%5.2%6.1%AKT1Mutation6.5%3.4%2.5%1.3%7.5%6.7%1.3%0.0%n=856n=414n=119n=78n=602n=120n=77n=33
Citation Format: Emma Sturgill, Amanda Misch, Rebecca Lachs, Carissa Jones, Dan Schlauch, Suzanne Jones, Mythili Shastry, Denise Yardley, Howard Burris, David Spigel, Erika Hamilton, Andrew McKenzie. Physician adoption and molecular landscape of next-generation sequencing in breast cancer patients from community-based clinics [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-34.