Universal Genetic Testing vs. Guideline-Directed Testing for Hereditary Cancer Syndromes Among Traditionally Underrepresented Patients in a Community Oncology Program

Jeremy C Jones; Michael A Golafshar; Tucker W Coston; Rohit Rao; Ewa Wysokinska; Elizabeth Johnson; Edward D Esplin; Robert L Nussbaum; Brandie Heald; Margaret Klint; Kathleen Barrus; Pedro L Uson Jr; Cuong C Nguyen; Gerald Colon-Otero; Tanios S Bekaii-Saab; Roxana Dronca; Katie L Kunze; N Jewel Samadder

doi:10.7759/cureus.37428

Universal Genetic Testing vs. Guideline-Directed Testing for Hereditary Cancer Syndromes Among Traditionally Underrepresented Patients in a Community Oncology Program

Cureus. 2023 Apr 11;15(4):e37428. doi: 10.7759/cureus.37428. eCollection 2023 Apr.

Authors

Jeremy C Jones¹, Michael A Golafshar², Tucker W Coston¹, Rohit Rao¹, Ewa Wysokinska¹, Elizabeth Johnson¹, Edward D Esplin³, Robert L Nussbaum³, Brandie Heald³, Margaret Klint⁴, Kathleen Barrus⁴, Pedro L Uson Jr⁵, Cuong C Nguyen⁵, Gerald Colon-Otero¹, Tanios S Bekaii-Saab⁵, Roxana Dronca¹, Katie L Kunze², N Jewel Samadder⁶

Affiliations

¹ Hematology & Oncology, Mayo Clinic, Jacksonville, USA.
² Health Policy, Mayo Clinic, Phoenix, USA.
³ Medical Affairs, Invitae Corporation, San Francisco, USA.
⁴ Clinical Genomics, Mayo Clinic, Phoenix, USA.
⁵ Hematology & Oncology, Mayo Clinic, Phoenix, USA.
⁶ Gastroenterology and Hepatology, Mayo Clinic, Phoenix, USA.

Abstract

Background Detection of pathogenic germline variants (PGVs) has implications for cancer screening, prognosis, treatment selection, clinical trial enrollment, and family testing. Published guidelines provide indications for PGV testing, determined by clinical and demographic factors, but their applicability in an ethnically and racially diverse community hospital population is unknown. This study describes the diagnostic and incremental yield of universal multi-gene panel testing in a diverse population in a community cancer practice. Methods We completed a prospective study of proactive germline genetic sequencing among patients with solid tumor malignancies at a community-based oncology practice in downtown Jacksonville, FL, between June 2020 and September 2021. The patients were unselected for cancer type, stage, family history, race/ethnicity, and age. PGVs identified using an 84-gene next-generation sequencing (NGS) tumor genomic testing platform were stratified by penetrance. National Comprehensive Cancer Networks (NCCN) guidelines determined incremental PGV rates. Results Two hundred twenty-three patients were enrolled, with a median age of 63 years, 78.5% female. 32.7% were Black/African American, and 5.4% were Hispanic. 39.9% of patients were commercially insured, Medicare/Medicaid insured 52.5%, and 2.7% were uninsured. The most common cancers in this cohort were breast (61.9%), lung (10.3%), and colorectal (7.2%). Twenty-three patients (10.3%) carried one or more PGVs, and 50.2% carried a variant of uncertain significance (VUS). Though there was no significant difference in the rate of PGVs based on race/ethnicity, African Americans were numerically more likely to have a VUS reported than whites (P=0.059). Eighteen (8.1%) patients had incremental clinically actionable findings that practice guidelines would not have detected, which was higher in non-whites. Conclusions In this racially/ethnically and socioeconomically diverse cohort, universal multi-gene panel testing (MGPT) increased diagnostic yield over targeted guideline-informed testing. Rates of VUS and incremental PGV were higher in non-white populations.

Keywords: germline testing; hereditary cancer syndromes; homologous recombination deficiency; lynch syndrome; screening strategy.

Grants and funding

The study was funded by Mayo Clinic Center for Individualized Medicine, Desert Mountain Members’ CARE Foundation. The funding sources did not play a role in the study's design, conduct, or reporting or in the decision to submit the manuscript for publication.