Perspectives on Clinical Oncogenomics: Secondary Germline Variants Associated With Tumor Genomic Profiling in Community Cancer Care and Advanced Practitioner Oncogenomic Proficiency

Precision medicine in oncology is defined by the sequencing of tumor genomic variants that can be used to identify targeted treatment for patients. Secondary pathogenic and likely pathogenic germline variants (P/LPGVs) can incidentally be detected on tumor genomic profiling (TGP). With the rise in precision medicine over the past 15 years, secondary P/LPGVs on TGP have been an increasingly important clinical issue. However, there are factors that can lead to misidentification and underreporting of P/LPGVs. Germane to this clinical practice issue is healthcare provider oncogenomic literacy and proficiency. A scoping review was conducted to evaluate the variability of the prevalence of P/LPGVs on TGP in patients with solid tumor malignancy. Sixteen articles published between 2016 and 2024 were included in the review with considerable variability noted in the prevalence of P/LPGVs. Potential factors contributing to the variability included the numbers of cancer susceptibility genes and tumor types included, and population size. Next, a retrospective review studied the concordance rate between P/LPGVs on TGP and confirmatory germline testing at two community cancer centers. A high concordance rate of P/LPGVs was observed between the two types of testing, indicating that TGP can help identify cancer susceptibility genes in patients whether they qualify for hereditary cancer syndrome screening or not. The identification of P/LPGVs on TGP does require follow-up confirmatory germline testing in these patients. Secondary analyses were completed of off-tumor genotype-phenotype correlations and variant allele frequency of P/LPGVs on TGP. A quasi-experimental pretest posttest study evaluated advanced practitioners practicing in hematology/oncology regarding self-reported oncogenomic training and proficiency concepts at baseline. The proficiency concepts were reassessed after the intervention of an educational module. The study results indicate that an educational module is one way to address a perceived lack of oncogenomics training and proficiency by APs. Advanced practitioners are integral to oncology care and therefore require adequate training and knowledge to provide comprehensive cancer care to patients.