THREE USES OF GENETIC TESTING
Genetic testing is useful in three areas of cancer practice.
ONE: Determination of targeted, or precision, therapy in patients with newly diagnosed or recurrent cancer. Both tumor next generation sequencing (NGS) and circulating tumor DNA (ctDNA) NGS are employed for this indication. Most oncology practitioners are already using tumor sequencing in daily practice, although some do not possess a firm understanding of the underlying genetic principles that allow for interpretation beyond the templated information provided in the test results report.
The more useful approach of paired tumor-germline testing is not yet widely performed. Germline variants are present in the tumor and are usually the initiating molecular event in tumor formation for high penetrance, lineage-appropriate tumors (e.g., triple negative breast cancer and BRCA1/2 variants). Alterations in the same genes may be present only in tumor, and lead to uncertainty about their origin. Molecular signatures such as HRD (homologous recombination repair defect) can be seen in tumor as a result of germline or sporadic genetic events. Several FDA indications include germline status as a basis for approval. Thus, paired testing can improve the understanding of hereditary risk and can influence treatment choices.
Two other crucial areas of genetic testing in cancer practice have received much less attention.
TWO: Risk reduction, early detection, and family member risk analysis. About 10-15% of cancers are due to a monogenic, germline (i.e., constitutional) inactivating variant in a tumor suppressor gene (e.g., MLH1) or less commonly to constitutional activation of an oncogene (e.g., RET). Once identified in a person with a cancer diagnosis or in a close family member with cancer, a germline variant can be used to inform treatment of a cancer and manage risk of second cancers in these individuals. Surveillance can identify cancers in family members who are as yet unaffected carriers, and risk reducing surgeries can be life saving. cfDNA testing in blood can now be used to identify a previously undetected cancer. Most oncology practitioners do not conduct germline testing in daily practice, and there is a significant need for education and program development in this area.
THREE: Post-treatment surveillance, survivorship, and hospice care. Germline testing and ctDNA testing are both important considerations in these patients. An example of hospice testing would be patient who is admitted directly to hospice after a diagnosis of advanced pancreas cancer. Saliva-based germline testing prior to death in such a patient has major ramifications for family members whether the test is positive for a mutation or not. cfDNA can be used in surveillance for recurrence.
Many oncology practices and hospital cancer programs are underprepared to take advantage of these important trends in cancer care.
HIGHGATE Genetics provides a practical pathway for oncology practices or practitioners and hospital systems to overcome the barriers to incorporating genetics into oncology practice. This pathway includes genetics education, program design, and business planning.
