Germline Testing of Patients With Non-small Cell Lung Cancers Demonstrating Incidentally Uncovered BRCA2 Apparent Pathogenic Germline Variants

Abstract

Tumor next generation sequencing (NGS) is used to interrogate nearly every non-small cell lung cancer (NSCLC) for the purpose of identifying actionable genetic alterations. Occasionally, tumor NGS also uncovers "incidental" apparent pathogenic germline variants (PGVs), with BRCA2 being among the most common of those. If germline testing confirms a BRCA2 PGV in a patient with NSCLC, therapies targeting that BRCA2 PGV might be considered, if the patient has exhausted standard NSCLC therapeutic options. Surveillance and preventive therapies for BRCA2-related cancers would be recommended or considered for that patient, as well as for family members found to carry that same BRCA2 PGV. Here, I offer my perspective related to the evidence supporting and against germline testing in patients with NSCLCs that show incidental BRCA2 apparent PGVs. I use an example to underscore how important it is to explain to patients, before tumor NGS, the possibility of uncovering an incidental PGV. I also review the myriad uncertainties related to identifying a BRCA2 PGV, when the sole indication for germline testing was the uncovering of the incidental BRCA2 apparent PGV.

Keywords: BRCA2-assiciated risk; probable incident PGV.