Germline Testing of Patients With Non-small Cell Lung Cancers Demonstrating Incidentally Uncovered BRCA2 Apparent
1Winston-Salem, 27104 NC, USA.
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.
Insights
Next-generation sequencing (NGS) for non-small cell lung cancer (NSCLC) may reveal incidental BRCA2 pathogenic germline variants (PGVs). This necessitates careful consideration of germline testing, patient counseling, and potential therapeutic and surveillance implications.
Area of Science:
- Oncology
- Genetics
- Molecular Diagnostics
Background:
- Next-generation sequencing (NGS) is standard for identifying actionable genetic alterations in non-small cell lung cancer (NSCLC).
- Tumor NGS can incidentally detect apparent pathogenic germline variants (PGVs), most commonly in the BRCA2 gene.
- The implications of incidental PGVs, particularly BRCA2, in NSCLC patients require careful evaluation.
Purpose of the Study:
- To discuss the evidence for and against germline testing in NSCLC patients with incidental BRCA2 PGVs.
- To highlight the importance of pre-test counseling regarding the possibility of incidental PGVs.
- To review the uncertainties surrounding the identification and management of incidental BRCA2 PGVs.
Main Methods:
- Review of current evidence regarding germline testing in NSCLC.
- Discussion of clinical management strategies for patients with incidental BRCA2 PGVs.
- Case illustration to emphasize patient communication.
Main Results:
- Incidental BRCA2 PGVs in NSCLC can have implications for targeted therapies and cancer surveillance for patients and families.
- Germline testing confirmation of a BRCA2 PGV may guide treatment decisions after standard NSCLC therapies are exhausted.
- Patient understanding and informed consent are crucial due to potential findings and uncertainties.
Conclusions:
- Germline testing for incidental BRCA2 PGVs in NSCLC patients requires a balanced consideration of potential benefits and uncertainties.
- Clear communication with patients about the possibility of incidental findings before tumor NGS is essential.
- Further research is needed to clarify the management and clinical utility of incidental PGVs in NSCLC.
