Genomics Is a ‘Truly Powerful Tool’ for Changing Lung Cancer Outcomes

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Given its potential to impact health, physicians should not hesitate to refer families with a strong history of cancer for genetic counseling and testing.

The past decades have produced huge advances in how physicians understand the genomics of lung cancer, explains Geoffrey Oxnard, MD. “Lung cancer in never-smokers is itself a common cancer, yet it has a distinct genetic fingerprint that makes it more amenable to targeted therapies and less amenable to immunotherapies,” he says. “In contrast, the inherited genetics that underpins lung cancer risk is poorly understood, especially in individuals who never smoked. In our research, we studied a rare familial syndrome to begin to characterize how inherited genetics may lead to lung cancer risk.”

The study’s findings are published in the Journal of Clinical Oncology.

Mutation Associated With Treat Resistance & Poorer Outcomes

According to Dr. Oxnard and colleagues, the primary hypothesis of this study was that researchers could use widespread genomic analysis of diagnosed lung cancer to identify families carrying rare germline mutations in EGFR and thus could describe a rare familial lung cancer syndrome. “We launched a remote participation study, offering consent and counseling and genetic testing, to identify and study these lung cancer patients and their relatives,” Dr. Oxnard says.

They studied the mutation EGFR T790M, which has been associated with treatment resistance and poorer outcomes, Dr. Oxnard points out. “Here we find that this mutation, when detected at diagnosis, indicates a high risk of an inherited mutation that carries familial lung cancer risk.” Fortunately, with newer treatments Dr. Oxnard reports that “patients with lung cancer with germline EGFR T790M have the potential to have favorable outcomes when receiving the appropriate targeted therapy,” he says. “It is important that we connect that a germline variant not only has risk implications, but it also has treatment implications. By identifying families at risk of lung cancers driven by EGFR, we empower them with knowledge about a potential future lung cancer diagnosis and how to treat it. (Figure).”

Cancer Genetic Testing Can Empower Patients

Cancer genomics, he adds, is a “truly powerful tool” for changing outcomes in this type of lung cancer. “Through genetic testing, we have the power to identify a wide range of treatments and even gain insight into the germline risk genes that could have led to a lung cancer diagnosis,” he notes. “In this way, cancer genetic testing empowers patients to understand and gain agency in their own cancer journey.”

Dr. Oxnard and colleagues agree that the high prevalence of EGFR-driver lung adenocarcinomas and lung nodules in germline carriers bolsters efforts to identify affected patients and family members for investigation of CT-based screening. While familial lung cancer is rare, it is a true phenomenon, Dr. Oxnard explains. “For families with a strong cancer history, physicians should not hesitate to refer them for genetic counseling and testing as it could greatly impact their future,” he says.

“We are still trying to fully describe the role of CT screening in individuals with inherited lung cancer risk,” he says. “The benefit is clear, based on smoking history, but that is merely one simplification of our broader understanding of lung cancer risk. Optimal CT screening and subsequent nodule management for families with germline EGFR mutations remains an area of active investigation.”

Dr. Oxnard adds that efforts are underway to expand upon this study’s data, including correlative studies with remote participation, to explore the clinical characteristics and natural history of EGFR germline risk variants (T790M and others). This, he says, may lead to the application of a screening component in patients identified as carriers of EGFR germline variants that increase the risk of developing lung cancer.