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TOPLINE:

Germline genetic testing for pancreatic ductal adenocarcinoma (PDAC) remains incompletely implemented, with only 66% of patients offered testing and 69% completing it. Black patients, uninsured individuals, and those treated in community settings face significantly lower odds of being offered and completing testing, while only 62% of mutation-positive patients report cascade testing among first-degree relatives.

METHODOLOGY:

• Approximately 10%-15% of patients with PDAC harbor pathogenic germline genetic alterations, most frequently in genes involved in homologous recombination repair (HRR) including BRCA1, BRCA2, PALB2, and ATM, with direct therapeutic implications for platinum-based chemotherapy and PARP inhibition.
• Current National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines recommend germline testing for all patients with PDAC regardless of family history, based on the relatively high prevalence of germline genetic alterations even in patients without documented prior family history of cancer. Existing data show that real-world uptake of germline testing among all patients with cancer including PDAC remains low or suboptimal, with barriers to guideline-recommended universal germline testing remaining poorly understood.
• Researchers conducted a cross-sectional electronic survey in collaboration with the Pancreatic Cancer Action Network (PanCAN), distributing surveys to 22,141 registry participants and community members in the US between October and December 2024.
• A total of 1046 respondents with pancreatic cancer were included in the analysis after excluding those with pancreatic neuroendocrine tumors.
• Primary outcomes included whether respondents were offered and whether they completed germline genetic testing following PDAC diagnosis.
• Secondary outcomes assessed genetic counseling receipt, financial burden, mutation results, and cascade testing among first-degree relatives.

TAKEAWAY:

• Black patients had 47% decreased odds of being offered germline genetic testing compared with White patients (odds ratio [OR], 0.53; P = .04), and 58% decreased odds of completing testing (OR, 0.42; P = .01).
• Uninsured patients had 83% lower odds of being offered testing compared with Medicare beneficiaries (OR, 0.17; P < .01) and 89% lower odds of completion (OR, 0.11; P < .01).
• Patients treated in community practices had significantly lower odds of being offered testing than those at academic/teaching hospitals (OR, 0.63; P < .01) and lower odds of completing testing (OR, 0.60; P < .01).
• Among tested participants, 23.2% had a pathogenic germline variant, most commonly BRCA2 (32.7%), ATM (15.2%), and BRCA1 (9.7%), and those who received genetic counseling were more likely to have cascade testing of a first-degree relative completed vs those who did not (67.7% vs 38.2%; P < .01).

IN PRACTICE:

“Universal germline genetic testing in PDAC remains incompletely implemented, with persistent inequities. Lack of discussion or offer of testing represents a key missed opportunity, underscoring the need for targeted interventions and expanded access,” the authors of the study wrote.

SOURCE:

This study was led by Udhayvir S. Grewal, MD, Winship Cancer Institute of Emory University in Atlanta. It was published online in Cancer.

LIMITATIONS:

The study cohort was drawn from individuals engaged with an advocacy organization, which may serve as a surrogate for higher health literacy, stronger disease awareness, and greater engagement with cancer-related resources, limiting generalizability. The survey was administered online and only in English, restricting participation to those with reliable internet access, basic technological proficiency, and English language fluency. The analysis is limited by recall bias that may directly affect the accuracy of data reported by respondents. The reported positivity rate for germline genetic alterations likely includes both clinically actionable pathogenic variants and lower-penetrance or secondary findings, which may explain the higher rate of 23.2% than prior reports of 10%-15%. The survey did not capture detailed information regarding the type of provider ordering genetic testing or whether testing occurred via point-of-care vs referral pathways.

DISCLOSURES:

Timothy J. Brown disclosed receiving consulting fees from Astellas Pharma, Daiichi Sankyo, and Incyte. Chandrikha Chandrasekharan reported receiving consulting fees from Adcendo and Exelixis Inc. Seth J. Concors disclosed receiving consulting fees from RYZ and fees for other professional activities from Curio Science. Grewal reported receiving consulting fees from Boehringer Ingelheim and fees for other professional activities from Exelixis. The remaining authors indicated no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.