Risk perception and surveillance uptake in individuals at increased risk for pancreatic ductal adenocarcinoma.

BACKGROUND: Surveillance for pancreatic ductal adenocarcinoma (PDAC) is recommended for high-risk individuals with genetic variants in PDAC-associated genes and/or family history. Surveillance uptake and adherence may depend on the perception of PDAC risk and cancer worry. We aimed to determine PDAC risk perception in at-risk individuals and assess factors associated with PDAC surveillance uptake. METHODS: At-risk individuals identified from a prospective academic registry were sent a survey electronically. PDAC risk perception, cancer worry and surveillance uptake were surveyed. Factors associated with increased risk perception and surveillance were assessed. Five-year PDAC risk was calculated using the PancPRO risk assessment model, and correlation with subjective risk assessment was assessed. RESULTS: The overall survey response rate was 34% (279/816). The median perceived PDAC risk was twofold (IQR 1-4) above respondents' estimates of general population risk. Factors significantly associated with higher perceived PDAC risk included non-Hispanic white race, post-graduate education level, PDAC-affected first-degree relative, genetic variants and lack of personal cancer history. Cancer worry had a very weak correlation across PDAC risk estimates (r=0.16). No correlation between perceived PDAC risk and 5-year calculated PDAC risk was found. Older age, having a first-degree relative with PDAC, meeting with a medical provider about PDAC cancer risk and awareness of surveillance modalities were significant predictors of undergoing PDAC surveillance. CONCLUSIONS: Individuals at risk for PDAC do not report risk perception that correlates with calculated risk. This presents an opportunity for counselling of at-risk patients to individualise management and improve surveillance uptake for eligible individuals.

Germline CDH1 Variants and Lifetime Cancer Risk.

Importance: Approximately 1% to 3% of gastric cancers and 5% of lobular breast cancers are hereditary. Loss of function CDH1 gene variants are the most common gene variants associated with hereditary diffuse gastric cancer and lobular breast cancer. Previously, the lifetime risk of gastric cancer was estimated to be approximately 25% to 83% and for breast cancer it was estimated to be approximately 39% to 55% in individuals with loss of function CDH1 gene variants. Objective: To describe gastric and breast cancer risk estimates for individuals with CDH1 variants. Design, Setting, and Participants: Multicenter, retrospective cohort and modeling study of 213 families from North America with a CDH1 pathogenic or likely pathogenic (P/LP) variant in 1 or more family members conducted between January 2021 and August 2022. Main Outcomes and Measures: Hazard ratios (HRs), defined as risk in variant carriers relative to noncarriers, were estimated for each cancer type and used to calculate cumulative risks and risks per decade of life up to age 80 years. Results: A total of 7323 individuals from 213 families were studied, including 883 with a CDH1 P/LP variant (median proband age, 53 years [IQR, 42-62]; 4% Asian; 4% Hispanic; 85% non-Hispanic White; 50% female). In individuals with a CDH1 P/LP variant, the prevalence of gastric cancer was 13.9% (123/883) and the prevalence of breast cancer among female carriers was 26.3% (144/547). The estimated HR for advanced gastric cancer was 33.5 (95% CI, 9.8-112) at age 30 years and 3.5 (95% CI, 0.4-30.3) at age 70 years. The lifetime cumulative risk of advanced gastric cancer in male and female carriers was 10.3% (95% CI, 6%-23.6%) and 6.5% (95% CI, 3.8%-15.1%), respectively. Gastric cancer risk estimates based on family history indicated that a carrier with 3 affected first-degree relatives had a penetrance of approximately 38% (95% CI, 25%-64%). The HR for breast cancer among female carriers was 5.7 (95% CI, 2.5-13.2) at age 30 years and 3.9 (95% CI, 1.1-13.7) at age 70 years. The lifetime cumulative risk of breast cancer among female carriers was 36.8% (95% CI, 25.7%-62.9%). Conclusions and Relevance: Among families from North America with germline CDH1 P/LP variants, the cumulative risk of gastric cancer was 7% to 10%, which was lower than previously described, and the cumulative risk of breast cancer among female carriers was 37%, which was similar to prior estimates. These findings inform current management of individuals with germline CDH1 variants.

Outcomes of Universal Point-of-Care Genetic Testing in Diverse Patients With Pancreatic Ductal Adenocarcinoma.

PURPOSE: Guidelines recommend all patients with pancreatic ductal adenocarcinoma (PDAC) undergo germline genetic testing (GT). Rates of recommendation and completion of GT among diverse patients with PDAC are not known. The aim was to determine rates of recommendation and completion of point-of-care GT in diverse patients with PDAC. METHODS: A retrospective review of patients with PDAC seen at an academic center between April 2019 and December 2020 was performed. Recommendation, completion and results of point-of-care GT, and demographic and clinical factors were recorded. Univariate and multivariate analyses of GT were performed using the chi-square test and logistic regression. RESULTS: In total, 579 patients with PDAC were included. The median age at diagnosis was 67 years; 52% were male; 63% were non-Hispanic White (NHW) patients, and 20% were African American (AA) patients. GT was performed in 216 (37%) patients. Of those tested, 47 (22%) had a pathogenic/likely pathogenic variant identified of which 25 (12%) were in PDAC-associated genes. On multivariate analysis, age, NHW race, personal and family cancer history, medical oncology visit, and number of visits were independent predictors of GT completion. AA patients had significantly lower rates of recommendation and completion of GT compared with NHW patients. CONCLUSION: Point-of-care GT in patients with PDAC is unacceptably low, especially among AA patients. Testing disparity might be due to lack of provider recommendation more than patient uptake. Lack of testing leads to missed opportunities for potential targeted therapies, improved outcomes, and identification of at-risk family members who could potentially benefit from surveillance.