Estimated prevalence of pathogenic variants in patients with breast, colon, and/or endometrial cancer who do not meet guidelines for genetic testing.
Year: 2025
Type: conference-abstract
Abstract: 10577 Background: Patients with cancer who carry pathogenic variants (PVs) in hereditary cancer genes often have improved outcomes when their treatment is guided by their germline genetics. Identifying germline PVs also allows cascade testing of family members to pursue cancer prevention interventions. Guidelines recommend genetic testing for patients with female breast (BC), colorectal (CRC), or endometrial cancer (EC) who meet specific criteria, including early age at diagnosis and/or family history (FH). However, many patients with cancer who do not meet these guidelines may unknowingly carry PVs and may, therefore, receive suboptimal care. Methods: Multivariable logistic regression models were constructed to analyze trends in the prevalence of PVs based on age and FH in a consecutive cohort of patients referred for hereditary cancer testing (MyRisk, Myriad Genetics). We report model-based prevalence estimates for patients without FH diagnosed with BC, CRC, or EC at various ages. Prevalence is summarized overall for 25-48 hereditary cancer genes and for genes most frequently implicated in each cancer type. Results: Estimates of prevalence of PVs among patients with BC and CRC decreased substantially with age of diagnosis (Table 1). For patients with BC/CRC (respectively) without FH, overall prevalence estimates were 13.0%/11.8% among those diagnosed at age 30, 6.9%/7.1% at age 50 and 2.5%/3.2% at age 80. Among BC patients, PVs were most frequently identified in the BRCA1, BRCA2, CHEK2, ATM, and PALB2 genes. Among CRC patients, PVs were most prevalent in the Lynch syndrome genes MLH1, MSH2, MSH6, PMS2 . Prevalence was not significantly associated with age at EC diagnosis. Women with no FH had overall prevalence estimates of 7.5% if diagnosed with EC at age 30, 7.3% at age 50 and 7.1% at age 80 (Table 1). PVs were most common in the aforementioned Lynch syndrome genes. Conclusions: These results support existing literature that a substantial fraction of patients who do not meet guidelines for genetic testing may carry PVs, including a high prevalence of PVs among EC patients without FH, regardless of age at diagnosis. Elimination of age-based restrictions on genetic testing could improve the survival of cancer patients and their family members. Estimated prevalence (%) according to age of diagnosis among patients with no family history of cancer. Age at dx 30 40 50 60 70 80 BC 13.0% 9.5% 6.9% 5.0% 3.5% 2.5% CRC 11.8% 9.2% 7.1% 5.5% 4.2% 3.2% EC 7.5% 7.4% 7.3% 7.2% 7.2% 7.1% BC a 12.3% 8.3% 5.6% 3.7% 2.4% 1.6% CRC b 7.3% 5.1% 3.5% 2.4% 1.7% 1.1% EC b 4.4% 4.3% 4.3% 4.2% 4.1% 4.1% BC=breast cancer; CRC=colorectal cancer; dx=diagnosis; EC=endometrial cancer. a BRCA1, BRCA2, CHEK2, ATM, or PALB2. b MLH1, MSH2, MSH6, or PMS2.
Source: Journal of Clinical Oncology
Authors: Ryan Bernhisel, Matthew Kucera, Edith Smith, Stephanie Rieder, Shelly Ann Cummings, Joan L. Walker, Elisha Hughes
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funder: Myriad Genetics
OpenAlex ID: W4410817753