Germline genetic testing use and results after a cancer diagnosis.
Authors: Kurian Allison W. , Abrahamse Paul , Furgal Allison Kate Cullen , Ward Kevin C , Hamilton Ann S. , Hodan Rachel , Liu Lihua , Berek Jonathan S. , Hoang Lily , Yussuf Amal , Susswein Lisa R. , Esplin Edward D. , Slavin Thomas Paul , Gomez Scarlett L. , Hofer Timothy , Katz Steven 
Published: June 2023

10500

Background: Germline genetic testing is increasingly essential for cancer prevention and treatment. There is a growing call for universal germline testing after a cancer diagnosis. In this evolving context, little is known about genetic testing use and results across cancer types at the population level. Methods: All patients aged ≥20 years, diagnosed with any cancer type and reported to statewide Surveillance Epidemiology and End Results (SEER) registries in Georgia and California from 2013-2019, were linked to 2013-2021 results from four laboratories providing nearly all germline testing in these regions. Testing use was evaluated in patients diagnosed with all cancer types reported by SEER. Pathogenic variant (PV) and variant of uncertain significance (VUS-only) results were evaluated across cancer types. Tested genes were grouped by major cancer associations and by clinical guidelines for testing and results management after a cancer diagnosis, as follows: breast/ovarian including BRCA1/2; gastrointestinal including the Lynch syndrome genes ( MLH1, MSH2, MSH6, PMS2, EPCAM); other hereditary cancer syndromes; and preliminary evidence genes with no clinical guidelines. Genetic testing trends were analyzed with logistic regression modeling. Results: Among 1,369,660 patients, 6.8% linked to genetic testing results. Genetic testing use was highest among patients with male breast cancer (50.0%), followed by ovarian cancer (38.6%), female breast cancer (26%), multiple primary cancers (7.5%), endometrial cancer (6.4%), pancreatic cancer (5.6%), colorectal cancer (5.6%), prostate cancer (1.1%) and lung cancer (0.3%). Genetic testing use increased over time, notably ten-fold for pancreatic cancer (2013 diagnoses, 1.2%; 2019 diagnoses, 18.6%). Most (67.5-89.6%) of identified PVs were in genes with clinical guidelines for testing and management, and had an established association with the patient's cancer type (breast/ovarian including BRCA1/2: 79.5% of PVs in patients with female breast cancer, 83.8% in patients with male breast cancer, 82.0% in patients with ovarian cancer; gastrointestinal including Lynch syndrome genes: 68.3% of PVs in patients with colorectal cancer, 71.8% in patients with endometrial cancer). Preliminary evidence genes comprised 5.1%-28.1% of PVs detected across cancer types. Compared to non-Hispanic Whites (NHW), patients from other racial/ethnic groups received less testing (Black, odds ratio (OR) 0.58, 95% confidence interval (CI) 0.55-0.63; Hispanic, OR 0.62, CI 0.58-0.66; Asian OR 0.71, CI 0.58-0.66) without improvement over time, and more VUS-only results (NHW, 24.9%; Black 39.0%; Asian, 40.0%), a difference which increased over time. Conclusions: At the population level, germline testing use is low across cancer types, falling short of guidelines. Racial/ethnic disparities in testing use and clarity of test results persisted over time. These gaps are priorities for intervention.