Germline Genetic Testing After Cancer Diagnosis

Abstract

Importance: Germline genetic testing is recommended by practice guidelines for patients diagnosed with cancer to enable genetically targeted treatment and identify relatives who may benefit from personalized cancer screening and prevention.

Objective: To describe the prevalence of germline genetic testing among patients diagnosed with cancer in California and Georgia between 2013 and 2019.

Design, setting, and participants: Observational study including patients aged 20 years or older who had been diagnosed with any type of cancer between January 1, 2013, and March 31, 2019, that was reported to statewide Surveillance, Epidemiology, and End Results registries in California and Georgia. These patients were linked to genetic testing results from 4 laboratories that performed most germline testing for California and Georgia.

Main outcomes and measures: The primary outcome was germline genetic testing within 2 years of a cancer diagnosis. Testing trends were analyzed with logistic regression modeling. The results of sequencing each gene, including variants associated with increased cancer risk (pathogenic results) and variants whose cancer risk association was unknown (uncertain results), were evaluated. The genes were categorized according to their primary cancer association, including breast or ovarian, gastrointestinal, and other, and whether practice guidelines recommended germline testing.

Results: Among 1 369 602 patients diagnosed with cancer between 2013 and 2019 in California and Georgia, 93 052 (6.8%) underwent germline testing through March 31, 2021. The proportion of patients tested varied by cancer type: male breast (50%), ovarian (38.6%), female breast (26%), multiple (7.5%), endometrial (6.4%), pancreatic (5.6%), colorectal (5.6%), prostate (1.1%), and lung (0.3%). In a logistic regression model, compared with the 31% (95% CI, 30%-31%) of non-Hispanic White patients with male breast cancer, female breast cancer, or ovarian cancer who underwent testing, patients of other races and ethnicities underwent testing less often: 22% (95% CI, 21%-22%) of Asian patients, 25% (95% CI, 24%-25%) of Black patients, and 23% (95% CI, 23%-23%) of Hispanic patients (P < .001 using the χ2 test). Of all pathogenic results, 67.5% to 94.9% of variants were identified in genes for which practice guidelines recommend testing and 68.3% to 83.8% of variants were identified in genes associated with the diagnosed cancer type.

Conclusions and relevance: Among patients diagnosed with cancer in California and Georgia between 2013 and 2019, only 6.8% underwent germline genetic testing. Compared with non-Hispanic White patients, rates of testing were lower among Asian, Black, and Hispanic patients.

Figure 1.. Modeled Probability of Genetic Testing Over Time in the Most Common Cancer Types Diagnosed From 2013 to 2019

The probabilities were predicted from a logistic regression model that included variables for age, cancer type, diagnosis year (2013-2019), and a diagnosis year × cancer type interaction, averaging across a constant age distribution for all years and cancer types. The shading around the curves represents 95% CIs.

Figure 2.. Modeled Probability of Genetic Testing Over Time Across Racial and Ethnic Groups

The probabilities were predicted from a logistic regression model that included age, cancer type, diagnosis year (2013-2019), an indicator for the 3 cancer types (male breast, female breast, and ovarian) with the highest testing rates that had testing guidelines throughout the study period, and 3 interactions: (1) cancer type and age, (2) racial and ethnic group and year, and (3) the 3 cancer types (male breast, female breast, and ovarian) with the highest testing rates and racial and ethnic group. The estimates were averaged across constant age and cancer type distributions within each of (1) other cancer types (excluded male breast, female breast, and ovarian) and (2) only male breast, female breast, and ovarian cancer types. The racial and ethnic categories were mutually exclusive. The shading around the curves represents 95% CIs. ^aIncludes all cancer types not included in panel B. ^bIncludes patients with Surveillance, Epidemiology, and End Results race1 variable coded as Native American, unknown, and Other.

Figure 3.. Distribution of Genes for Patients With Pathogenic Results

The results are grouped by associated cancer types or hereditary syndromes and by practice guideline indications for testing across selected cancer types (additional details appear in eTable 1 in Supplement 1).