Dr. Alan P. Lyss
Investigators found racial and ethnic disparities in genetic testing as well as “persistent underuse” of testing in patients with ovarian cancer.
The team also discovered that most pathogenic variant (PV) results were in 20 genes associated with breast and/or ovarian cancer, and testing other genes largely revealed variants of uncertain significance (VUS).
Allison W. Kurian, MD, of Stanford (Calif.) University, and colleagues recounted these findings in the Journal of Clinical Oncology.
Because of improvements in sequencing technology, competition among commercial purveyors, and declining cost, genetic testing has been increasingly available to clinicians for patient management and cancer prevention (JAMA. 2015 Sep 8;314[10]:997-8). Although germline testing can guide therapy for several solid tumors, there is little research about how often and how well it is used in practice.
For their study, Dr. Kurian and colleagues used a SEER Genetic Testing Linkage Demonstration Project in a population-based assessment of testing for cancer risk. The investigators analyzed 7-year trends in testing among all women diagnosed with breast or ovarian cancer in Georgia or California from 2013 to 2017, reviewing testing patterns and result interpretation from 2012 to 2019.
Before analyzing the data, the investigators made the following hypotheses:
- Multigene panels (MGP) would entirely replace testing for BRCA1/2 only.
- Testing underutilization in patients with ovarian cancer would improve over time.
- More patients would be tested at lower levels of pretest risk for PVs.
- Sociodemographic differences in testing trends would not be observed.
- Detection of PVs and VUS would increase.
- Racial and ethnic disparities in rates of VUS would diminish.
Study conduct
The investigators examined genetic tests performed from 2012 through the beginning of 2019 at major commercial laboratories and linked that information with data in the SEER registries in Georgia and California on all breast and ovarian cancer patients diagnosed between 2013 and 2017. There were few criteria for exclusion.
Genetic testing results were categorized as identifying a PV or likely PV, VUS, or benign or likely benign mutation by American College of Medical Genetics criteria. When a patient had genetic testing on more than one occasion, the most recent test was used.
If a PV was identified, the types of PVs were grouped according to the level of evidence that supported pathogenicity into the following categories:
- BRCA1 or BRCA2 mutations.
- PVs in other genes designated by the National Comprehensive Cancer Network as associated with breast or ovarian cancer (e.g., ATM, BARD1, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, NBN, NF1, PALB2, MS2, PTEN, RAD51C, RAD51D, STK11, and TP53).
- PVs in other actionable genes (e.g., APC, BMPR1A, MEN1, MUTYH, NF2, RB1, RET, SDHAF2, SDHB, SDHC, SDHD, SMAD4, TSC1, TSC2, and VHL).
- Any other tested genes.
The investigators also tabulated instances in which genetic testing identified a VUS in any gene but no PV. If a VUS was identified originally and was reclassified more recently into the “PV/likely PV” or “benign/likely benign” categories, only the resolved categorization was recorded.
The authors evaluated clinical and sociodemographic correlates of testing trends for breast and ovarian cancer, assessing the relationship between race, age, and geographic site in receipt of any test or type of test.
Among laboratories, the investigators examined trends in the number of genes tested, associations with sociodemographic factors, categories of test results, and whether trends differed by race or ethnicity.
Findings, by hypothesis
Hypothesis #1: MGP will entirely replace testing for BRCA1/2 only.
About 25% of tested patients with breast cancer diagnosed in early 2013 received MGP, compared with more than 80% of those diagnosed in late 2017.
The trend for ovarian cancer was similar. About 40% of patients diagnosed in early 2013 received MGP, compared with more than 90% diagnosed in late 2017. These trends were similar in California and Georgia.
From 2012 to 2019, there was a consistent upward trend in gene number for patients with breast cancer (mean, 19) or ovarian cancer (mean, 21), from approximately 10 genes to 35 genes.
Hypothesis #2: Underutilization of testing in patients with ovarian cancer will improve.
Among the 187,535 patients with breast cancer and the 14,689 patients with ovarian cancer diagnosed in Georgia or California from 2013 through 2017, on average, testing rates increased 2% per year.
In all, 25.2% of breast cancer patients and 34.3% of ovarian cancer patients had genetic testing on one (87.3%) or more (12.7%) occasions.
Prior research suggested that, in 2013 and 2014, 31% of women with ovarian cancer had genetic testing (JAMA Oncol. 2018 Aug 1;4[8]:1066-72/ J Clin Oncol. 2019 May 20;37[15]:1305-15).
The investigators therefore concluded that underutilization of genetic testing in ovarian cancer did not improve substantially during the 7-year interval analyzed.
Hypothesis #3: More patients will be tested at lower levels of pretest risk.
These data were more difficult to abstract from the SEER database, but older patients were more likely to be tested in later years.
In patients older than 60 years of age (who accounted for more than 50% of both cancer cohorts), testing rates increased from 11.1% to 14.9% for breast cancer and 25.3% to 31.4% for ovarian cancer. By contrast, patients younger than 45 years of age were less than 15% of the sample and had lower testing rates over time.
There were no substantial changes in testing rates by other clinical variables. Therefore, in concert with the age-related testing trends, it is likely that women were tested for genetic mutations at increasingly lower levels of pretest risk.
Hypothesis #4: Sociodemographic differences in testing trends will not be observed.
Among patients with breast cancer, approximately 31% of those who had genetic testing were uninsured, 31% had Medicaid, and 26% had private insurance, Medicare, or other insurance.