Trends in genetic testing for breast and ovarian cancer: Undertesting and racial/ethnic disparities persist

Researchers have tracked the evolution of genetic germline testing in women with breast or ovarian cancer in recent years and reported the results in the Journal of Clinical Oncology.

Study author Allison W. Kurian, MD, of Stanford (Calif.) University, describes the group’s findings (https://bit.ly/31RaSGR) to guest host Alan Lyss, MD, subprincipal investigator emeritus for Heartland Cancer Research NCORP, in this episode.

Study rationale and methods

• Dr. Kurian said that an inflection point for breast cancer genetics was in 2013 when the U.S. Supreme Court ruled that gene patenting was not allowed for the purposes of genetic testing. As a result, the cost of testing BRCA1/2 genes fell, and testing became much more accessible.
• With their study, Dr. Kurian and colleagues aimed to look at trends following the increase in accessibility.
• The researchers used Surveillance, Epidemiology, and End Results Program (SEER) records of women aged 20 years and older who were diagnosed with breast or ovarian cancer from 2013 to 2017 in California or Georgia. The team linked these data to results of clinical germline testing through 2019.
• Dr. Kurian explained that the SEER data are comprehensive enough that all cancer cases in California and Georgia were likely included, the states provide a large catchment area of about 50 million people, and the states have different kinds of racial/ethnic diversity and urban/rural distribution.
• The researchers used the data to assess testing trends as well as rates of variants of uncertain significance (VUS) and pathogenic variants (PVs).

Results by hypothesis

Hypothesis 1: Multigene panels will entirely replace testing for BRCA1/2 only.

• This hypothesis was essentially correct. Testing of only two genes was almost totally replaced by testing many more genes.
• The number of genes tested for breast cancer increased annually by 28% over the study period.

Hypothesis 2: Underutilization of testing patients with ovarian cancer will improve over time.

• It is standard of care to recommend genetic testing for all ovarian cancer patients.
• Based on 2013-2014 data, only one-third of women were tested.
• As tests became more accessible in subsequent years, the hope was that more women would be tested.
• Unfortunately, there was very little improvement in testing rates over the study period.

Hypothesis 3: More patients will be tested at lower levels of pretest risk for PVs.

• In patients aged older than 60 years, testing rates increased for breast cancer (from 11% to 15%) and ovarian cancer (from 25% to 31%).
• Patients aged younger than 45 years had lower testing rates over time, however.
• Dr. Kurian noted that about 33% of ovarian cancer patients undergo genetic testing, but the goal is 100%.
• It is unclear if the goal should be 100% for breast cancer, Dr. Kurian said.

Hypothesis 4: Sociodemographic difference in testing trends would not be seen.

• There was not much of a gap observed with breast cancer patients. For example, among patients with breast cancer, approximately 31% of those who had genetic testing were uninsured, 31% had Medicaid, and 26% had private insurance or Medicare.
• There is more of an equity issue with ovarian cancer. About 28% of those who had genetic testing were uninsured, 27% had Medicaid, and 39% had private insurance or Medicare.
• Dr. Kurian said disparities in ovarian cancer persist in patients who are uninsured and those in certain racial/ethnic groups, including African Americans. These patients are less likely to get genetic testing.

Hypothesis 5: Detection of PVs and VUS will increase.

• The detection of VUS increased at a higher rate in comparison with PVs when more genes were being tested. This is likely because of the fact that, for every PV you find, you will find many more VUS, Dr. Kurian said.

Hypothesis 6: Racial or ethnic disparities in rates of VUS will diminish over time.

• Disparities actually increased over the study period as more genes were tested.
• Some studies have suggested that VUS results lead to unnecessary prophylactic surgery, Dr. Kurian said. She added that the decision to undergo prophylactic surgery should not be based on a VUS because “the great majority of VUS turn out to be nothing.”

Additional findings and implications for practice

• The study revealed that most PVs were in 20 genes associated with breast or ovarian cancer.
• Dr. Kurian and colleagues concluded that the way to improve testing is to focus on thos