Summary
New data showed that a rural model for the screening and prevention of at-risk patients for hereditary breast and ovarian cancer detects pathogenic mutations in unaffected patients prior to diagnosis, according to a presentation from the ASCO 2020 Annual Meeting (Abstract 1575).
“Genetic testing for at-risk, non-cancer patients continues to increase,” said study author Charles Hendrix Shelton, MD, in radiation oncology at Vidant Health. “Currently, we test all affected patients for hereditary breast and ovarian cancer prospectively. And we wanted to extend this to include risk assessment in unaffected patients at risk within our population.”
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Original Article
A Novel Testing & Prevention Model for Hereditary Ovarian & Breast Cancer
Oncology Times
By Catlin Nalley
New data showed that a rural model for the screening and prevention of at-risk patients for hereditary breast and ovarian cancer detects pathogenic mutations in unaffected patients prior to diagnosis, according to a presentation from the ASCO 2020 Annual Meeting (Abstract 1575).
“Genetic testing for at-risk, non-cancer patients continues to increase,” said study author Charles Hendrix Shelton, MD, in radiation oncology at Vidant Health. “Currently, we test all affected patients for hereditary breast and ovarian cancer prospectively. And we wanted to extend this to include risk assessment in unaffected patients at risk within our population.”
The research team hypothesized that rural areas could have higher than expected familial risks of breast and ovarian cancers due to demographic and social factors. Therefore, they created a model to assess their population for familial cancer risk, provide counseling and testing, and based on outcomes offer risk-reduction strategies.
Study Design & Findings
A family history questionnaire was designed to assess the risk of hereditary breast and ovarian cancer based on current NCCN guidelines. This tool was used at key intake points among the unaffected population to evaluate their eligibility for genetic testing, as well as risk stratification.
The questionnaire, Shelton noted, “was offered first to women presenting for routine screening mammography and then second in the GYN clinics to capture the younger patients who weren't candidates for screening mammography.”
Patients who met hereditary breast and ovarian cancer screening were sent a letter and two phone calls to schedule genetic counseling. The key study endpoints included number of screened patients (affected and unaffected by cancer), number meeting criteria for germline testing, number of seen and tested, number of positives and negatives, and the actions taken based on those results.
In the first 8 months of the program, 3,133 women were screened. “Surprisingly, 22.5 percent of all patients that were screened with our questionnaire met criteria for testing, which was much higher than we thought it was going to be,” Shelton reported. “Of course, some of these patients do have existing breast cancer.”
Six percent of women screened at the time of mammogram had personal histories of breast or ovarian cancer (affected patients), according to the study authors. Ninety-four percent of screened patients were unaffected (N=2,950).
Multi-gene panel testing was done for all patients agreeable to testing. The median was a 19-gene panel (19-84 genes), according to Shelton.
“With a surprisingly large number of patients who met criteria (N=613), we've only been able to see about 210 patients who've completed counseling and of those 204 have been tested,” Shelton explained.
“So, about 25 percent of our unaffected patient populations still meet criteria,” he noted. “What we found was that germline mutations occur in 5 percent of our screened and tested unaffected patients. The screening mammogram population was used to analyze our rates of eligibility and testing rates as we had both controlled numerators and denominators to allow analysis.”
Some patients did not follow up to either letters or phones calls to agree to be tested. According to Shelton, they will be contacted on subsequent intake.
The researchers observed that, in the unaffected population, one in 590 patients screened for hereditary breast and ovarian cancer carry a known BRCA mutation. Shelton also noted that “one in 295 carry a non-BRCA or BRCA mutation together.”
“This model of screening works,” Shelton said. “It detects the unknown background germline risks for patients who have potential risk for cancer before they're diagnosed. Interestingly, the rate of positive mutations was almost exactly what it is in our existing breast cancer population, which is about 5-10 percent. This validates that the guidelines are effective at determining who needs to be screened.”
Shelton emphasized the importance of discovering a pathogenic mutation before cancer, which allows for targeted screening and risk-reduction strategies. The researchers plan to use more expanded panel testing as newer mutations become linked to hereditary breast and ovarian cancer.
Given the high population carrier rate (1 in 295) observed by the researchers, Shelton noted the potential value of a mass screening program. “One could argue that a mass screening tool, which would include, for example, Lynch syndrome, BRCA, and common non-BRCA mutations, might be a more efficient way to test patients,” he concluded.
Catlin Nalley is a contributing writer.