Characterization of variant reclassification and patient re-contact in a cancer genetics clinic.

Expanded genetic testing guidelines for hereditary cancers, increased utilization of large multigene panels, and improved methods for reclassifying variants have led to a greater need to understand how variant reclassification and patient re-contact are managed. This study aimed to describe the process of variant reclassification and subsequent patient re-contact at a comprehensive cancer genetic counseling service in a large metropolitan medical center with several statewide satellite locations. A retrospective chart review was performed to identify reclassified variants between 1/1/1997 and 12/1/2020. In total, 8.4% (211/2503) of variants were reclassified over the 24-year period, which includes multiple cases involving the same unique variant. Several variants underwent more than one reclassification, resulting in 232 total reclassifications among 194 individuals. Nearly all reclassifications were prompted by the laboratory (99.1%; 230/232) rather than the genetics clinic staff. Overall, 10.3% (24/232) of all reclassifications were upgrades, but only 9.1% (21/232) led to a change in management recommendations. The median time for variant reclassification was 1.7 years (interquartile range [IQR] = 0.8-3.2 years). There was no statistically significant difference in the time to reclassification for White patients (median = 1.6 years; IQR = 0.8-2.8 years) compared to non-White patients (median = 2.0 years; IQR = 0.9-3.7 years; Mann-Whitney U = 4,764.0, p = 0.066). Patient re-contact was attempted for 97.4% (226/232) of variants and was always performed by a genetic counselor, most often through a mailed letter (85.8%, 194/226). Specifically for reclassifications that led to a change in management recommendations, re-contact was always attempted, most often through combined telephone and mailed letter (95.2%; 20/21). Overall, the median time from reclassification to attempted patient re-contact was 13 days (range: 0-589 days). The characterization of this clinic's reclassification and re-contact procedures can serve as an example for other genetics clinics trying to incorporate re-contact into their workflow.

Racial and ethnic variation in multigene panel testing in a cohort of BRCA1/2-negative individuals who had genetic testing in a large urban comprehensive cancer center.

BACKGROUND: There is sparse clinical information on the racial and ethnic distribution of results of multigene panel testing among individuals at high risk for hereditary cancer. METHODS: We evaluated the results of multigene panel testing across eight clinical sites across the state of Michigan for individuals seen for genetic counseling from May 13, 2013 to October 31, 2019 at the Karmanos Cancer Institute's cancer genetics clinic. We estimated the prevalence of pathogenic variants and variants of uncertain significance (VUS) from genes other than BRCA1/2 among individuals of non-Hispanic White (NHW), Black or African American (AA), Ashkenazi Jewish (AJ), Arab, Hispanic, and other ancestry. RESULTS: The racial and ethnic distribution of 2419 individuals who had panel testing included 68.8% NHW, 22.1% AA, 2.3% Arab, 2.2% AJ, 1.0% Hispanic, and 3.6% other. Of these, 11.2% had pathogenic variants and 17.5% had VUS. After multivariable analyses, compared to NHW, AA were less likely to have pathogenic variants (OR 95% CI, 0.38, 0.24-0.59, p < 0.001). Both AA and Arabs were more likely to have VUS (OR 95% CI, 1.53, 1.18-1.98, p = 0.001 and OR 95% CI, 2.28, 1.17-4.43, p = 0.015, respectively). There were no significant differences for other groups. The most common pathogenic variants were CHEK2 (n = 65), MUTYH (n = 45), ATM (n = 28), and MSH2 (n = 22); the most common pathogenic variants by race and ethnicity were CHEK2 (NHW), MSH2 and MUTYH (AA), MSH2 (Arab), MSH6 and CHEK2 (AJ), and MLH1 (Hispanic); the most common pathogenic variants by primary cancer site were CHEK2 (breast), MSH2 (colon), BRIP1 and MUTYH (ovarian), and MSH2 and MSH6 (endometrial). CONCLUSIONS: Understanding the racial and ethnic distribution of pathogenic variants in multi-gene panels has the potential to lead to better identification of individuals at risk for hereditary cancer.