Multi-gene panel testing for hereditary cancer susceptibility in a rural Familial Cancer Program

Abstract

This study explores our Familial Cancer Program's experience implementing multi-gene panel testing in a largely rural patient population. We conducted a retrospective review of patients undergoing panel testing between May 2011 and August 2015. Our goal was to evaluate factors that might be predictors of identifying variants (pathogenic or uncertain significance) and to assess clinical management changes due to testing. We utilized a structured family history tool to determine the significance of patient's family histories with respect to identification of genetic variants. A total of 227 patients underwent panel testing at our center and 67 patients (29.5 %) had variants identified, with 8 (3.5 %) having multiple variants. Overall, 44 patients (19.4 %) had a variant of uncertain significance (VUS) and 28 patients (12.3 %) had a pathogenic variant detected, with 10 (4.4 %) having pathogenic variants in highly penetrant genes. We found no statistical difference in patient familial and personal cancer history, age, rural status, Ashkenazi Jewish ancestry, insurance coverage and prior single-gene testing among those with pathogenic, VUS and negative panel testing results. There were no predictors of pathogenic variants on regression analysis. Panel testing changed cancer screening and management guidelines from that expected based on family history alone in 13.2 % of patients. Ultimately, cancer panel testing does yield critical information not identified by traditional single gene testing but maximal utility through a broad range of personal and family histories requires improved interpretation of variants.

Germline mutation landscape of Chinese patients with familial breast/ovarian cancer in a panel of 22 susceptibility genes

“…1 Clinical genetic testing for familial breast cancer (BC) has been transformed by the advent of massively parallel sequencing, which allows simultaneous screening of a large number of genes at a fraction of the cost on one gene sequencing previously. 2 However, there is a large portion of familial BC not associated with BRCA1/2 mutations. Familial BC often related to mutations of non-BRCA1/2 genes in homologous recombination (HR) pathway (ATM, CHEK2, BARD1, BRIP1, MRE11A, NBN and etc), by DNA damage response pathway (MSH2, MLH1, MSH6, PMS2 and etc) 3,4 and mismatch recognition pathway (MUTYH, EPCAM and etc).…”

Hereditary Cancer Genetic Panel Testing: A Review of the Literature

“…As a result, the data to provide accurate genetic assessments are limited, making it difficult to interpret risk and challenging to present risks to patients (Hiraki et al, 2014). A study conducted by a Familial Cancer Program in Vermont (n = 277) reviewed factors that were potential predictors of variants of uncertain significance and assessed changes in management tactics based on these factors (Hermel et al, 2016). Out of 227 patients, 67 patients had genetic variants and eight patients had multiple variants.…”

Genetic testing for hereditary breast and ovarian cancer and the USPSTF recommendations

“…Furthermore, panel testing is more cost effective compared to BRCA‐only testing . Panel testing has now become the norm in cancer genetics programs, although there are no specific guidelines regarding the optimal number of genes that should comprise a panel …”

“…10,11 Furthermore, panel testing is more cost effective compared to BRCA-only testing. 12,13 Panel testing has now become the norm in cancer genetics programs, [14][15][16] although there are no specific guidelines regarding the optimal number of genes that should comprise a panel. 6,7 Current indications for cancer genetic testing of affected individuals differ significantly from indications for testing of unaffected individuals.…”