journal contribution posted on 2023-03-31, 23:13 authored by Brittany L. Bychkovsky, Tianyu Li, Jilliane Sotelo, Nabihah Tayob, Joanna Mercado, Israel Gomy, Anu Chittenden, Sarah Kane, Samantha Stokes, Melissa E. Hughes, Ji Seok Kim, Renato Umeton, Mark M. Awad, Panagiotis A. Konstantinopoulos, Matthew B. Yurgelun, Brian M. Wolpin, Mary-Ellen Taplin, Randall E. Newmark, Bruce E. Johnson, Neal I. Lindeman, Laura E. MacConaill, Judy E. Garber, Nancy U. Lin
Supplementary Table from Identification and Management of Pathogenic Variants in BRCA1, BRCA2, and PALB2 in a Tumor-Only Genomic Testing Program
Breast Cancer Research Foundation (BCRF)
The DiNovi Family Profile Fund at Dana-Farber
The Legere Family Fund for Profile
Fashion Footwear Association of New York (FFANY)
de Beaumont Foundation
NCI Specialized Program of Research Excellence
National Comprehensive Cancer Network (NCCN)
ARTICLE ABSTRACTTumor-only genomic testing can uncover somatic and germline pathogenic variants [pathogenic/likely pathogenic (P/LP)] in cancer predisposition genes. We describe the prevalence of P/LPs in BRCA1/2 and PALB2 (B1B2P2) across malignancies and the frequency of clinical germline testing (CGT) in patients with P/LPs in B1B2P2 identified on tumor-only testing.
Among 7,575 patients with cancer tested between 2016 and 2018 with the OncoPanel tumor-only sequencing assay, we characterized P/LP frequencies by tumor type, receipt of CGT prior to or within 12 months after OncoPanel, and factors associated with CGT.
272 (3.6%) patients had OncoPanel-detected P/LPs in B1B2P2: 37.5% of P/LPs were in BRCA-related cancers; the remainder were in non-BRCA tumors. P/LPs were detected in ≥5% of breast, pancreatic, prostate, ovarian, nonmelanoma skin, endometrial, small cell lung, and colorectal cancers. 37.9% of patients with P/LPs received CGT prior to OncoPanel; an additional 10.7% underwent CGT within 12 months of OncoPanel. Among 132 with CGT, 88.6% had ≥1 clinical factor for CGT compared with 47.1% who did not undergo CGT. Patients with BRCA tumors were more likely to have CGT compared with those without (81.4% vs. 29.0%, P < 0.0001). Among patients with CGT, 70.5% (93/132) of P/LPs were germline.
Tumor-only genomic testing identified P/LPs in B1B2P2 in 3.6% of patients. 52.9% of patients with tumor-detected P/LPs and without CGT did not meet personal or family history criteria for CGT. In addition, some patients with tumor-detected P/LPs were not referred for CGT, especially those with non-BRCA tumors. Given implications for treatment selection and familial cancer risk, processes to reliably trigger CGT from tumor-genomic findings are needed.