Gene panel testing for breast cancer reveals differential effect of prior BRCA1/2 probability
Authors
Evans, D Gareth Rvan Veen, E M
Woodward, E R
Harkness, E F
Ellingford, J M
Bowers, N L
Wallace, A J
Howell, Sacha J
Howell, Anthony
Lalloo, F
Newman, W G
Smith Miriam J
Affiliation
NW Genomic Laboratory Hub, Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, ManchesterIssue Date
2021
Metadata
Show full item recordAbstract
Whilst panel testing of an extended group of genes including BRCA1/2 is commonplace, these studies have not been subdivided by histiotype or by a priori BRCA1/2 probability. Patients with a breast cancer diagnosis undergoing extended panel testing were assessed for frequency of actionable variants in breast cancer genes other than BRCA1/2 by histiotype and Manchester score (MS) to reflect a priori BRCA1/2 likelihood. Rates were adjusted by prior testing for BRCA1/2 in an extended series. 95/1398 (6.3%) who underwent panel testing were found to be positive for actionable non-BRCA1/2 breast/ovarian cancer genes (ATM, BARD1, CDH1, CHEK2, PALB2, PTEN, RAD51C, RAD51D, TP53). As expected, PALB2, CHEK2 and ATM were predominant with 80-(5.3%). The highest rate occurred in Grade-3 ER+/HER2- breast cancers-(9.6%). Rates of non-BRCA actionable genes was fairly constant over all likelihoods of BRCA1/2 but adjusted rates were three times higher with MS < 9 (BRCA1/2 = 1.5%, other = 4.7%), but was only 1.6% compared to 79.3% with MS ≥ 40. Although rates of detection of non-BRCA actionable genes are relatively constant across BRCA1/2 likelihoods this disguises an overall adjusted low frequency in high-likelihood families which have been heavily pre-tested for BRCA1/2. Any loss of detection sensitivity for BRCA1/2 actionable variants in breast cancer panels should lead to bespoke BRCA1/2 testing being conducted first.Citation
Evans DG, van Veen EM, Woodward ER, Harkness EF, Ellingford JM, Bowers NL, et al. Gene Panel Testing for Breast Cancer Reveals Differential Effect of Prior BRCA1/2 Probability. Cancers. 2021 Aug 18;13(16):4154.Journal
CancersDOI
10.3390/cancers13164154PubMed ID
34439310Additional Links
https://dx.doi.org/10.3390/cancers13164154Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.3390/cancers13164154