Cargando…
Is Reflex Germline BRCA1/2 Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older?
SIMPLE SUMMARY: Approximately 15% of patients diagnosed with high-grade non-mucinous epithelial ovarian cancer (EOC) have a germline BRCA1/2 mutation, although all patients are often able to access germline testing. Importantly, the risk of familial ovarian cancer reduces with advancing age at diagn...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913244/ https://www.ncbi.nlm.nih.gov/pubmed/36765687 http://dx.doi.org/10.3390/cancers15030730 |
_version_ | 1784885377750794240 |
---|---|
author | Morgan, Robert D. Burghel, George J. Flaum, Nicola Bulman, Michael Smith, Philip Clamp, Andrew R. Hasan, Jurjees Mitchell, Claire L. Salih, Zena Woodward, Emma R. Lalloo, Fiona Crosbie, Emma J. Edmondson, Richard J. Schlecht, Helene Jayson, Gordon C. Evans, D. Gareth R. |
author_facet | Morgan, Robert D. Burghel, George J. Flaum, Nicola Bulman, Michael Smith, Philip Clamp, Andrew R. Hasan, Jurjees Mitchell, Claire L. Salih, Zena Woodward, Emma R. Lalloo, Fiona Crosbie, Emma J. Edmondson, Richard J. Schlecht, Helene Jayson, Gordon C. Evans, D. Gareth R. |
author_sort | Morgan, Robert D. |
collection | PubMed |
description | SIMPLE SUMMARY: Approximately 15% of patients diagnosed with high-grade non-mucinous epithelial ovarian cancer (EOC) have a germline BRCA1/2 mutation, although all patients are often able to access germline testing. Importantly, the risk of familial ovarian cancer reduces with advancing age at diagnosis. The aim of our study was to determine the prevalence of germline and somatic BRCA1/2 mutations in women diagnosed with non-mucinous high-grade EOC aged ≥80. We found that somatic BRCA1/2 mutations occurred nine times more frequently than germline BRCA1/2 mutations in women aged ≥80. The only germline BRCA1/2 mutation reported in a patient aged ≥80 was detected in both germline and tumour DNA. These data suggest that germline BRCA1/2 testing in women diagnosed with high-grade non-mucinous EOC aged ≥80 can be reserved for those with a detectable tumour BRCA1/2 mutation. ABSTRACT: Women diagnosed with non-mucinous high-grade epithelial ovarian cancer (EOC) in England are often reflex-tested for germline and tumour BRCA1/2 variants. The value of germline BRCA1/2 testing in women diagnosed aged ≥80 is questionable. We performed an observational study of all women diagnosed with non-mucinous high-grade EOC who underwent germline and tumour BRCA1/2 testing by the North West of England Genomic Laboratory Hub. A subgroup of women also underwent germline testing using a panel of homologous recombination repair (HRR) genes and/or tumour testing for homologous recombination deficiency (HRD) using Myriad’s myChoice® companion diagnostic. Seven-hundred-two patients successfully underwent both germline and tumour BRCA1/2 testing. Of these, 48 were diagnosed with non-mucinous high-grade EOC aged ≥80. In this age group, somatic BRCA1/2 pathogenic/likely pathogenic variants (PV/LPVs) were detected nine times more often than germline BRCA1/2 PV/LPVs. The only germline PV reported in a patient aged ≥80 was detected in germline and tumour DNA (BRCA2 c.4478_4481del). No patient aged ≥80 had a germline PV/LPVs in a non-BRCA1/2 HRR gene. Thirty-eight percent of patients aged ≥80 had a tumour positive for HRD. Our data suggest that tumour BRCA1/2 and HRD testing is adequate for patients diagnosed with non-mucinous high-grade EOC aged ≥80, with germline BRCA1/2 testing reserved for women with a tumour BRCA1/2 PV/LPVs. |
format | Online Article Text |
id | pubmed-9913244 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99132442023-02-11 Is Reflex Germline BRCA1/2 Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older? Morgan, Robert D. Burghel, George J. Flaum, Nicola Bulman, Michael Smith, Philip Clamp, Andrew R. Hasan, Jurjees Mitchell, Claire L. Salih, Zena Woodward, Emma R. Lalloo, Fiona Crosbie, Emma J. Edmondson, Richard J. Schlecht, Helene Jayson, Gordon C. Evans, D. Gareth R. Cancers (Basel) Article SIMPLE SUMMARY: Approximately 15% of patients diagnosed with high-grade non-mucinous epithelial ovarian cancer (EOC) have a germline BRCA1/2 mutation, although all patients are often able to access germline testing. Importantly, the risk of familial ovarian cancer reduces with advancing age at diagnosis. The aim of our study was to determine the prevalence of germline and somatic BRCA1/2 mutations in women diagnosed with non-mucinous high-grade EOC aged ≥80. We found that somatic BRCA1/2 mutations occurred nine times more frequently than germline BRCA1/2 mutations in women aged ≥80. The only germline BRCA1/2 mutation reported in a patient aged ≥80 was detected in both germline and tumour DNA. These data suggest that germline BRCA1/2 testing in women diagnosed with high-grade non-mucinous EOC aged ≥80 can be reserved for those with a detectable tumour BRCA1/2 mutation. ABSTRACT: Women diagnosed with non-mucinous high-grade epithelial ovarian cancer (EOC) in England are often reflex-tested for germline and tumour BRCA1/2 variants. The value of germline BRCA1/2 testing in women diagnosed aged ≥80 is questionable. We performed an observational study of all women diagnosed with non-mucinous high-grade EOC who underwent germline and tumour BRCA1/2 testing by the North West of England Genomic Laboratory Hub. A subgroup of women also underwent germline testing using a panel of homologous recombination repair (HRR) genes and/or tumour testing for homologous recombination deficiency (HRD) using Myriad’s myChoice® companion diagnostic. Seven-hundred-two patients successfully underwent both germline and tumour BRCA1/2 testing. Of these, 48 were diagnosed with non-mucinous high-grade EOC aged ≥80. In this age group, somatic BRCA1/2 pathogenic/likely pathogenic variants (PV/LPVs) were detected nine times more often than germline BRCA1/2 PV/LPVs. The only germline PV reported in a patient aged ≥80 was detected in germline and tumour DNA (BRCA2 c.4478_4481del). No patient aged ≥80 had a germline PV/LPVs in a non-BRCA1/2 HRR gene. Thirty-eight percent of patients aged ≥80 had a tumour positive for HRD. Our data suggest that tumour BRCA1/2 and HRD testing is adequate for patients diagnosed with non-mucinous high-grade EOC aged ≥80, with germline BRCA1/2 testing reserved for women with a tumour BRCA1/2 PV/LPVs. MDPI 2023-01-25 /pmc/articles/PMC9913244/ /pubmed/36765687 http://dx.doi.org/10.3390/cancers15030730 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Morgan, Robert D. Burghel, George J. Flaum, Nicola Bulman, Michael Smith, Philip Clamp, Andrew R. Hasan, Jurjees Mitchell, Claire L. Salih, Zena Woodward, Emma R. Lalloo, Fiona Crosbie, Emma J. Edmondson, Richard J. Schlecht, Helene Jayson, Gordon C. Evans, D. Gareth R. Is Reflex Germline BRCA1/2 Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older? |
title | Is Reflex Germline BRCA1/2 Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older? |
title_full | Is Reflex Germline BRCA1/2 Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older? |
title_fullStr | Is Reflex Germline BRCA1/2 Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older? |
title_full_unstemmed | Is Reflex Germline BRCA1/2 Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older? |
title_short | Is Reflex Germline BRCA1/2 Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older? |
title_sort | is reflex germline brca1/2 testing necessary in women diagnosed with non-mucinous high-grade epithelial ovarian cancer aged 80 years or older? |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913244/ https://www.ncbi.nlm.nih.gov/pubmed/36765687 http://dx.doi.org/10.3390/cancers15030730 |
work_keys_str_mv | AT morganrobertd isreflexgermlinebrca12testingnecessaryinwomendiagnosedwithnonmucinoushighgradeepithelialovariancanceraged80yearsorolder AT burghelgeorgej isreflexgermlinebrca12testingnecessaryinwomendiagnosedwithnonmucinoushighgradeepithelialovariancanceraged80yearsorolder AT flaumnicola isreflexgermlinebrca12testingnecessaryinwomendiagnosedwithnonmucinoushighgradeepithelialovariancanceraged80yearsorolder AT bulmanmichael isreflexgermlinebrca12testingnecessaryinwomendiagnosedwithnonmucinoushighgradeepithelialovariancanceraged80yearsorolder AT smithphilip isreflexgermlinebrca12testingnecessaryinwomendiagnosedwithnonmucinoushighgradeepithelialovariancanceraged80yearsorolder AT clampandrewr isreflexgermlinebrca12testingnecessaryinwomendiagnosedwithnonmucinoushighgradeepithelialovariancanceraged80yearsorolder AT hasanjurjees isreflexgermlinebrca12testingnecessaryinwomendiagnosedwithnonmucinoushighgradeepithelialovariancanceraged80yearsorolder AT mitchellclairel isreflexgermlinebrca12testingnecessaryinwomendiagnosedwithnonmucinoushighgradeepithelialovariancanceraged80yearsorolder AT salihzena isreflexgermlinebrca12testingnecessaryinwomendiagnosedwithnonmucinoushighgradeepithelialovariancanceraged80yearsorolder AT woodwardemmar isreflexgermlinebrca12testingnecessaryinwomendiagnosedwithnonmucinoushighgradeepithelialovariancanceraged80yearsorolder AT lalloofiona isreflexgermlinebrca12testingnecessaryinwomendiagnosedwithnonmucinoushighgradeepithelialovariancanceraged80yearsorolder AT crosbieemmaj isreflexgermlinebrca12testingnecessaryinwomendiagnosedwithnonmucinoushighgradeepithelialovariancanceraged80yearsorolder AT edmondsonrichardj isreflexgermlinebrca12testingnecessaryinwomendiagnosedwithnonmucinoushighgradeepithelialovariancanceraged80yearsorolder AT schlechthelene isreflexgermlinebrca12testingnecessaryinwomendiagnosedwithnonmucinoushighgradeepithelialovariancanceraged80yearsorolder AT jaysongordonc isreflexgermlinebrca12testingnecessaryinwomendiagnosedwithnonmucinoushighgradeepithelialovariancanceraged80yearsorolder AT evansdgarethr isreflexgermlinebrca12testingnecessaryinwomendiagnosedwithnonmucinoushighgradeepithelialovariancanceraged80yearsorolder |