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Is Reflex Germline BRCA1/2 Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older?

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.

SUBMITTER: Morgan RD

PROVIDER: S-EPMC9913244 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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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 RD Burghel George J GJ Flaum Nicola N Bulman Michael M Smith Philip P Clamp Andrew R AR Hasan Jurjees J Mitchell Claire L CL Salih Zena Z Woodward Emma R ER Lalloo Fiona F Crosbie Emma J EJ Edmondson Richard J RJ Schlecht Helene H Jayson Gordon C GC Evans D Gareth R DGR

Cancers 20230125 3

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 germl ...[more]

PMID: 36765687

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Project description:BackgroundBRCA1 expression can be lost by a variety of mechanisms including germline or somatic mutation and promotor hypermethylation. Given the potential importance of BRCA1 loss as a predictive and prognostic biomarker in high-grade serous ovarian cancer, we sought to evaluate the utility of BRCA1 immunohistochemistry (IHC) in screening for BRCA1 loss by germline, somatic, and epigenetic mechanisms.Patients and methodsPatients with advanced high-grade serous ovarian cancer who had previously undergone germline BRCA1 testing were identified. Samples from each tumor were stained for BRCA1 and reviewed independently by two pathologists blinded to BRCA status. Tumors with abnormal BRCA1 IHC and wild-type germline testing underwent further evaluation for somatic BRCA1 mutations and promoter hypermethylation. McNemar's test was used to determine the association of BRCA1 IHC with germline BRCA1 mutations and BRCA1 loss through any mechanism. Kaplan-Meier methods were used to estimate overall survival (OS), and the log-rank test was used to assess differences between groups.ResultsInter-rater reliability between the two pathologists on BRCA IHC interpretation was very good (kappa coefficient 0.865, P = 0.16; McNemar's test). BRCA1 IHC was abnormal in 36% (48/135) of cases. When compared with germline BRCA1 status, BRCA1 IHC had a high negative predictive value (95.4%) but a low positive predictive value (PPV, 52.1%). When accounting for promoter hypermethylation and somatic mutations as alternative methods of BRCA1 loss, the PPV rose to 87.5%. Five-year OS rate was 49.6% [95% confidence interval (CI) 26.3% to 69.3%] for patients with germline BRCA1 mutations, 50.4% (95% CI 27.5% to 69.5%) for germline wild-type BRCA1 and abnormal IHC, and 52.1% (95% CI 38.4% to 64.2%) for germline wild-type BRCA1 and normal IHC (P = 0.92).ConclusionsBRCA1 IHC interpretation was a highly reproducible and accurate modality for detecting germline, somatic, or epigenetic mechanisms of BRCA1 loss. These results support further development of BRCA1 IHC as a potential biomarker for BRCA1 loss in high-grade serous ovarian cancer.

Project description:ImportanceContemporary data on use of eye care by US adults are critical, as the prevalence of age-related eye disease and vision impairment are projected to increase in the coming decades.ObjectivesTo provide nationally representative estimates on self-reported use of eye care by adults aged 50 to 80 years, and to describe the reasons that adults do and do not seek eye care.Design, setting, and participantsThe National Poll on Healthy Aging, a cross-sectional, nationally representative online survey was conducted from March 9 to 24, 2018, among 2013 individuals aged 50 to 80 years.Main outcomes and measuresThe proportion of US adults who received an eye examination within the past 2 years as well as the sociodemographic and economic factors associated with receipt of eye care.ResultsAmong 2013 adults aged 50 to 80 years (survey-weighted proportion of women, 52.5%; white non-Hispanic, 71.1%; mean [SD] age, 62.1 [9.0] years), the proportion reporting that they underwent an eye examination in the past year was 58.5% (95% CI, 56.1%-60.8%) and in the past 2 years was 82.4% (95% CI, 80.4%-84.2%). Among those with diabetes, 72.2% (95% CI, 67.2%-76.8%) reported undergoing an eye examination in the past year and 91.3% (95% CI, 87.7%-93.9%) in the past 2 years. The odds of having undergone an eye examination within the past 2 years were higher among women (adjusted odds ratio [AOR], 2.00; 95% CI, 1.50-2.67), respondents with household incomes of $30 000 or more (AOR, 1.57; 95% CI, 1.08-2.29), and those with a diagnosed age-related eye disease (AOR, 3.67; 95% CI, 2.37-5.69) or diabetes (AOR, 2.30; 95% CI, 1.50-3.54). The odds were lower for respondents who were unmarried (AOR, 0.71; 95% CI, 0.53-0.96), from the Midwest (AOR, 0.55; 95% CI, 0.34-0.87) or West (AOR, 0.60; 95% CI, 0.38-0.94), or reported fair or poor vision (AOR, 0.43; 95% CI, 0.28-0.65). Reasons reported for not undergoing a recent eye examination included having no perceived problems with their eyes or vision (41.5%), cost (24.9%), or lack of insurance coverage (23.4%).Conclusions and relevanceIn this study, the rate of eye examinations was generally high among US adults aged 50 to 80 years, yet there were several significant demographic and socioeconomic differences in the use of eye care. These findings may be relevant to health policy efforts to address disparities in eye care and to promote care for those most at risk for vision problems.

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Is Reflex Germline BRCA1/2 Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older?

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Is Reflex Germline <i>BRCA1/2</i> Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older?

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Dataset Information

Is Reflex Germline BRCA1/2 Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older?

Publications

Is Reflex Germline &lt;i&gt;BRCA1/2&lt;/i&gt; Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older?

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OmicsDI is part of the ELIXIR infrastructure

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Is Reflex Germline <i>BRCA1/2</i> Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older?