European experts consensus: BRCA/homologous recombination deficiency testing in first-line ovarian cancer

Abstract

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Toward More Comprehensive Homologous Recombination Deficiency Assays in Ovarian Cancer, Part 1: Technical Considerations

“…BRCA1 mutation carriers exhibit OC at a younger age than BRCA2 mutation carriers. The high prevalence of BRCA1/2 mutations led to the formulation of international guidelines to integrate genetic testing, or at least genetic counseling, upon EOC diagnosis, particularly in the context of a familial history of OC [ 10 , 11 , 12 , 13 ]. Furthermore, prophylactic risk-reducing bilateral salpingo-oophorectomy has been shown to be an effective prevention strategy in germline BRCA1/2 carriers [ 14 ].…”

“…The rate of variants of unknown significance (VUS), which was originally 84% during initial BRCA testing development, has dropped to approximately 10% due to VUS reclassification and refinement, notably through the Consortium of Investigators of Modifiers of BRCA (CIMBA) [ 114 ]. However, non- BRCA HR-related genes, when used in some randomized controlled trials (RCTs) evaluating PARPis or Pt-S in HGSOC, have produced conflicting results and are currently under investigation [ 11 , 12 , 40 , 42 ].…”

“…As gBRCA* represents the vast majority of tBRCA* and has important implications for the hereditary risk of breast and ovarian cancers (HBOC) and screening of patient relatives, current guidelines systematically recommend referral to genetic counseling upon tBRCA* detection [ 11 , 12 , 115 , 116 ]. Evaluation of gBRCA needs to be performed both at the micro- and macro-lesion scales, as LR constitutes a non-negligible fraction of BRCA alterations.…”

Toward More Comprehensive Homologous Recombination Deficiency Assays in Ovarian Cancer Part 2: Medical Perspectives

“…Owing to their clinical impact, FF-CDx and MC-CDx (both FDA-approved assays) have been included as part of epithelial ovarian cancer management in the recommendations of the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) [ 40 , 45 ]. However, a recently published expert consensus identified the urgent need to develop new tools that can more accurately assess HRD status in HGSOC cases [ 46 ].…”

Noncoding RNAs in the Glycolysis of Ovarian Cancer

“…Ovarian cancer (OC) is currently the most deadly gynecologic malignancy with insidious and rapidly progressive onset. Most patients have advanced pelvic and abdominal metastases by the time of diagnosis, and the 5-years survival rate is only 20–30% worldwide ( Vafadar et al, 2020 ; DiSilvestro et al, 2021 ; Vergote et al, 2021 ). OC account for 5% of all cancer deaths in women ( Yang et al, 2021 ; Youssef et al, 2021 ) due to the low survival rates resulting from late diagnosis.…”