Introduction/Background Pathology-based ‘reflex’ tumour testing for BRCA variants in tubo-ovarian carcinomas (OC) has been proposed as patient-friendly, efficient and cost-effective approach to pre-select women for germline testing and stratify for eligibility of PARP-inhibitor therapy. The aim of this study was to review our first two years‘ experience of a ‘tumour first’ approach BRCA screening in our region, using a previously validated BRCA tumour test.
Methodology BRCA reflex testing for OC has been introduced in September 2017. The tumour test consisted of targeted Next Generation Sequencing (NGS) for detection of BRCA and (since July 2018) 13 additional HR genes in combination with BRCA1-specific copy number variant Multiplex Ligation-dependent Probe Amplification (MLPA). All detected variants and patient characteristics were extracted from the pathology reports. Follow-up data for patients with a likely or known pathogenic variant were collected from the clinical genetics.
Results 99 reflex BRCA tumour tests were performed on 69 (69.7%) high grade serous carcinomas (HGSC), 12 (12.1%) low grade serous carcinomas, 8 (8%) mucinous carcinomas, 5 (5.1%) endometrioid carcinomas and 5 (5.1%) clear cell carcinomas. Tumour DNA was isolated from 68 (68.7%) resection specimens, 24 (24.2%) biopsies and seven (7.1%) ascites fluid. NGS and MLPA success rate was 100% and 94.6% respectively. 30 (30.3%) OC harboured a variant: 15 (15.2%) pathogenic variants, 6 (6.1%) likely pathogenic variants and 9 (9.1%) variants of uncertain significance. All cases with either a pathogenic or likely pathogenic variant were HGSC. Of the 19/21 (90.4%) patients for which genetic testing was advised, 13 (68.4%) underwent genetic testing and 6/13 cases (46.2%) harboured a germline variant.
Conclusion Reflex tumour testing confirmed its effectiveness and usefulness as a routine pre-screening tool for patients diagnosed with an EOC. Furthermore all pathogenic or likely pathogenic variants were found in HGSC, which would support a histotype-based tumour testing approach in the future.
Disclosure Nothing to disclose.
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