Validation of the pathology-adjusted Manchester scoring system in over 10 000 assessments of cases with breast and/or ovarian cancer

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Background Genetic testing for (likely) pathogenic variants (PVs) in BRCA1 / BRCA2 has been performed in Manchester since 1996, with molecular methods/techniques and eligibility criteria changing over time. In 2004, UK National Institute for Health and Care Excellence guidelines determined a 20% detection threshold, which reduced to 10% in 2013. The Manchester score (MS) was developed in 2004 to assess the likelihood of detecting PVs at the 10%/20% threshold and was updated to include pathology adjustment (2009/17). Current testing algorithms for NHS England are now closer to 5%, although an MS of 15 (=10%) and CanRisk of 10% are still backstop indications. We provide an update of MS on testing of nearly 10 000 breast and/or ovarian cancer (BC/OC) cases. Methods MS using pathology adjustment was applied to cases of non-Jewish BC/OC cases undergoing full screening of BRCA1/2 with testing for CNVs. Results Overall, 6744 BC and 3291 OC cases were tested. For BC, 453 (6.7%) PVs were detected in BRCA1 and 456 (6.8%) in BRCA2 (combined 13.5%). Combined detection with MS=13–14, 15–19 and 20–24 was 52/821 (6.3%), 168/1440 (11.7%) and 193/877 (22.0%), respectively. The MS 15–19 (10%) threshold held true for all age groups and BC pathology types, except grade 1 (very low detection). For OC, detection rates were 273 (8.3%) and 193 (5.9%) for BRCA1 and BRCA2 , respectively. Again, the 10%/20% threshold MS held true with MS=15–19=123/861 (14.3%) and 13–14=22/301 (7.3%). MS=11 gave a robust 5% threshold, although only 1/86 (1.2%) OC <30 years tested positive; this was 1/5 high-grade serous cancers. For sporadic OC >79 years, only 2/177 (1.1%) tested positive. Conclusions MS remains a robust algorithm for assessing likelihood of a BRCA1/BRCA2 PV for individuals with BC/OC.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.