{"id":1043,"date":"2025-11-19T17:00:15","date_gmt":"2025-11-19T17:00:15","guid":{"rendered":"http:\/\/sebigec.es\/blog\/?guid=03ff1e07f1df78e3652cd8fdd2e56f09"},"modified":"2026-01-20T14:16:17","modified_gmt":"2026-01-20T14:16:17","slug":"validation-of-the-pathology-adjusted-manchester-scoring-system-in-over-10-000-assessments-of-cases-with-breast-and-or-ovarian-cancer","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2025\/11\/19\/validation-of-the-pathology-adjusted-manchester-scoring-system-in-over-10-000-assessments-of-cases-with-breast-and-or-ovarian-cancer\/","title":{"rendered":"Validation of the pathology-adjusted Manchester scoring system in over 10 000 assessments of cases with breast and\/or ovarian cancer"},"content":{"rendered":"\n<sec><st>Background<\/st>\n<p>Genetic testing for (likely) pathogenic variants (PVs) in <I>BRCA1<\/I>\/<I>BRCA2<\/I> 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.<\/p>\n<\/sec>\n<sec><st>Methods<\/st>\n<p>MS using pathology adjustment was applied to cases of non-Jewish BC\/OC cases undergoing full screening of <I>BRCA1\/2<\/I> with testing for CNVs.<\/p>\n<\/sec>\n<sec><st>Results<\/st>\n<p>Overall, 6744 BC and 3291 OC cases were tested. For BC, 453 (6.7%) PVs were detected in <I>BRCA1<\/I> and 456 (6.8%) in <I>BRCA2<\/I> (combined 13.5%). Combined detection with MS=13&ndash;14, 15&ndash;19 and 20&ndash;24 was 52\/821 (6.3%), 168\/1440 (11.7%) and 193\/877 (22.0%), respectively. The MS 15&ndash;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 <I>BRCA1<\/I> and <I>BRCA2<\/I>, respectively. Again, the 10%\/20% threshold MS held true with MS=15&ndash;19=123\/861 (14.3%) and 13&ndash;14=22\/301 (7.3%). MS=11 gave a robust 5% threshold, although only 1\/86 (1.2%) OC &lt;30 years tested positive; this was 1\/5 high-grade serous cancers. For sporadic OC &gt;79 years, only 2\/177 (1.1%) tested positive.<\/p>\n<\/sec>\n<sec><st>Conclusions<\/st>\n<p>MS remains a robust algorithm for assessing likelihood of a <I>BRCA1\/BRCA2<\/I> PV for individuals with BC\/OC.<\/p>\n<\/sec>\n","protected":false},"excerpt":{"rendered":"<p>Background<br \/>\nGenetic 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 &#8230;<\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,14],"tags":[83],"class_list":["post-1043","post","type-post","status-publish","format-standard","hentry","category-articulos","category-jmg","tag-jmedgenet"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/1043","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=1043"}],"version-history":[{"count":2,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/1043\/revisions"}],"predecessor-version":[{"id":6817,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/1043\/revisions\/6817"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=1043"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=1043"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=1043"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}