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bioRxiv · 10.1101/044024

Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients

Abstract

BackgroundAdvances in DNA sequencing have made gene testing fast and affordable, but adaptation of clinical services to capitalise on this for patient benefit has been slow. Ovarian cancer exemplifies limitations of current systems and potential benefits of increased gene testing. Approximately 15% of ovarian cancer patients have a germline mutation in BRCA1 or BRCA2 (collectively termed BRCA) and this has substantial implications for their personal management and that of their relatives. However, in most countries implementation of BRCA testing in ovarian cancer has been inconsistent and largely unsuccessful.\n\nMethodsWe developed a mainstream pathway in which BRCA testing was undertaken by cancer team members after 30 minutes online training. Patients with a mutation were sent a genetic appointment with their results. Cascade testing to relatives was performed via standard clinical genetic procedures.\n\nFindings207 women with ovarian cancer were offered gene testing through the mainstream pathway and all accepted. 33 (16%) had a BRCA mutation. The result informed management of 79% (121/154) women with active disease including 97% (32/33) women with a mutation. All mutation-positive women and ~3.5 relatives per family have been seen in genetics. Patient and clinician feedback was very positive. >95% found the pathway to be simple and effective. The pathway offers considerable reduction in time (~5-fold) and resource requirements (~13-fold) compared to the traditional genetic pathway. We estimate it would deliver {pound}2.6M NHS cost savings per year, and would allow implementation of national testing recommendations with existing infrastructure.\n\nInterpretationMainstream genetic testing is effective, efficient and patient-centred and offers a mechanism for large-scale implementation of BRCA gene testing in cancer patients. The principles could be applied in many other countries and to many other areas of genomic medicine.

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Angela George, Daniel Riddell, Sheila Seal, Sabrina Talukdar, Shazia Mahamdallie, Elise Ruark, Victoria Cloke, Ingrid Slade, Zoe Kemp, Martin Gore, Ann Strydom, Susana Banerjee, Helen Hanson, Nazneen Rahman, Mainstreaming Cancer Genetics (MCG) Programme. 2016-03-16. Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients. https://doi.org/10.1101/044024

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