308PGenetic screening, counselling, and treatment of BRCA mutation (BRCAm) carriers: A systematic review (SR) of international breast cancer (BC) guidelines

Carol A. Forbes, D Fayter, C Clar, K Reid, S de Kock, R Quek

ANNALS OF ONCOLOGY(2018)

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Abstract
Background: Considering the availability of BRCAm-targeted therapeutic drugs in BC and an evolving clinical guidelines landscape, an SR of international guidelines on screening and management of BRCAm BC patients was carried out. Methods: The current SR adhered to Cochrane’s guidance. Major electronic databases (eg, Medline & Embase; n = 7) and grey literature sources were searched (Jan 2007 to Dec 2017). Latest guideline reporting recommendations (and evidence grades) on genetic screening, counselling, and BC treatment of BRCAm carriers were summarised. Guidelines specific to germline (gBRCAm) (ie, hereditary) were captured where available. Results: 3775 records were retrieved and 33 guidelines from Europe (n = 17), USA (n = 11), Canada (n = 3), Australia (n = 1), and Japan (n = 1) were included. Genetic counselling was recommended at multiple points in the care pathway, though the format (eg, frequency, decision tools) was not always clearly defined. US guidelines emphasised BRCAm testing should occur after specialised genetic counselling; other European guidelines were less prescriptive. BRCA testing eligibility criteria differed with some guidelines being less restrictive; US NCCN BC guidelines specified that HER2- BC patients eligible for single-agent therapy should strongly consider gBRCAm testing, while also having separate more restrictive high-risk BRCA testing criteria. Similar restrictive criteria were observed in some European guidelines. Fast-track BRCAm testing was recommended in the Netherlands if treatment choice affects BC survival, but only as part of a clinical trial in the UK. Other guidelines suggest testing only if it affects therapy decisions. ESMO ABC3 guidelines recommended platinum therapy for advanced BRCAm BC; more recent ESO-ESMO BCY3 and US NCCN guidelines recommended newly approved gBRCAm-targeted PARP inhibitor therapy. Conclusions: Differences exist between regions and within organizations for guidelines regarding genetic screening, counselling, and treatment of BRCAm BC patients. Harmonisation of guidelines could optimise the identification and management of BRCAm BC patients. Editorial acknowledgement: Editorial and medical writing support funded by Pfizer Inc. were provided by Edwin Thrower, PhD, Mary Kacillas and Paula Stuckart of Ashfield Healthcare Communications, Middletown, Connecticut. Legal entity responsible for the study: Pfizer, Inc. Funding: Pfizer, Inc. Disclosure: C. Forbes, D. Fayter, S. de Kock: Employee: KSR Ltd. who were paid by Pfizer Inc. to carry out this work. C. Clar, K. Reid: Freelance reviewer working on behalf of KSR Ltd. who were paid by KSR Ltd to carry out this work. R. Quek: Employee: Pfizer Inc.
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Key words
brca mutation,international breast cancer,brcam,breast cancer,genetic screening
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