<p>A systematic review of international guidelines and recommendations for the genetic screening, diagnosis, genetic counseling, and treatment of <em>BRCA</em>-mutated breast cancer</p>

Abstract

PurposeTo conduct a systematic review of international guidelines on screening and management of patients with BRCA-mutated breast cancer (BC).MethodsMajor electronic databases (MEDLINE and Embase; N=8) and gray literature sources were searched (January 2007 to February 2018). Latest guideline recommendations on genetic screening, counseling, and BC treatment of BRCA mutation carriers were summarized. Guidelines specific to germline BRCA (gBRCA) mutation were captured where available.ResultsA total of 3,775 records were retrieved and 32 guidelines were included; Europe (n=16), USA (n=11), Canada (n=3), Australia (n=1), and Japan (n=1) were included. Across and within guidelines, genetic counseling was recommended at multiple points in the care pathway, though the format was not always clearly defined. US guidelines emphasized that BRCA mutation testing should occur after specialized genetic counseling; other European guidelines are less prescriptive. BRCA testing eligibility criteria differed, with some guidelines being less restrictive; US National Comprehensive Cancer Network (NCCN) BC guidelines specified that HER2-negative BC patients eligible for single-agent therapy are eligible for gBRCA testing. Fast-track BRCA testing is recommended in the Netherlands if treatment choice will affect survival, but in the UK only as part of clinical trials. More recent European (European School of Oncology–European Society for Medical Oncology 3rd International Consensus Guidelines for Breast Cancer in Young Women 2017, Arbeitsgemeinschaft Gynäkologische Onkologie 2017 in Germany) and US (NCCN) guidelines have updated recommendations regarding gBRCA-targeted poly(ADP-ribose) polymerase (PARP) inhibitor therapy in BC.ConclusionRegional and organizational guidelines differ for genetic screening, counseling, and treatment of patients with BRCA-mutated BC. Guideline harmonization would optimize identification and management of these patients.

Pathology of Hereditary Breast and Ovarian Cancer

“…Tumor and germline genetic testing is variably performed in patients affected by breast (92) and ovarian carcinomas (93). It has been shown that triaging women for genetic testing based on family history alone will miss up to 30% of affected individuals (94).…”

Identification of Women at Risk for Hereditary Breast and Ovarian Cancer in A Sample of 1000 Slovenian Women: A Comparison of Guidelines

“…It has recently been observed that the prevalence of BRCA pathogenic variant carriers is higher than previously estimated (38) and that current clinical guidelines fail to identify an important proportion of patients carrying the pathogenic variants (18,19,21,39). Consequently, recent updates of the referral guidelines recommend referral of women with less remarkable family history of cancer (8). Studies that examined older versions of NCCN guidelines for HBOC referral of women from the general population identi ed more women with each update (17,22,23).…”

“…However, it is less common to refer unaffected women to genetic counseling for gynecological cancers, even when they harbor a family history of cancer and genetic counseling and testing would provide important information for their cancer risk evaluation (7). Identi cation of a pathogenic variant in asymptomatic women presents an opportunity to tailor appropriate monitoring and surveillance for breast and other cancers, in addition to offering prophylactic, risk-reducing interventions (8). The process of genetic testing begins with a referral from a general practitioner or oncologist to a genetic counselor; therefore, patients strongly rely on physician identi cation and referral for genetic counseling.…”

Early Triple Negative Breast Cancer: Conventional Treatment and Emerging Therapeutic Landscapes

“…All international guidelines highlighted the importance to identify gBRCA1/2 mutations carriers by performing genetic counseling as early as possible during the course of disease in patients at risk of inherited disease, given the implication in decision-making process in terms of the type of surgery, radiotherapy, and systemic treatment either in neo-(adjuvant) and advanced settings [33].…”