IntroductionBackground

BRCA1 and BRCA2 are tumour suppressor genes that play an important role in the repair of DNA damage. Women who inherit a pathogenic mutation in the BRCA1 or BRCA2 genes are at substantially higher risk of developing breast and ovarian cancer over their lifetime than the average woman. Estimates for lifetime breast cancer risk vary between studies and differ according to mutation location and family history but have been reported to be in the region of 45%–85% for female BRCA1 mutation carriers and 27%–84% for female BRCA2 carriers to age 70 overall.1–13 Furthermore, some studies have reported that BRCA mutation carriers born in recent decades, have a substantially higher risk of developing breast cancer than those in earlier birth cohorts.7 14–16

Cumulative ovarian cancer risk to age 80 was estimated to be 44% for BRCA1 mutation carriers and 17% for BRCA2 mutations carriers in a study using data from a prospective cohort.1 This represents a significant risk compared with a population average of≤2%.17

Following a positive genetic test, women diagnosed as BRCA gene mutation carriers may be followed up in high-risk programmes for monitoring and management. Management strategies in this setting are aimed at early detection and/or prevention of the disease. Early detection strategies aim to diagnose breast cancer at an early stage to improve clinical outcomes; these include radiologic surveillance at regular intervals by mammography and MRI. Radiological screening techniques have not been proven to be effective in detecting ovarian cancer at an early stage. Prevention strategies aim to reduce a woman’s risk of developing breast or ovarian cancer by means of prophylactic surgery (including risk-reducing bilateral mastectomy and/or bilateral salpingo-oophorectomy (BSO)) or risk-reducing medication (chemoprevention) with drugs such as tamoxifen, anastrozole or raloxifene to reduce breast cancer risk.18

For BRCA mutation carriers, decisions about which risk management strategies to choose are complex, personal and multifactorial. Each option has associated risks and anticipated outcomes, which women need to understand to make an informed decision regarding which interventions to choose. Decision aids (DAs) in various formats, have been developed internationally to support decision-making for BRCA mutation carriers. Such tools require sophisticated design to effectively support decision-making, communicate risk, and clarify patients’ values and preferences.19 DAs for BRCA mutation carriers have not yet been widely incorporated into routine clinical practice.

Rationale

In order to better understand the features of existing DAs for this population and to reveal which of these DAs may be appropriate for various populations of BRCA mutation carriers a scoping review of existing DAs designed to support decision-making around risk management for female BRCA mutation carriers was conducted.

The overarching goal of this scoping review was to explore the breadth of the literature in this field and to map evidence relevant to cancer risk-management DAs for female BRCA mutation carriers without a personal history of cancer. This information may be beneficial for designing new DAs or adapting existing DAs to support decision-making in terms of cancer risk management for female BRCA mutation carriers.

A scoping review can be used to identify, map and discuss certain characteristics in papers or studies.20 The aim of this review is to summarise the key characteristics (content, features and efficacy) of patient DAs for female BRCA mutation carriers who are as yet cancer unaffected. A scoping review approach can provide a broad overview of the landscape of the literature and is, therefore the most appropriate design for this evidence synthesis.21

Review question

The question that this scoping review aimed to answer is:

What are the characteristics of patient DAs that have been developed to support risk-management decision-making in cancer unaffected female BRCA mutation carriers?

Objectives

The objectives of this scoping review were:

To identify and summarise the key features of patient DAs that have been developed for or are applicable to cancer unaffected female BRCA mutation carriers to support decision-making in terms of choosing which cancer risk management options to opt for.

To map the evidence related to testing of these DAs.

Methods

This scoping review was conducted according to the Joanna Briggs Institute’s (JBI’s) scoping review methodological framework.20 In addition, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist was used for guidance.22 The published protocol for this scoping review is available here.23

Inclusion criteriaTypes of participants

This review considered studies on DAs for cancer risk management designed for or applicable to women with a pathogenic BRCA1 or BRCA2 mutation who are unaffected by breast or ovarian cancer.

Concept

The concept of interest in this scoping review is patient DAs for female BRCA mutation carriers to support decision-making around cancer risk-management options.

In the absence of a universally accepted definition for ‘decision aid’ we included DAs that were (1) described as such by their developers and/or (2) included in the Ottawa Hospital Research Institute’s patient DAs inventory24 and/or that in the author’s judgement could be considered a DA based on the DA definition provided by the International Patient Decision Aids Standards (IPDAS) Collaboration.25

Context

The context of this review is decision-making supports for female BRCA mutation carriers without a personal history of breast or ovarian cancer. Sources of evidence on cancer risk management patient DAs for BRCA mutation carriers pertaining to any contextual setting were eligible for inclusion.

Types of evidence sourcesIncluded

(1) Studies that describe the development and/or testing of a patient DA suitable for cancer unaffected female BRCA mutation carriers to support decision-making in terms of choosing which cancer risk management options to opt for; (2) standalone DAs applicable to this population (ie, those that are available publicly but whose development has not necessarily been reported in a journal article); and (3) systematic reviews of the above-mentioned evidence sources.

Excluded

This review did not include case reports, non-systematic reviews, protocols, letters, posters or conference abstracts. Studies that described patient DAs aimed solely at BRCA mutation carriers with a personal history of breast or ovarian cancer were excluded. Patient DAs that focused on interventions that do not manage or reduce cancer risk (such as genetic testing, breast reconstruction or hormone replacement therapy) were also excluded.

Search strategy

A three-step search strategy was used. First, an initial limited search of the databases MEDLINE (Ovid) and EMBASE was conducted. This initial search was followed by an analysis of the text words contained in the title and abstract of retrieved papers, and of the index terms used to describe the articles. A second search using identified keywords and index terms was then be undertaken across all included databases (MEDLINE, EMBASE, CINAHL, Web of Science) (online supplemental appendix 1). Databases were searched from inception to 6 October 2020. No restrictions were applied for language or publication date. The reference lists of reports and articles selected for inclusion in the review were also searched for additional sources. Finally, a manual search of the internet using Google Scholar and The Ottawa Hospital Research Institute Decision Aid Library Inventory (decisionaid.ohri.ca) was conducted on 9 March 2022.

Evidence source selection

Search results were uploaded to EndNote X8 (Clarivate Analytics, PA, USA) and duplicate records were removed. Retrieved studies were initially screened for inclusion by title and abstract by two review authors independently using the web-based Covidence screening tool (Veritas Health Innovation, Melbourne, Australia). Disagreements were resolved by discussion. Full-text papers and reports were retrieved for potentially relevant studies. For these studies, Covidence software was again used to assess and document studies for inclusion and exclusion according to the inclusion criteria. Studies for inclusion were selected independently by two review authors. Disagreements were resolved by discussion. In cases of no consensus, final resolution was achieved by involving a third review author as arbiter.

Data extraction

Data were extracted from included articles and other evidence sources using a data extraction form developed by the reviewers, pilot tested and modified in an iterative process to produce the final version (online supplemental appendix 2). The design of this instrument is based on the JBI instrument for extracting details of the studies characteristics and results. Data extraction was performed independently by two reviewers. Disagreements between the reviewers were resolved through discussion. Extracted data were tabulated.

Patient and public involvement

Patients and public were not formally involved in the development of this scoping review protocol; however, the research questions were informed by the author team’s extensive clinical experience working with BRCA mutation carriers.

Deviations from the protocol

The data extraction template was amended from that published with the protocol to include additional fields to capture pertinent data identified during pilot testing (online supplemental appendix 2).

Discussion

This scoping review has mapped evidence relevant to cancer risk-management DAs that are applicable to female BRCA mutation carriers without a personal history of cancer. Specifically, we have identified and described the features of cancer risk-management DAs for this population and reported on the efficacy testing of these DAs where this has been conducted.

Two other systematic reviews on this topic have been published by Krassuski et al43 58 as well as a further study that incorporated a survey of existing DAs.40

Krassuski et al conducted a structural analysis and quality assessment of DAs for BRCA mutation carriers (with or without breast/ovarian cancer) and examined their applicability to the German context.58 In this study they identified 20 patient DAs of which nine met fundamental IPDAS quality criteria. The authors reported that some DAs differed markedly in content from the recommendations of German guidelines.

Krassuski et al conducted a systematic review of effectiveness of DAs for BRCA mutation carriers (with or without breast/ovarian cancer) that have been tested in randomised control trials or pretest and post-test studies. This study reported that DAs significantly improved decision related outcomes in female BRCA mutation carriers, though the authors noted bias concerns regarding most of the included studies.43

Kautz-Freimuth et al incorporated a review of existing DAs for BRCA mutation carriers as part of their development process for new DAs targeted towards German BRCA mutation carriers. Seven DAs were included in this review and an overview of the structural elements and basic medical contents of these DAs was provided. The authors concluded that due to various limitations related to content of the DAs; none were transferable to the German setting.40

Our scoping review differs from these articles in a number of ways. The population of interest for our study was BRCA mutation carriers without a personal history of breast or ovarian cancer often termed ‘previvors’. As such, DAs developed solely for cancer affected women were excluded from this review. In addition, as a scoping review we took a broader approach in terms of included evidence sources by combining a synthesis of features of existing DAs that can be used by cancer unaffected BRCA mutation carriers, the efficacy testing of these DAs and systematic reviews of same. As such, we believe that this work is a useful resource for clinicians and researchers which maps current evidence relating to features and efficacy of existing DAs for cancer unaffected BRCA mutation carriers in a single paper.

The findings described here therefore build on, complement and include those reported by Krassuski and colleagues.40 43 58

Our findings demonstrate that only four DAs have been developed exclusively for known BRCA mutation carriers without a personal history of cancer ‘previvors’.28 40 53 54 Considering the unique issues that these women face in relation to their high cancer risk and decision-making about their risk management, DAs designed exclusively for this group may be more appropriate.

Furthermore, of the DAs designed exclusively for cancer unaffected BRCA mutation carriers, only two included the full range of guideline18 recommended breast and ovarian cancer risk management strategies53 54 and only one of these is readily available publicly in its full version.53

The included DAs span a period of >20 years in terms of their date of development or last update. It is likely that time since development/update may have impacted content and features of DAs. For example, DAs developed recently were more likely to be web-based with four of the six DAs developed in the last 5 years having a web-based format. Furthermore, the evidence base in the BRCA field is continuously evolving. It is noteworthy that content included in some DAs is not in line with current evidence. For example, current evidence does not support screening for ovarian cancer as a valid risk management option for BRCA mutation carriers, therefore, DAs that include this as a risk management option53 55–57 may no longer be appropriate for use in their current version.

In addition, breast cancer risk reduction was listed as a benefit of BSO in eight DAs.29 33–36 39 53 54 Due to the conflicting evidence in relation to this60–62 it may be inappropriate to include breast cancer risk reduction as a benefit of BSO for BRCA1 mutation carriers in DAs presently.

Thus, currently there is no DA publicly available that has been designed exclusively for cancer unaffected BRCA mutation carriers, that includes all breast and ovarian risk management strategies recommended for this population together with a values clarification activity and that aligns with current best evidence in the field.

In terms of effectiveness of the existing DAs for BRCA mutation carriers; the included studies all reported a positive effect of the DA in question on at least one decision related or information related outcome. However, only six DAs were tested in an RCT, and bias concerns have been raised in relation to most of these RCTs.43 In addition, various instruments were used to assess outcomes in the DA effectiveness studies, some of which were validated and others not. Furthermore, it is possible that publication bias may have contributed to an over-representation of positive findings on DA effectiveness in the literature. Publication bias was not formally evaluated in this scoping review. Thus, while the reported effectiveness of these DAs in improving various decision and information related outcomes is promising; further high-quality studies using validated instruments are required to clarify the influence of DAs on these outcomes.

Limitations of this review

This scoping review has several limitations. As the intention of this study was to map the landscape of the evidence on development and testing of DAs applicable to cancer unaffected BRCA mutation carriers we took an inclusive approach to eligibility of evidence sources for inclusion. In the absence of a universally accepted definition for ‘decision aid’ we included DAs that were described as such by their developers and/or included in the Ottawa Hospital Research Institute’s patient DAs inventory and/or that in the author’s judgement could be considered a DA based on the DA definition provided by the IPDAS Collaboration.59 In addition, DAs included in this review were identified by searching databases, reference lists and the internet. It is possible that other relevant DAs may exist elsewhere in the grey literature. Several of the included DAs were not readily accessible as full versions in the public domain; as such, details of their features and content were derived from the articles describing their development rather that the full DA version. This may have resulted in some DA features being omitted in this report. Finally, as a scoping review a formal quality appraisal of included evidence sources was not conducted thus the evidence on DA quality and the quality of studies testing DA effectiveness reported here was drawn from reports by other authors43 58 rather than an independent appraisal.

ConclusionsImplications for research or practice

The features of existing DAs and evidence relating to their efficacy testing reported here and by others will serve as a useful basis for identifying which DAs are suitable for various populations of BRCA mutation carriers and will assist in the development of new DAs for this population.