Key words
BRCA1
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BRCA2
- decision aid - familial breast cancer - familial ovarian cancer
Introduction
About one to three in a thousand women carry a pathogenic mutation in one of the two risk genes BRCA1 and BRCA2 (BReast CAncer genes 1 and 2)
[1], [2], [3], [4]. They have a markedly increased risk of developing breast (BC) and/or ovarian cancer (OC) in the course of their life. According to population-based studies, the cumulative risk of BRCA1 mutation carriers is 72% for BC and 44% for OC up to the age of 80 years [5]. Corresponding estimates for BRCA2 are 69% and 17% [5]. In addition, patients with unilateral BC have a markedly increased risk of developing contralateral BC also, compared with the general population [5]. Women can be tested genetically if there is justified suspicion of BRCA1/2 mutation [6], [7]. A positive gene result often confronts the women with difficult decisions. Mutation carriers without cancer must consider their personal values and life situation when deciding how to deal with the increased disease risk. Adequate understanding of risks is a fundamental precondition for decision-making. Women who already have unilateral BC must also consider various competing risks when deciding, such as the risk of ipsilateral recurrence or metastasis of the primary tumour. Current prevention and screening strategies that can be offered to mutation carriers include an intensified BC screening programme for women without BC (breast magnetic resonance imaging, breast ultrasound, mammography, medical breast palpation), an intensified BC screening and follow-up programme for women who already have BC and risk-reducing surgery of the breast and adnexa [7], [8], [9], [10] ([Table 1]).
Table 1 Prevention strategies for BRCA1/2 mutation carriers in Germany.
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BRCA1/2: BReast CAncer gene 1/2, MRI: magnetic resonance imaging, BC: breast cancer, OC: ovarian cancer, BMI: body mass index
1 [9]
2 [10]
3 AGO: to identify early stages of BC (Oxford evidence level 2b).
4 Or until good mammographic assessability is reached.
5 AGO: to identify early stages of BC (Oxford evidence level 2a), to reduce mortality (Oxford evidence level 3a).
6 [8]
7 [7]
8 AGO: reduces OC incidence, OC mortality and overall mortality (Oxford evidence level 2a). S3 OC guideline: reduces OC incidence and mortality (SIGN evidence level 2+). S3 BC guideline: reduces OC incidence and overall mortality (Oxford evidence level 2a).
9 After family is complete and taking into account the earliest age of disease in a family member.
10 AGO: reduces OC incidence and mortality and overall mortality (Oxford evidence level 2b). S3 BC guideline: reduces BC and overall mortality (Oxford evidence level 2a).
11 AGO: reduces BC incidence (Oxford evidence level 2a) and BC mortality in BRCA1-positive women (Oxford evidence level 2b). S3 BC guideline: reduces BC incidence, reduction in BC mortality “not conclusively confirmed” (Oxford evidence level 2a).
12 AGO: reduces contralateral BC incidence and mortality (Oxford evidence level 2b). S3 BC guideline: reduces contralateral BC incidence (Oxford evidence level 2a).
13 AGO: reduces the risk for invasive BC, ductal carcinoma in situ and lobular neoplasia (Oxford evidence level 1a).
14 AGO: reduces the risk for invasive BC (Oxford evidence level 1b).
15 AGO: Anastrozole reduces the risk for OC, endometrial, colorectal, skin, thyroid, urinary tract and haematological cancers (Oxford evidence level 1b).
16 S3 BC guideline: in oestrogen receptor-positive BC guided by pharmacological prevention recommendations for sporadic BC.
17 AGO: reduces the incidence of contralateral BC (Oxford evidence level 2b).
18 [11]
19 AGO: general recommendations on BC prevention for women (BRCA-positive and negative). S3 OC guideline: increased BMI increases the OC risk.
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Intensified breast screening programme1, 2
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Women without cancer3
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≥ 25 years
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Half-yearly
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≥ 25 to 70 years
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Half-yearly
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≥ 40 to 70 years
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Every one to two years
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≥ 25 to 70 years4
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Annually
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Women with unilateral BC5
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≥ 25 years
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Half-yearly
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≥ 25 to 70 years
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Half-yearly
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≥ 40 to 70 years
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Every one to two years
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≥ 25 to 70 years4
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Annually
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Risk-reducing bilateral salpingo-oophorectomy1, 6, 7
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Without cancer, BRCA1 8
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≥ 35 – 40 years9
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recommended
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Without cancer, BRCA2 8
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≥ 40 – 45 years9
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recommended
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Women with unilateral BC10
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Risk-reducing bilateral or contralateral mastectomy1, 7
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Women without cancer11
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Individual decision after detailed, non-directive counselling.
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Women with unilateral BC12
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Pharmacological prevention1, 7
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Currently no general recommendations for pharmacological prevention by the German Breast and Ovarian Cancer Consortium.
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Women without cancer
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Pharmacological preventive measures should be considered only after detailed counselling and taking the individual risk profile and age into account.1
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> 35 years
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postmenopausal
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postmenopausal
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Women with unilateral BC16
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Life style1, 18, 19
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BMI 18,5 – 25 kg/m2, prevention/good control of diabetes mellitus, reduction of alcohol consumption, no smoking, healthy diet (e.g., Mediterranean diet), physical activity
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Without comprehensive counselling and an adequate understanding of risk, decision conflicts may arise in BRCA1/2 mutation carriers. Decision conflicts can lead to regretting important decisions or making recriminations [12], [13], [14], [15]. Brehaut et al. showed the former in cohorts of women (hormone replacement therapy, adjuvant BC therapy) and men (prostate cancer therapy) [13], and the latter was found by Gattellari and Ward in a cohort of men (prostate specific antigen test) [14]. The right to be advised and informed was strengthened by the Patient Rights Act [16] and the importance of evidence-based patient information for decision-making was emphasised in the National Cancer Plan [17]. In Germany the
information medium offered to patients to date has mainly been leaflets, which do not go beyond informing about the different treatment options. Decision aids (DAs) that in addition give the user the possibility of clarifying their own values and preferences as well as weighing treatment options are becoming increasingly important nationally and internationally. The International Patient Decision Aid Standards (IPDAS) Collaboration defines DAs as “tools designed to help people participate in decision making about health care options. They provide information on the options and help patients clarify and communicate the personal value they associate with different features of the options” [18]. DAs are used alone or in combination with other decision-making support tools, such as decision coaching, a non-directive discussion between a person seeking advice and trained health personnel [19].
DAs assist in weighing the benefits and risks of different treatment options and in clarifying oneʼs own values and preferences [18], [20]. They are helpful especially for complex decision when
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There is more than one appropriate option,
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No option has a clear advantage as regards the health outcome,
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The options are preference-sensitive, that is, they are associated with advantages, disadvantages and uncertainties that can be assessed differently by the user,
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The evidence is limited [18], [20].
The quality of a decision can be increased by DAs [20], [21]. A decision is high-quality or, as OʼConnor terms it, “effective” when it is informed and in agreement with oneʼs own values and is acted on accordingly [22].
In recent years, several DAs have been developed internationally for BRCA1/2 mutation carriers. These have not yet been collated systematically or classified with regard to their content or quality. In Germany to date, no DAs for BRCA1/2 mutation carriers are provided routinely in clinical practice. Two German DAs were developed in conjunction with the present study and are currently undergoing clinical investigation [23], [24]. The aim of this study is
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To provide a completely up-to-date systematic overview of available DAs for BRCA1/2 mutation carriers,
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To record the formal criteria of the DAs,
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To analyse the medical content of the DAs and
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To assess their quality.
Material and Methods
Search strategy
A systematic literature search was performed in MEDLINE, Embase, PsycINFO, ERIC and the Cochrane Database of Systematic Reviews. The search strategy was adapted individually to each database and comprised two categories of terms: decision-making/decision aid and BRCA1/2 (Appendix 1). The search followed the PRISMA guidelines [25]. The bias potential of the studies was not investigated as this was already done in a previous article [21] and the focus of this article was not on the screened studies but on the DAs described therein. In addition, a manual search was performed using Google and on the websites of various institutions (e.g., Ottawa Hospital Research Institute). The IPDAS Collaboration definition of DA was used in the search [18].
Inclusion criteria
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Documents that are designated by the authors as DA, without limitation of the format, including
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DAs that are described in primary studies, without limitation of the study design plus
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DAs that can be accessed on the internet.
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Target group of the DA: women aged 18 to 75 years with positive BRCA1/2 genetic test result.
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Content of the DA: preventive treatment alternatives for confirmed pathogenic BRCA1/2 mutation.
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Languages of the DA: German, English, French, Spanish, Italian, Dutch.
Exclusion criteria
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DAs on the question of whether genetic testing for a BRCA1/2 mutation should be performed,
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DAs on communicating a positive BRCA1/2 genetic test result to relatives,
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DAs on questions about family planning if there is a positive BRCA1/2 genetic test result,
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Other forms of decision support, e.g., decision coaching.
Screening
Screening of titles, abstracts and full texts was performed by two reviewers independently. A third reviewer was added in the event of disagreements in the screening process. The DAs described in the primary studies were requested or, if available, accessed online.
Analysis of formal criteria
The included DAs were analysed according to formal criteria: target group addressed, publication year or last update, site of production, language and format.
Analysis of content criteria
The content was analysed as to whether the offered treatment alternatives refer to the prevention of BC, OC or both diseases, which options are named specifically, which tools are offered to support decision making, what information is present and whether it is possible to individualise information.
Analysis of qualitative criteria
The quality of the DA was examined with the aid of the International Patient Decision Aid Standards tool (IPDASi v4.0). This comprises 44 criteria in ten dimensions (information, probabilities, values, support of decision-making, decision-making, development process, evidence, disclosure, readability, evaluation, diagnostic test). The IPDASi dimension “Diagnostic test” was not included as it does not apply for the present study aim and as a DA. The IPDASi criteria are divided into three groups: qualification criteria, certification criteria and quality criteria ([Table 6]). The qualification criteria were given a binary assessment (yes/no) and define a DA as such. The certification criteria, which are assessed on a scale of 1 to 4, are intended to avoid decision bias. If a DA is to be certified as such, each certification criterion must reach a score of at least 3. The quality criteria are desirable as they increase the quality of the DA
but are not essential (assessment scale from 1 to 4). The quality of the DA was assessed independently by two reviewers. A third reviewer was included if the assessments differed.
Results
Search results
Twenty DAs in total were included ([Fig. 1]). Ten DAs are described in primary studies and were found in the database search [27], [28], [29], [30], [31], [32], [33], [34], [35], [36]. Six of these were available as full version [28], [29], [32], [33], [34], [35]. Four DAs were not available as full version as two authors could no longer access the DA [27], [31], the
format of the DA was no longer in use [36] or our enquiry was not answered [30]. Ten other DAs were identified by manual search and were available for further analysis [37], [38], [39], [40], [41], [42], [43], [44], [45], [46].
Fig. 1 Flowchart of the search results based on the PRISMA guidelines [25]. Search results of the systematic literature search in MEDLINE, Embase, PsycINFO, ERIC and the Cochrane Database of Systematic Reviews; the search strategy included the two categories decision-making/decision aid and BRCA1/2. A manual search was performed in addition. DA: decision aid(s). Date of the last database search: 29.10.2019. Date of the last manual search: 31.12.2019.
Formal criteria
All 20 included DAs could be used for formal assessment. They were published between 2003 and 2019 ([Table 2]). Nine DAs were produced explicitly for BRCA1/2 mutation carriers [27], [28], [29], [30], [31], [33], [34], [35], [36], and eleven were additionally addressed to women who have an increased OC and/or BC risk for other reasons [32], [37] – [46]. These include increased familial incidence of OC and/or BC [32], [37] – [44], Lynch syndrome [38], [40], [41], [43], [44], TP53, STK11, PTEN or E-cadherin mutation [45], [46] and radiotherapy of the thorax [42]. Of the nine DAs produced explicitly for BRCA1/2 mutation carriers, one is addressed exclusively to women with a history of BC [27] and four are addressed exclusively to women who so far have neither BC nor OC [28], [29], [30], [33]. Nine DAs were developed in the USA [27], [29], [31], [33], [36], [37], [40], [42], [43], four in Australia [32], [38], [39], [44], three in the United Kingdom [41], [45], [46], two in Canada [28], [30] and two in the Netherlands [34], [35]. All except the last two are written in English. Thirteen DAs are web-based or accessible online [27], [29], [32], [33], [37], [39], [40], [41], [42], [43], [44], [45], [46] and seven were produced in paper, video or CD-ROM format [28], [30], [31], [34], [35], [36], [38]. Information about how the women could access the DAs could not be analysed as there was no clear information in this regard in several DAs or in the corresponding studies.
Table 2 Basic decision aid data.
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Title
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Developer
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Publication year or last update
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Origin
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Format
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Target group
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Treatment alternatives offered
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BRCA1/2: BReast CAncer gene 1/2, BC: breast cancer, DA: decision aid(s), OC: ovarian cancer, BC-S: breast cancer screening, OC-S: ovarian cancer screening, RR-M: risk-reducing mastectomy, RR-BM: risk-reducing bilateral mastectomy, RR-O: risk-reducing oophorectomy, RR-BO: risk-reducing bilateral oophorectomy, RR-S: risk-reducing salpingectomy, RR-SO: risk-reducing salpingo-oophorectomy, RR-BSO: risk-reducing, bilateral salpingo-oophorectomy, HRT: hormone replacement therapy
1 Focus on BC prevention based on title of the DA or authorsʼ information on the DA. Options for OC prevention are sometimes mentioned also.
2 Focus on OC prevention based on title of the DA or authorsʼ information on the DA. Options for BC prevention are sometimes mentioned also.
3 Currently not accessible online.
4 Information on target group from corresponding study.
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DA with preventive measures regarding BC and OC
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Keuzen bij een erfelijk verhoogd risico op borst- en/of eierstokkanker
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van Roosmalen
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2004
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Netherlands
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Brochure, video
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BRCA1/2 mutation carriers, with or without BC/OC (no RR-BM + RR-BO, no distant metastases)4
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BC-S (self-examination, medical examination, mammography, MRI), RR-M, OC-S, RR-O, pharmacological prevention (tamoxifen), use of oral contraceptives
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Individualized Survival Curves Improve Satisfaction With Cancer Risk Management Decisions in Women With BRCA1/2 Mutations
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Armstrong
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2005
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USA
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Brochure
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BRCA1/2 mutation carriers, with or without BC (no RR-BM + RR-BO, no BC with metastases, no OC)4
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BC-S, RR-M, RR-O, pharmacological prevention (tamoxifen, raloxifene), HRT
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Development an Evaluation of a Decision Aid for BRCA Carriers with Breast Cancer
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Culver
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2011
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USA
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Web-based
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BRCA1/2 mutation carriers aged > 21 years, with BC4
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BC-S (mammography, MRI), RR-M, RR-O, EK-F, pharmacological prevention (tamoxifen)
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Decision Tool for Women with BRCA Mutations
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Kurian
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2011
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USA
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Web-based
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BRCA1/2 mutation carriers aged 25 – 69 years, without cancer (no BC-S such as MRI or mammography, no RR-M, no RR-O, no RR-S, no preventive medication)
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BC-S (mammography, mammography + MRI), RR-M, RR-O
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BRCA decision aid (for unaffected BRCA+ women)
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Jabaley
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2019
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USA
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Web-based
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Healthy BRCA1/2 mutation carriers
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Intensified surveillance (BC-S including self-examination, medical examination, mammography, MRI; RR-SO; OC-S including CA-125 testing and vaginal ultrasonography), RR-M, RR-BSO, pharmacological prevention (tamoxifen or raloxifene), use of oral contraceptives
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DA with preventive measures regarding BC1
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Personal Aid to Health: Making Decisions that Work
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Kaufman
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2003
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USA
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CD-ROM
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BRCA1/2 mutation carriers aged 25 – 75 years, with or without BC/OC (no RR-BM, no metastases)4
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BC-S (self-examination, medical examination, mammography), RR-M, OC-S, RR-O, pharmacological prevention (tamoxifen, raloxifene), use of oral contraceptives
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What are my Options for Breast Cancer Prevention? Facts and Decision Aid for Women with a BRCA1 or BRCA2 Mutation
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Metcalfe
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2007
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Canada
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Brochure
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BRCA1/2 mutation carriers without BC/OC who are undecided with regard to a preventive measure4
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BC-S (self-examination, medical examination, mammography, MRI), RR-M, RR-SO, pharmacological prevention (tamoxifen)
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Information for women considering preventive mastectomy
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Centre for Genetics Education, NSW Health
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2012
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Australia
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Web-based, brochure
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Women with increased BC risk (BRCA1/2 mutation carriers, increased familial incidence of BC)
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BC-S (examinations, mammography, MRI), RR-M, pharmacological prevention (anastrozole), lifestyle (avoidance of hormones, fat-reduced diet, reduce alcohol consumption)
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Taking tamoxifen to reduce the chance of developing breast cancer. Decision aid for premenopausal women at high risk
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NICE
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2017
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United Kingdom
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Web-based, PDF
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Premenopausal women with increased BC risk (mutations in BRCA1/2, TP53, STK11, PTEN, E-cadherin), without BC
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No medication, tamoxifen daily for a period of 5 years
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Taking a medicine to reduce the chance of developing breast cancer. Decision aid for postmenopausal women at high risk
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NICE
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2017
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United Kingdom
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Web-based, PDF
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Postmenopausal women with increased BC risk (mutations in BRCA1/2, TP53, STK11, PTEN, E-cadherin), without BC
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No medication, tamoxifen daily for a period of 5 years, anastrozole daily for a period of 5 years, raloxifene daily for a period of 5 years
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iPrevent®
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Collins
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2017
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Australia
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Web-based
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Women including women with increased BC risk (age 18 – 70 years, no BC, no RR-BM, no radiotherapy of the breast, no mutations in cancer genes apart from BRCA1/2 in themselves or blood relatives, no half sibling with OC/BC/prostate cancer/pancreatic cancer)
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Personalised options for BC risk reduction
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Effect of decision aid for breast cancer prevention on decisional conflict in women with a BRCA1 or BRCA2 mutation: a multisite, randomized, controlled trial
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Metcalfe
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2017
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Canada
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Brochure
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BRCA1/2 mutation carriers aged 25 – 60 years, without BC/OC (no RR-M, no RR-O, no tamoxifen)4
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RR-M, RR-BSO, pharmacological prevention (tamoxifen)
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Breast Cancer: What Should I Do if Iʼm at High Risk?
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Healthwise
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2019
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USA
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Web-based
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Women with increased BC risk (BRCA1/2 mutation carriers, increased familial incidence of BC)
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BC-S (medical examinations, Mammography, MRT), RR-M, RR-O, pharmacological prevention (tamoxifen, raloxifene, aromatase inhibitors like anastrozole)
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Preventive (prophylactic) mastectomy: Surgery to reduce breast cancer risk
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Mayo Clinic
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2019
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USA
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Web-based
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Women with increased BC risk (BRCA1/2 mutation carriers, increased familial incidence of BC, radiotherapy of the thorax)
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BC-S (self-examination, medical examination, mammography, MRI), RR-M, P-O, pharmacological prevention (tamoxifen, raloxifene, exemestane, anastrozole), lifestyle (weight normalisation, physical activity, reduction of alcohol consumption, no HRT during menopause, Mediterranean diet)
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DA with preventive measures regarding OC2
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Risk Management options for women at increased risk of developing ovarian cancer. Information Booklet and Decision Aid
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Tiller
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2008
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Australia
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Brochure
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Women with increased OC risk aged ≥ 30 years, with or without BC (without OC; without RR-BO; no women in whom a risk mutation for OC was excluded)4
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Watchful waiting, OC-S, RR-SO, tubal ligation, hysterectomy, use of oral contraceptives, HRT
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OvDex. Oophorectomy Decision Explorer3
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Cardiff University
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2014
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United Kingdom
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Web-based, PDF
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Women with increased OC risk (BRCA1/2 mutation carriers, increased familial incidence of OC and/or BC, Lynch syndrome)
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RR-SO, lifestyle (healthy diet, healthy weight, physical activity), HRT
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Surgery to Reduce the Risk of Ovarian Cancer. Information for Women at Increased Risk
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Centre for Genetics Education, NSW Health
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2017
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Australia
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Web-based, brochure
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Women with increased OC risk (BRCA1/2 mutation carriers, increased familial incidence of OC, Lynch syndrome)
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RR-BSO (laparoscopy or laparotomy), hysterectomy, tubal ligation, use of oral contraceptives, HRT
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A patient decision aid for risk-reducing surgery in premenopausal BRCA1/2 mutation carriers: Development process and pilot testing
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Harmsen
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2018
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Netherlands
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Brochure
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Premenopausal BRCA1/2 mutation carriers4
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No operation, RR-SO, RR-S with delayed RR-O, HRT, no HRT
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Ovarian Cancer: Should I Have My Ovaries Removed to Prevent Ovarian Cancer?
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Healthwise
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2019
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USA
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Web-based
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Women with increased OC risk (BRCA1/2 mutation carriers, increased familial incidence of OC, Lynch syndrome)
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OC-S (CA-125 testing, vaginal ultrasonography), RR-O, use of oral contraceptives
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Prophylactic oophorectomy: Preventing cancer by surgically removing your ovaries
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Mayo Clinic
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2019
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USA
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Web-based
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Women with increased BC/OC risk (BRCA1/2 mutation carriers, increased familial incidence of OC and/or BC, Lynch syndrome)
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P-O, OC-S (CA-125 testing, vaginal ultrasonography), P-BM, HET, use of oral contraceptives
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Content
Based on their content, the DAs were divided into three groups: 5 of the 20 DAs (25%) describe preventive measures for both BC and OC [27], [29], [31], [33], [35], 9 (45%) focus on BC preventive measures [32], [37], [39], [42], [45], [46] and 6 (30%) on OC preventive measures [34], [38], [40], [41], [43], [44]. Further analysis of the contents of the DAs was possible only for the 16 DAs that were present in full version. The results are
presented in [Tables 3] to [5] and compared to the German guidelines. None of the existing DAs corresponds completely in content to the German recommendations.
Table 3 Content of the decision aids: treatment alternatives for breast cancer prevention.
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Recommendations in Germany3
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S3 BC guideline, women without BC
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S3 BC guideline, women with BC
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AGO Guidelines Breast, women without BC
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AGO Guidelines Breast, women with BC
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S3 OC guideline
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Decision aids
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With preventive measures regarding BC and OC
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With preventive measures regarding BC19
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With preventive measures regarding OC24
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Developer
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van Roosmalen
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Armstrong
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Culver
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Kurian
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Jabaley
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Kaufman
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Metcalfe
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Centre for Genetics Education, NSW Health
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NICE (premenopausal)
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NICE (postmenopausal)
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Metcalfe
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Collins
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Healthwise
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Mayo Clinic
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Tiller
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Cardiff University
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Centre for Genetics Education, NSW Health
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Harmsen
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Healthwise
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Mayo Clinic
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Publication year or last update
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2004
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2005
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2011
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2011
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2019
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2003
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2007
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2012
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2017
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2017
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2017
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2017
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2019
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2019
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2008
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2014
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2017
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2018
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2019
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2019
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Origin
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NL
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USA
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USA
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USA
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USA
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USA
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Canada
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Australia
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GB
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GB
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Canada
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Australia
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USA
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USA
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Australia
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GB
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Australia
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NL
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USA
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USA
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BRCA1/2: BReast CAncer gene 1/2, BC: breast cancer, DA: decision aid, OC: ovarian cancer, MRI: magnetic resonance tomography, HRT: hormone replacement therapy, NSW: New South Wales, NICE: National Institute for Health and Care Excellence, grey field: full version of the DA not available
+: unlimited recommendation. (+): recommendation with limitation. ±: no clear recommendation possible, e.g., because of limited data. 0: no information. −: no recommendation. 1 – 26 See [Table 5].
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1 No precise details of disease history in the DA or no limitation of the target group.
2 In DA or corresponding primary study.
3
[7], [8], [9], [11]
4 Individual decision after detailed non-directive counselling.
5 S3 BC guideline, p. 62: Bilateral prophylactic mastectomy leads to a reduction in breast cancer incidence. “A reduction in breast cancer-specific mortality or overall mortality by bilateral prophylactic mastectomy has not been adequately confirmed.”
6 S3 BC guideline, p. 62: “Prophylactic bilateral salpingo-oophorectomy reduces the ovarian cancer risk by 97%. Whether the breast cancer risk is also reduced by this prophylactic operation has currently not been conclusively established.”
7 S3 BC guideline, p. 63: “A possible risk reduction by prophylactic administration of tamoxifen has not been clearly shown.”
8 S3 BC guideline, p. 64: Contralateral, secondary prophylactic mastectomy leads to a reduction in the contralateral cancer risk. “The prognosis of the first cancer should be considered when determining if contralateral secondary prophylactic mastectomy is indicated.”
9 S3 BC guideline, p. 64: Prophylactic adnexectomy leads to a reduction in breast cancer-specific mortality and to an increase in overall survival.
10 Recommendation in hormone receptor-positive sporadic breast cancer.
11 Postmenopausal women.
12 Recommendation for all women (with/without BRCA1/2 mutation).
13 Women > 35 years.
14 S3 OC guideline, p. 45: “Bilateral salpingectomy alone also has a risk-minimising but lower protective effect.”
15 S3 OC guideline, p. 45 – 46: “The operation leads to a reduction in the ovarian cancer risk by 34%. […] It has currently not been conclusively established whether the risk reduction can also be shown in BRCA1/2 mutation carriers.”
16 S3 OC guideline, p. 46: “A comprehensive meta-analysis, which included 28 studies, showed that obesity in adulthood was associated with an increased risk for ovarian cancer.” (Statement not specific for BRCA1/2 mutation carriers)
17 S3 OC guideline, p. 44: “It must be considered […] that ovariectomy of premenopausal women leads to an increase in the risk of myocardial infarction and osteoporosis-related fractures, among other things, so that short-term hormone therapy […]with a preventive aim also should be considered.”
18 No clear statement on BC screening.
19 Focus on BC prevention based on title of the DA or information from the authors on the DA. OC prevention options are sometimes cited also.
20 No clear differentiation between self- and medical examination.
21 Anastrozole for postmenopausal women in the ITO II study.
22 Example of details for 44-year-old premenopausal BRCA1 mutation carrier.
23 Recommendation especially for women under 50 years.
24 Focus on OC prevention based on title of the DA or information from the authors on the DA. BC prevention options are sometimes cited also.
25 Example of details for under 35-year-old BRCA1 mutation carrier without a history of BC.
26 Different DA for BRCA1 and BRCA2.
|
|
Target group
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Risk
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
|
|
|
X
|
|
|
|
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
X
|
X
|
|
X
|
X
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
X
|
X
|
|
X
|
|
|
Disease history
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
X
|
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
X
|
|
|
|
|
|
X
|
X
|
|
X
|
|
X
|
X
|
X
|
X
|
|
|
X
|
|
|
|
|
|
|
|
|
X
|
|
X
|
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
X
|
|
X
|
|
|
|
X
|
|
|
|
X
|
|
|
|
|
|
|
Individualisation of the information
|
|
|
|
|
|
|
|
|
X
|
|
X
|
|
|
|
|
|
X22
|
|
|
|
X25
|
|
X26
|
|
|
|
Treatment alternatives BC prevention
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Intensified screening
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
0
|
0
|
0
|
0
|
0
|
X
|
(X)18
|
|
|
X
|
X
|
X
|
(X)20
|
|
|
|
|
|
X
|
|
|
|
|
|
|
|
|
0
|
0
|
+
|
+
|
0
|
X
|
(X)18
|
|
|
X
|
X
|
X
|
(X)20
|
|
|
|
X
|
X
|
X
|
|
|
|
|
|
|
|
|
0
|
0
|
+
|
+
|
0
|
X
|
(X)18
|
|
|
|
|
|
X
|
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
0
|
0
|
+
|
+
|
0
|
X
|
(X)18
|
X
|
X
|
X
|
X
|
X
|
X
|
|
|
|
X
|
X
|
X
|
|
|
|
|
|
|
|
|
0
|
0
|
+
|
+
|
0
|
X
|
(X)18
|
X
|
X
|
X
|
|
X
|
X
|
|
|
|
X
|
X
|
X
|
|
|
|
|
|
|
|
Risk-reducing operations
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(+)4, 5
|
(+)8
|
(+)4
|
(+)4
|
0
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
|
|
X
|
X
|
X
|
X
|
|
|
|
|
|
X
|
|
|
±6
|
+9
|
0
|
0
|
0
|
|
|
X
|
|
|
|
X
|
|
|
|
|
X
|
X
|
|
|
|
|
X
|
|
|
|
|
0
|
0
|
0
|
0
|
0
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
0
|
0
|
0
|
0
|
0
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
X
|
|
|
|
|
|
X
|
|
Pharmacological prevention
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
0
|
0
|
(+)4, 11
|
0
|
0
|
|
X
|
|
|
X
|
X
|
|
|
|
X
|
|
|
X23
|
X
|
|
|
|
|
|
|
|
|
±7
|
(+)10
|
(+)4, 13
|
(+)11
|
0
|
X
|
X
|
X
|
|
X
|
X
|
X
|
|
X
|
X
|
X
|
X
|
X11
|
X
|
|
|
|
|
|
|
|
|
0
|
(+)10, 11
|
(+)4, 11
|
(+)11
|
0
|
|
|
|
|
|
|
|
X21
|
|
X
|
|
|
X11
|
X
|
|
|
|
|
|
|
|
Miscellaneous
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
0
|
+12
|
+12
|
+12
|
0
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
X
|
|
|
|
|
|
|
|
|
0
|
+12
|
(+)12
|
(+)12
|
0
|
|
|
|
|
|
|
|
X
|
|
|
|
|
|
X
|
|
|
|
|
|
|
|
|
0
|
+12
|
+12
|
+12
|
0
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
X
|
|
|
|
|
|
|
|
|
0
|
+12
|
+12
|
+12
|
0
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
0
|
+12
|
(+)12
|
(+)12
|
0
|
|
|
|
|
|
|
|
X
|
|
|
|
X
|
|
X
|
|
|
|
|
|
|
|
|
0
|
±12
|
0
|
0
|
0
|
|
|
|
|
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
0
|
+12
|
(+)12
|
(+)12
|
0
|
|
|
|
|
|
|
|
X
|
|
|
|
X
|
|
X
|
|
|
|
|
|
|
Table 4 Content of the decision aids: treatment alternatives for ovarian cancer prevention.
|
|
Recommendations in Germany3
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
S3 BC guideline, women without BC
|
S3 BC guideline, women without BC
|
S3 BC guideline, women without BC
|
S3 BC guideline, women without BC
|
S3 OC guideline
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Decision aids
|
With preventive measures regarding BC and OC
|
With preventive measures regarding BC19
|
With preventive measures regarding OC24
|
|
Developer
|
van Roosmalen
|
Armstrong
|
Culver
|
Kurian
|
Jabaley
|
Kaufman
|
Metcalfe
|
Centre for Genetics Education, NSW Health
|
NICE (premenopausal)
|
NICE (postmenopausal)
|
Metcalfe
|
Collins
|
Healthwise
|
Mayo Clinic
|
Tiller
|
Cardiff University
|
Centre for Genetics Education, NSW Health
|
Harmsen
|
Healthwise
|
Mayo Clinic
|
|
Publication year or last update
|
2004
|
2005
|
2011
|
2011
|
2019
|
2003
|
2007
|
2012
|
2017
|
2017
|
2017
|
2017
|
2019
|
2019
|
2008
|
2014
|
2017
|
2018
|
2019
|
2019
|
|
Origin
|
NL
|
USA
|
USA
|
USA
|
USA
|
USA
|
Canada
|
Australia
|
GB
|
GB
|
Canada
|
Australia
|
USA
|
USA
|
Australia
|
GB
|
Australia
|
NL
|
USA
|
USA
|
|
BRCA1/2: BReast CAncer gene 1/2, BC: breast cancer, DA: decision aid, OC: ovarian cancer, MRI: magnetic resonance tomography, HRT: hormone replacement therapy, NSW: New South Wales, NICE: National Institute for Health and Care Excellence, grey field: full version of the DA not available
+: unlimited recommendation. (+): recommendation with limitation. ±: no clear recommendation possible, e.g., because of limited data. 0: no information. −: no recommendation. 1 – 26 See [Table 5].
|
|
Target group
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Risk
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
|
|
|
X
|
|
|
|
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
X
|
X
|
|
X
|
X
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
X
|
X
|
|
X
|
|
|
Disease history
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
X
|
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
X
|
|
|
|
|
|
X
|
X
|
|
X
|
|
X
|
X
|
X
|
X
|
|
|
X
|
|
|
|
|
|
|
|
|
X
|
|
X
|
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
X
|
|
X
|
|
|
|
X
|
|
|
|
X
|
|
|
|
|
|
|
Individualisation of the information
|
|
|
|
|
|
|
|
|
X
|
|
X
|
|
|
|
|
|
X22
|
|
|
|
X25
|
|
X26
|
|
|
|
Treatment alternatives OC prevention
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Screening
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
0
|
0
|
0
|
0
|
–
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
0
|
0
|
0
|
0
|
–
|
X
|
|
X
|
|
X
|
X
|
|
|
|
|
|
|
|
|
X
|
|
|
|
X
|
X
|
|
|
0
|
0
|
0
|
0
|
–
|
X
|
|
X
|
|
X
|
X
|
|
|
|
|
|
|
|
|
X
|
|
|
|
X
|
X
|
|
Risk-reducing operations
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
+6
|
+6
|
+
|
(+)
|
+
|
|
|
X
|
X
|
X
|
|
X
|
|
|
|
X
|
X
|
X
|
|
X
|
X
|
X
|
X
|
|
X
|
|
|
0
|
0
|
0
|
0
|
(+)14
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
0
|
0
|
0
|
0
|
0
|
X
|
X
|
|
X
|
|
X
|
|
|
|
|
|
|
X
|
X
|
|
|
|
|
X
|
X
|
|
|
0
|
0
|
0
|
0
|
0
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
|
|
|
0
|
0
|
0
|
0
|
±15
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
X
|
|
|
|
|
|
0
|
0
|
0
|
0
|
0
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
X
|
|
|
X
|
|
Miscellaneous
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
0
|
0
|
0
|
0
|
0
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
|
|
|
|
|
|
0
|
0
|
0
|
0
|
+16
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
|
|
|
|
|
0
|
0
|
0
|
0
|
0
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
|
|
|
|
|
0
|
0
|
0
|
0
|
0
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
|
|
|
|
|
0
|
0
|
0
|
0
|
0
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
0
|
0
|
0
|
0
|
0
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
0
|
0
|
0
|
0
|
+
|
X
|
|
|
|
X
|
X
|
|
|
|
|
|
|
|
|
X
|
|
X
|
|
X
|
X
|
|
|
0
|
0
|
0
|
0
|
(+)17
|
|
X
|
|
|
|
|
|
|
|
|
|
|
X
|
|
X
|
X
|
X
|
X
|
|
X
|
Table 5 Content of the decision aids: information, instruments for supporting decision-making.
|
|
Recommendations in Germany3
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
S3 BC guideline, women without BC
|
S3 BC guideline, women without BC
|
S3 BC guideline, women without BC
|
S3 BC guideline, women without BC
|
S3 OC guideline
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Decision aids
|
With preventive measures regarding BC and OC
|
With preventive measures regarding BC19
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With preventive measures regarding OC24
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Developer
|
van Roosmalen
|
Armstrong
|
Culver
|
Kurian
|
Jabaley
|
Kaufman
|
Metcalfe
|
Centre for Genetics Education, NSW Health
|
NICE (premenopausal)
|
NICE (postmenopausal)
|
Metcalfe
|
Collins
|
Healthwise
|
Mayo Clinic
|
Tiller
|
Cardiff University
|
Centre for Genetics Education, NSW Health
|
Harmsen
|
Healthwise
|
Mayo Clinic
|
|
Publication year or last update
|
2004
|
2005
|
2011
|
2011
|
2019
|
2003
|
2007
|
2012
|
2017
|
2017
|
2017
|
2017
|
2019
|
2019
|
2008
|
2014
|
2017
|
2018
|
2019
|
2019
|
|
Origin
|
NL
|
USA
|
USA
|
USA
|
USA
|
USA
|
Canada
|
Australia
|
GB
|
GB
|
Canada
|
Australia
|
USA
|
USA
|
Australia
|
GB
|
Australia
|
NL
|
USA
|
USA
|
|
BRCA1/2: BReast CAncer gene 1/2, BC: breast cancer, DA: decision aid, OC: ovarian cancer, MRI: magnetic resonance tomography, HRT: hormone replacement therapy, NSW: New South Wales, NICE: National Institute for Health and Care Excellence, grey field: full version of the DA not available
+: unlimited recommendation. (+): recommendation with limitation. ±: no clear recommendation possible, e.g., because of limited data. 0: no information. −: no recommendation.
1 No precise details of disease history in the DA or no limitation of the target group. 2 In DA or corresponding primary study. 3
[7], [8], [9], [11]
4 Individual decision after detailed non-directive counselling. 5 S3 BC guideline, p. 62: Bilateral prophylactic mastectomy leads to a reduction in breast cancer incidence. “A reduction in breast cancer-specific mortality or overall mortality by bilateral prophylactic mastectomy has not been adequately confirmed.” 6 S3 BC guideline, p. 62: “Prophylactic bilateral salpingo-oophorectomy reduces the ovarian cancer risk by 97%. Whether the breast cancer risk is also reduced by this prophylactic operation has currently not been conclusively established.” 7 S3 BC guideline, p. 63: “A possible risk reduction by
prophylactic administration of tamoxifen has not been clearly shown.” 8 S3 BC guideline, p. 64: Contralateral, secondary prophylactic mastectomy leads to a reduction in the contralateral cancer risk. “The prognosis of the first cancer should be considered when determining if contralateral secondary prophylactic mastectomy is indicated.” 9 S3 BC guideline, p. 64: Prophylactic adnexectomy leads to a reduction in breast cancer-specific mortality and to an increase in overall survival. 10 Recommendation in hormone receptor-positive sporadic breast cancer. 11 Postmenopausal women. 12 Recommendation for all women (with/without BRCA1/2 mutation). 13 Women > 35 years. 14 S3 OC guideline, p. 45: “Bilateral salpingectomy alone also has a risk-minimising but lower protective effect.” 15 S3 OC guideline, p. 45 – 46: “The operation leads to a reduction in the ovarian
cancer risk by 34%. […] It has currently not been conclusively established whether the risk reduction can also be shown in BRCA1/2 mutation carriers.” 16 S3 OC guideline, p. 46: “A comprehensive meta-analysis, which included 28 studies, showed that obesity in adulthood was associated with an increased risk for ovarian cancer.” (Statement not specific for BRCA1/2 mutation carriers) 17 S3 OC guideline, p. 44: “It must be considered […] that ovariectomy of premenopausal women leads to an increase in the risk of myocardial infarction and osteoporosis-related fractures, among other things, so that short-term hormone therapy […]with a preventive aim also should be considered.” 18 No clear statement on BC screening. 19 Focus on BC prevention based on title of the DA or information from the authors on the DA. OC prevention options are sometimes cited also. 20 No clear differentiation between
self- and medical examination. 21 Anastrozole for postmenopausal women in the ITO II study. 22 Example of details for 44-year-old premenopausal BRCA1 mutation carrier. 23 Recommendation especially for women under 50 years. 24 Focus on OC prevention based on title of the DA or information from the authors on the DA. BC prevention options are sometimes cited also. 25 Example of details for under 35-year-old BRCA1 mutation carrier without a history of BC. 26 Different DA for BRCA1 and BRCA2.
|
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Target group
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|
Risk
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
|
|
|
X
|
|
|
|
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
X
|
X
|
|
X
|
X
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
X
|
X
|
|
X
|
|
|
Disease history
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
X
|
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
X
|
|
|
|
|
|
X
|
X
|
|
X
|
|
X
|
X
|
X
|
X
|
|
|
X
|
|
|
|
|
|
|
|
|
X
|
|
X
|
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
X
|
|
X
|
|
|
|
X
|
|
|
|
X
|
|
|
|
|
|
|
Individualisation of the information
|
|
|
|
|
|
|
|
|
X
|
|
X
|
|
|
|
|
|
X22
|
|
|
|
X25
|
|
X26
|
|
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|
Information
|
|
|
|
|
|
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|
|
|
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|
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|
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|
|
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|
|
|
|
|
|
|
|
BC/OC disease risks (text)
|
|
|
|
|
|
X
|
|
|
X
|
X
|
|
X
|
X
|
X
|
X
|
|
X
|
X
|
|
X
|
X
|
X
|
X
|
X
|
X
|
|
BC/OC disease risks (graphics)
|
|
|
|
|
|
|
|
|
X
|
X
|
|
X
|
|
X
|
X
|
|
X
|
X
|
|
|
X
|
X
|
X
|
X
|
|
|
Advantages/disadvantages of the preventive options
|
|
|
|
|
|
X
|
|
|
|
X
|
|
|
X
|
X
|
X
|
|
X
|
X
|
|
X
|
X
|
X
|
X
|
X
|
|
|
Experience reports
|
|
|
|
|
|
X
|
|
|
|
|
|
X
|
X
|
|
|
|
|
X
|
|
X
|
|
|
|
X
|
|
|
Instruments for supporting decision-making
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Step-by-step decision instructions
|
|
|
|
|
|
|
|
|
|
X
|
|
X
|
|
|
|
|
|
|
|
X
|
X
|
|
X
|
X
|
|
|
Personal weighting of advantages/
disadvantages
|
|
|
|
|
|
|
|
|
|
X
|
|
X
|
|
X
|
X
|
|
|
X
|
|
X
|
X
|
|
X
|
X
|
|
|
Note field (for own values, fears etc.)
|
|
|
|
|
|
X
|
|
|
|
X
|
|
|
X
|
X
|
X
|
|
|
X
|
|
X
|
X
|
|
|
X
|
|
|
List of questions to doctors/
counselling staff
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
|
|
|
|
|
|
|
X
|
|
|
X
|
|
Test of knowledge
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
X
|
|
|
Miscellaneous
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Addresses and/or internet links
|
|
|
|
|
|
|
|
|
|
X
|
|
X
|
X
|
|
|
|
|
|
|
X
|
X
|
X
|
|
|
|
|
References2
|
|
|
|
|
|
X
|
|
|
X
|
X
|
|
X
|
X
|
X
|
X
|
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
Four DAs offer those seeking advice the possibility of individualised information. This ranges from differentiating the mutation status (BRCA 1 or 2)
[34] to the possibility of individualising the information by means of detailed filter variables such as mutation status, age, menopause status and family history [32]. Thirteen of the 16 DAs contain instruments for decision-making, including the possibility of weighting advantages and disadvantages for oneself, step-by-step decision instructions and note fields for writing down thoughts, fears etc.
Quality
Sixteen of the 20 DAs were evaluated using the IPDASi v4.0 instrument ([Table 6]). Ten DAs (63%) met all qualification criteria and could be declared as DAs according to the IPDASi v4.0 definition [28], [32], [34], [35], [37], [38], [39], [40], [41], [44]. The other DAs were unable to meet one to two of the qualification criteria and therefore by definition do not count as DAs. For example, six of the DAs report insufficiently on how a decision impacts on further life, and two DAs do not adequately present the disadvantages of a decision option.
Table 6 Quality of the decision aids according to IPDASi v4.0 criteria [26].
|
|
DA with preventive measures regarding BC and OC
|
DA with preventive measures regarding BC
|
DA with preventive measures regarding OC
|
|
Publication
|
van Roosmalen (2004)
|
Kurian (2011)
|
Jabaley (2019)
|
Metcalfe (2007)
|
NSW Health (2012)
|
NICE, premenopausal (2017)
|
NICE, postmenopausal (2017)
|
Collins (2017)
|
Healthwise (2019)
|
Mayo Clinic (2019)
|
Tiller (2008)
|
Cardiff University (2014)
|
NSW Health (2017)
|
Harmsen (2018)
|
Healthwise (2019)
|
Mayo Clinic (2019)
|
|
Criteria
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
IPDASi: International Patient Decision Aid Standards instrument, BC: breast cancer, DA: decision aid, OC: ovarian cancer
|
|
Information
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Qualification criteria (5)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
|
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
|
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
|
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
|
|
+
|
–
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
–
|
|
Certification criteria (1)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
4
|
2
|
4
|
4
|
3
|
4
|
4
|
4
|
4
|
2
|
4
|
4
|
3
|
4
|
4
|
2
|
|
Quality criteria (2)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1
|
4
|
4
|
4
|
1
|
4
|
4
|
4
|
4
|
1
|
4
|
4
|
3
|
4
|
4
|
2
|
|
|
1
|
3
|
3
|
4
|
2
|
4
|
4
|
3
|
3
|
1
|
3
|
4
|
1
|
3
|
3
|
2
|
|
Probabilities
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Quality criteria (6)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
3
|
4
|
2
|
4
|
3
|
4
|
4
|
4
|
1
|
2
|
3
|
4
|
1
|
4
|
1
|
3
|
|
|
4
|
4
|
3
|
3
|
3
|
2
|
2
|
4
|
3
|
2
|
4
|
4
|
2
|
4
|
3
|
3
|
|
|
1
|
4
|
1
|
4
|
3
|
4
|
4
|
4
|
1
|
1
|
1
|
4
|
1
|
4
|
1
|
3
|
|
|
1
|
4
|
1
|
4
|
1
|
4
|
4
|
4
|
1
|
1
|
1
|
3
|
1
|
4
|
1
|
3
|
|
|
4
|
4
|
1
|
4
|
1
|
4
|
4
|
4
|
1
|
1
|
1
|
3
|
1
|
4
|
1
|
4
|
|
|
1
|
4
|
1
|
4
|
1
|
4
|
4
|
4
|
1
|
1
|
1
|
4
|
1
|
4
|
1
|
1
|
|
Values
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Qualification criteria (1)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
+
|
–
|
–
|
+
|
+
|
–
|
–
|
+
|
+
|
–
|
+
|
+
|
+
|
+
|
+
|
+
|
|
Quality criteria (1)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1
|
1
|
3
|
4
|
3
|
4
|
4
|
1
|
4
|
1
|
4
|
4
|
2
|
4
|
4
|
2
|
|
Support of decision-making
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Quality criteria (2)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1
|
4
|
1
|
4
|
1
|
2
|
1
|
1
|
4
|
1
|
4
|
4
|
1
|
4
|
4
|
1
|
|
|
1
|
1
|
3
|
4
|
4
|
3
|
3
|
1
|
4
|
1
|
4
|
4
|
2
|
4
|
4
|
4
|
|
Development process
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Quality criteria (6)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1
|
1
|
2
|
4
|
2
|
?
|
?
|
1
|
?
|
?
|
4
|
4
|
?
|
4
|
?
|
?
|
|
|
4
|
1
|
2
|
?
|
?
|
?
|
?
|
4
|
?
|
?
|
?
|
4
|
?
|
4
|
?
|
?
|
|
|
1
|
1
|
1
|
1
|
?
|
1
|
1
|
1
|
?
|
?
|
1
|
1
|
?
|
3
|
?
|
?
|
|
|
1
|
1
|
1
|
4
|
?
|
1
|
1
|
1
|
?
|
?
|
4
|
3
|
?
|
4
|
?
|
?
|
|
|
4
|
4
|
4
|
4
|
?
|
1
|
1
|
4
|
?
|
?
|
4
|
3
|
?
|
1
|
?
|
?
|
|
|
4
|
4
|
4
|
1
|
?
|
1
|
1
|
4
|
?
|
?
|
1
|
1
|
?
|
1
|
?
|
?
|
|
Evidence
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Certification criteria (4)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
2
|
4
|
4
|
|
|
1
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
|
|
1
|
2
|
2
|
3
|
2
|
1
|
1
|
1
|
1
|
1
|
2
|
3
|
1
|
2
|
2
|
1
|
|
|
1
|
1
|
1
|
4
|
1
|
1
|
1
|
1
|
1
|
1
|
1
|
1
|
1
|
4
|
1
|
1
|
|
Quality criteria (2)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1
|
3
|
2
|
4
|
1
|
2
|
2
|
1
|
1
|
1
|
4
|
1
|
1
|
3
|
1
|
1
|
|
|
1
|
1
|
2
|
4
|
1
|
2
|
2
|
1
|
1
|
1
|
1
|
1
|
1
|
3
|
1
|
1
|
|
Disclosure
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Certification criteria (1)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
4
|
4
|
4
|
4
|
4
|
1
|
1
|
4
|
1
|
1
|
4
|
4
|
1
|
4
|
1
|
1
|
|
Quality criteria (1)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1
|
2
|
2
|
4
|
4
|
1
|
1
|
1
|
4
|
1
|
4
|
2
|
2
|
4
|
4
|
1
|
|
Readability
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Quality criteria (1)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1
|
1
|
1
|
1
|
1
|
1
|
1
|
1
|
1
|
1
|
4
|
1
|
1
|
1
|
1
|
1
|
|
Evaluation
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Quality criteria (2)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
4
|
1
|
1
|
4
|
1
|
1
|
1
|
3
|
1
|
1
|
3
|
1
|
1
|
1
|
1
|
1
|
|
|
1
|
1
|
1
|
4
|
1
|
1
|
1
|
1
|
1
|
1
|
3
|
1
|
1
|
1
|
1
|
1
|
|
Qualification criteria (6)
|
6
|
4
|
5
|
6
|
6
|
5
|
5
|
6
|
6
|
5
|
6
|
6
|
6
|
6
|
6
|
5
|
|
Certification criteria (6)
|
2
|
3
|
4
|
6
|
4
|
3
|
3
|
4
|
3
|
2
|
4
|
5
|
3
|
4
|
3
|
2
|
|
Quality criteria (23)
|
7
|
10
|
7
|
19
|
6
|
9
|
9
|
12
|
7
|
0
|
12
|
15
|
1
|
18
|
7
|
6
|
The certification criteria are met fully by one DA (6%) [28]. The other DAs meet between two and five of the six criteria. The certification criteria most often reported as inadequate are updating of the DA, the degree of uncertainty of the information and the financing of the DA.
As regards the quality criteria, one DA meets 19 of the 23 criteria (82%) [28], whereas one DA meets none of the criteria [42].
Discussion
This study is the most up-to-date systematic review of DAs for BRCA1/2 mutation carriers. Despite an international consensus on quality criteria and evidence-based guidelines, the picture is heterogeneous regarding the content, form and quality of the analysed DAs. A recommendation or translation of international DAs for BRCA1/2 mutation carriers without prior examination cannot be made based on these results.
The assessed formal criteria included the target group and format. A precise definition of the target group is necessary as prevention and treatment recommendations differ depending on the genetic mutation and disease stage. For example, the recommendations on BC prevention in the German S3 and S2 guidelines vary depending on whether a BRCA1/2 mutation carrier does not have BC or has unilateral disease [7], [9]. Three of the DAs with statements on BC prevention do not differ in the definition of the target group with regard to BC disease history [37], [39], [42]. Five DAs address “Women with an increased OC risk” and also include women with Lynch syndrome as a target group as well as BRCA1/2 mutation carriers [38], [40], [41], [43], [44]. According to German guidelines, both groups should be advised with regard to risk-reducing (salpingo-)oophorectomy because of the increased OC risk, which is also done in the aforementioned DA, but further specific preventive measures are recommended to women with Lynch syndrome, including investigations such as colonoscopy, oesophago-gastro-duodenoscopy, transvaginal ultrasound and endometrial biopsy [8], [47]. Thirteen of 15 DAs have an online downloadable format. They can thereby be more readily individualised and updated. The 16 analysed DAs show large differences in content, both in the extent of the information provided in the text and in the treatment alternatives offered. Risk-reducing operations are mentioned in 14 of the 16 DAs. Here, the recommendations, apart from vagueness regarding the
difference between salpingo-oophorectomy and oophorectomy or contralateral and bilateral mastectomy, largely agree with the German guidelines [7], [8], [9]. There is similar agreement between the DAs and the recommendations in the German guidelines [9] on BC screening. The breast ultrasonography recommended in the guidelines is mentioned in only 3 of the 10 DAs in question. As regards pharmacological prevention as an option, there are no clear recommendations in the German guidelines ([Tables 3] to [5]), and the lack of clarity with this option is also reflected in the DAs; in one of the DAs in question, pharmacological prevention is not even listed [33], while all currently discussed options (raloxifene, tamoxifen, aromatase inhibitors) are mentioned in
three DAs [37], [42], [45]. A point of criticism is that screening for OC by CA-125 testing and/or transvaginal ultrasound is cited in seven DAs as a possible prevention option, including three DAs from 2019 [29], [40], [43]. The German S3 OC guideline [8] and international guidelines [48], [49] advise clearly against such screening.
Another critical point is that crucial contents are mentioned only briefly or not at all in a few DAs. For instance, in the Mayo Clinic DA on OC prevention, it is not mentioned that an immediate loss of fertility is associated with oophorectomy. As Kim et al. show, this knowledge cannot be assumed; in their study, published in 2014, on womenʼs knowledge about the subjects of oophorectomy and fertility, 38% of the BRCA1/2 mutation carriers stated that they did not know that a woman cannot have any more biological offspring when her ovaries have been removed [50].
The 16 DAs analysed differ very greatly in quality. Only ten met all IPDASi v4.0 qualification criteria, which, according to Joseph-Williams et al., define a tool as a DA thus: “Tools would not be considered a patient decision aid unless all of these criteria are met” [26]. The opposite conclusion means that six of the tools assessed here are not DAs according to the IPDAS Collaboration. It is problematic that nearly all these tools call themselves DAs ([Table 2]). The IPDASi v4.0 certification criteria are met fully only in the DA of Metcalfe et al. [28], which was developed following the quality criteria of the IPDAS Collaboration. In the case of all other tools, decision bias due to the DA cannot be excluded. It is particularly difficult when the certification criterion of balanced representation is not met. For instance, in the Mayo Clinic tool for BC prevention, the
possibility of risk-reducing mastectomy including the advantages, disadvantages and risks is explained in detail but, by contrast, BC screening is mentioned in only one sentence. A weakness of this study is that a DA in Chinese had to be excluded because of the lack of capacity to translate this. In addition, a recent DA could be included but qualitative analysis was not possible as a full version was not obtained from the authors.
The strengths of this study are the clear search protocol, the inclusion of five different databases, no limitations of the design of the primary studies or format of the DAs, as well as assessment of the DAs by three independent reviewers. The quality of the DAs was examined using the IPDAS collaboration tool, which allows a detailed analysis of DAs and meets the current international standard in DA quality assessment.
This study has the following implications for practice: BRCA1/2 mutation carriers should be managed with evidence-based and high-quality DAs in counselling centres since
-
Unlike pure patient information leaflets, DAs also include clarification of the patientʼs own values and preferences,
-
Those seeking advice are protected from incorrect information due to poor-quality decision tools.
The development of DAs should be guided by the quality criteria of the IPDAS collaboration and precise target group definition and various formats (printed version, App) should be provided.
Conclusion
To date there is still no DA for BRCA1/2 mutation carriers for German-speaking countries that is used routinely in clinical practice. Various support tools for BRCA1/2 mutation carriers are currently in development or clinical testing, however, including two DAs [23], [51], [52], [53]. In developing a German DA, already existing international DAs can serve formally as a basis and the content regarding treatment recommendations must be adapted to the German guidelines. To ensure high DA quality, it is crucial to follow the quality criteria of IPDAS Collaboration when developing it.
Supplementary Material
Appendix 1: Search strategy for each database
