Background and rationale {6a}
Women with a pathogenic germline mutation in the
BRCA1 or
BRCA2 gene face a high risk of developing breast cancer (BC) and ovarian cancer (OC). The average cumulative life-time risk for BC increases with age [
1,
2], reaching about 70% by the age of 80 [
1]. The average cumulative lifetime risk for OC is around 44% (
BRCA1 mutation) and 17% (
BRCA2 mutation) [
1]. Compared to women affected by sporadic BC or OC,
BRCA1/2 mutation carriers without a history of cancer, in the following referred to as ‘previvors’ [
3], develop BC or OC about 20 years earlier in their life. Those with a history of unilateral BC, in the following referred to as ‘survivors’ [
4], face an average cumulative 20- to 25-year risk of contralateral BC of about 40 to 44% (
BRCA1 mutation) or around 26 to 33.5% (
BRCA2 mutation) [
1,
5].
Newly diagnosed
BRCA1/2 mutation carriers are offered various preventive options to counter their increased cancer risks. These include an intensified breast cancer screening programme for previvors or an intensified breast cancer screening and aftercare programme for survivors and risk-reducing surgeries of the breasts and the adnexa for both groups. Intensified breast cancer screening (breast magnetic resonance imaging (MRI), breast ultrasound and mammography) enables BC to be detected at an early, potentially curable stage in 85% of cases [
6], but does not reduce the risk of developing BC. Women who opt for screening in the first place can postpone their final decision to have surgery. Due to the limited specificity of the MRI, screening often yields false-positive results [
6] which can lead to further often more invasive diagnostic tests (e.g. re-imaging or breast biopsies) which may later prove unnecessary and may trigger transient anxiety in women [
7]. In contrast, risk-reducing bilateral mastectomy significantly decreases the risk of developing BC [
8] for previvors and provides a survival benefit to
BRCA1 mutation carriers [
9]. Risk-reducing contralateral mastectomy lowers the risk of contralateral BC and reduces overall mortality in survivors [
10]. However, removal of the breasts is an irreversible decision that affects physical integrity and requires further decisions, e.g. which form of surgery or whether and, if so, which breast reconstruction the woman would prefer. For survivors, the decision-making process may be even more complex because they may face competing risks (e.g. risk of BC recurrence on the affected side) that may have to be weighed against the benefits of risk-reducing surgery on the non-affected side.
In the absence of an effective screening method for the adnexa [
11‐
14], the only preventive option to counter the risk of OC is risk-reducing bilateral salpingo-oophorectomy. It reduces both the risk of OC [
15] and the overall and OC specific mortality [
16]. However, consequences include the definite loss of fertility and possible premature menopause; the latter can cause menopausal symptoms such as hot flashes, as well as long-term consequences such as cardiovascular disease and osteoporosis [
17].
Each preventive option is accompanied with distinct advantages and disadvantages that each mutation carrier will judge and weigh individually depending on her personal experiences, values and preferences. The same applies to the several options of breast reconstructions after mastectomy, to family planning or to steps to be taken to treat undesired effects of an option [
18]. For example, to counter the negative consequences of surgical menopause after a risk-reducing bilateral salpingo-oophorectomy, temporary hormone replacement therapy might be considered for premenopausal women [
11]. Hence,
BRCA1/2 mutation carriers face several so-called preference-sensitive decisions [
19,
20]. These can lead to considerable decisional conflicts that can be associated with delays of decisions, dissatisfaction, decision regret or blaming of healthcare providers [
21‐
26]. These negative consequences might be further complicated by lacking knowledge and understanding of the individual risk constellation and available options or by personal stressors and psychosocial, family and/or psychological factors [
20,
26‐
29].
In order to support
BRCA1/2 mutation carriers during their complex decision-making process in choosing a preventive option and the right time to do so, a number of supportive tools, in particular, decision aids (DAs), have been developed internationally [
30‐
36]. A systematic review on DAs for women with
BRCA1/2 mutations identified four RCTs and one pretest-post-test study that assessed the effectiveness of DAs on decision-, knowledge- and health-related criteria. The analysis showed that DAs support these women most likely by improving decision-related outcomes: Women who received a DA experienced lower decisional conflict were more likely to come to a decision and were more satisfied with the decision made compared to women who did not receive a DA [
37]. Favourable effects of DAs on decision-related factors as well as on knowledge are reported by a previous Cochrane Review that analysed 105 RCTs involving a total of 31,043 participants with regard to the effects of DAs on patients facing treatment or screening decisions across different indications. High-quality evidence was found for the following effects: DAs improve knowledge about the available options, lower decisional conflicts resulting from the feeling of not being informed and support clarification of values and preferences of the addressees [
38].
In Germany, following receipt of the genetic test result, women with a pathogenic
BRCA1/2 mutation receive personalised counselling from a medical specialist at one of the specialised GC-HBOC centres or their affiliated breast centres. The post-test genetic counselling and care concept (in the following referred to as ‘standard care’) includes detailed non-directive information on the women’s mutation status, their individual risk prediction, risks and benefits of the available risk-adapted prevention options and their consequences [
11,
39‐
41], provision of written information, e.g. on self-help or psychological support options, along with a physician’s letter summarising the contents of the consultation. So far, no additional structured intervention is used to provide women carrying
BRCA1/2 mutations with targeted support for making high-quality decisions defined as being informed by the best available scientific knowledge and based on the women’s values and preferences [
42,
43].
For this reason, two evidence-based DAs (one for previvors (DA-A), one for survivors (DA-B) with
BRCA1/2 mutations) that correspond to the evidence-based guidelines and consented procedures in the German healthcare system were developed in an upstream research process [
44]. The development of the DAs followed a structured, quality-controlled procedure according to the International Patient Decision Aid Standards Collaboration [
45‐
47]. Both DAs follow the same structure and share the same content for all aspects that are valid for both target groups (e.g. information on genetic mutations, methods of breast cancer screening). Yet, they differ in aspects where the respective target group needs and/or wishes distinct information. For example, previvors need information on the risk-reducing bilateral removal of healthy breasts, while survivors need information on BC in the affected breast and on the risk-reducing removal of the non-affected breast. Before the newly developed DAs can be incorporated into standard care, it is required to evaluate these in terms of their effectiveness and acceptability in clinical use [
45,
48]. In order to fulfil this final quality criterion, the DAs will be evaluated in the randomised controlled trial (RCT) described here in detail.