A systematic review of psycho‐social interventions for individuals with a BRCA1/2 pathogenic variant

1 INTRODUCTION

Women that carry a BRCA1/2 pathogenic variant are at a significantly increased risk of developing certain cancers in their lifetime. The cumulative lifetime risk of breast cancer ranges between 40% - 87% for women with a BRCA1 pathogenic variant, and an ovarian cancer risk of 16% – 68% (Kuchenbaecker et al., 2017). There is similar risk for women with a BRCA2 pathogenic variant, with a 27% – 84% lifetime breast cancer risk, and 11% – 30% ovarian cancer risk (Kuchenbaecker et al., 2017). To reduce these cancer risks, it is advised that women undergo risk-reducing measures, of which the most common are surgical, namely prophylactic double mastectomies, and prophylactic salpingo-oopherectomies, usually commencing between the ages of 30 – 40. Pharmacological methods are also available, specifically chemoprevention for breast cancer risk reduction, and the oral contraceptive pills for reducing ovarian cancer risk (Bermejo-Pérez et al., 2007; Friebel et al., 2014).

At present, there is contradicting literature detailing the psychological coping trajectory experienced by BRCA1/2 pathogenic variant carriers. Past meta-analytic research noted that the distress experienced by this population did not reduce exponentially, and rather there was a limited natural decrease in levels of distress over time (Meiser & Halliday, 2002). A more recent meta-analysis (Hamilton et al., 2009) concluded that while rates of distress and anxiety did increase in the timeframe immediately post-test results (0–4 weeks), these returned to baseline levels after a moderate (5–24 weeks) or long (25–52 weeks) period. Hamilton et al., (2009) further discuss that while levels did return to baseline after some time, baseline levels of cancer-specific distress were higher than that of the general population. This was not the case for anxiety, with levels being similar to general population rates.

Furthermore, little research has been conducted on the differing intervention methods that target psycho-social well-being in this population. A recent Cochrane systematic review did assess this, however, it focused only on the time frame following prophylactic salpingo-oopherectomy (Jeffers et al., 2017). The current systematic review is the first to assess interventions that emphasize psychological, behavioral, or social factors rather than physiological factors in a BRCA1/2 pathogenic variant population, that aim to promote adjustment and improve psychological outcomes. Adjustment is defined in terms of alleviating stress, anxiety, depression and distress, and enhancing coping and knowledge of risk perceptions in those with a known BRCA1/2 pathogenic variant. This review assessed these, with input from the target population, and further evaluation of theory use, detailed below.

1.1 Patient and public involvement

It is broadly agreed upon that addition of Patient and Public Involvement (PPI) can help improve the impact and relevance of studies in fields such as health research (Pollock et al., 2018). The inclusion of stakeholders of the target population under study can assist in bridging the research–implementation gap through the co-creation of knowledge between the researcher and those being researched (Heaton et al., 2015; Pollock et al., 2018). Given the frequency with which systematic reviews are utilized to inform both research plans and policy change, it is paramount that the views of the population at hand are at the forefront of research design. This review incorporated the involvement of a PPI panel who provided input on the communication and dissemination of review findings.

1.2 Theory use

In prior psycho-oncology research, the use of theory in interventions has been associated with improved intervention effectiveness (Bluethmann et al., 2017). There has been no investigation into the use of theory in intervention development and design in this field as of yet. Therefore, the current review, through use of a behavioral science tool — The Theory Coding Scheme (TCS; Michie & Prestwich, 2010), assesses whether there were any theoretical underpinnings in the included studies. The TCS is a mechanism providing a means through which the theoretical structure of interventions can be assessed, and has been previously highlighted as a tool which can be employed in an evidence synthesis methodology (Michie & Prestwich, 2010).

This review will aim to explore the current available evidence to synthesize the various interventions aimed at improving psychological adjustment in individuals with a BRCA1 or BRCA2 pathogenic genetic variant, with a secondary aim of summarizing the theories utilized in intervention design.

2 METHODS

A protocol for the systematic review was registered on PROSPERO (see: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=139546). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (Moher et al., 2009) were used to inform the review procedure and reporting (see Appendix SA).

2.1 Eligibility criteria

Studies were included if they were psychological or psycho-social interventions aimed at improving psychological adjustment in individuals with a pathogenic variant in BRCA1/2. Studies were required to include adult participants (>18 years) post-genetic testing — participants must have been aware of their BRCA1/2 pathogenic variant carrier status prior to intervention commencement. A restriction of papers published in English after 1990 (when the BRCA1/2 gene was discovered to be relevant in hereditary cancers) was applied. Studies that sampled individuals prior to their pathogenic variant result were excluded. Only experimental studies (randomized controlled trials) and quasi-experimental studies were included in this review. Papers were included that assessed one or more psychological or psycho-social variable (e.g., distress, quality of life, and anxiety) as an outcome.

2.2 Search Strategy

An OVID Medline search strategy (see Appendix SB) was compiled by NW, and was checked and revised by an expert research support librarian before translating into specific search strategies for each database. The search strategy was based on two main concepts; hereditary breast and ovarian cancer terms related to BRCA1/2, and terms related to psychological adjustment, distress, and quality of life. The following electronic databases were searched OVID (MEDLINE(R), PsycINFO, PsycExtra, Access PsycARTICLES, Journals @ Ovid Full Text, Your Journals @ Ovid), EBSCO (CINAHL, Psychology and Behavioral Science Collection), Cochrane Library, PubMed, Web of Science Core Collections, and Scopus. Forward citation searches (screening articles that have cited any of the included articles) and backward citation searches (screening the reference list of included papers) were conducted on all articles that were included after full-text screening. Conference abstracts for the following sources from 1990 onward were also searched: Irish Society of Human Genetics and European Society of Human Genetics.

2.3 Assessment of study eligibility

Duplicates were removed using EndNote X8. Searches were then uploaded to Rayyan QCRI (Ouzzani et al., 2016), an open-source website designed for screening papers for systematic reviews, wherein a second screening for duplicates was conducted. All further screening was then conducted utilizing the Rayyan QCRI software to allow for independent screening of papers.

A single reviewer (NW) initially screened titles to remove papers that were deemed irrelevant (e.g., those with a complete medical/pharmaceutical focus). Abstract screening followed, whereby two reviewers (NW and SM) worked independently on screening all remaining abstracts, categorizing them as ‘include’, ‘exclude’, or ‘unsure’. Full texts of those classified as ‘include’ and ‘unsure’ were then screened and assessed for eligibility in duplicate (NW and SM). Disagreements were resolved through discussion between the two reviewers, and a third reviewer (AMG) resolved any differences.

2.4 Data extraction

The following data were extracted for each paper by two reviewers (NW and SM) using a standardized data extraction form on Microsoft Excel: author/year published/country of publication/language, journal citation, study design/methodology/setting, study population (sample size, participant characteristics, age/gender/ethnicity/socio-economic status/education/parity, cancer diagnosis; yes or no, BRCA1 or BRCA2 pathogenic variant identified), intervention details, type of intervention, mode of delivery, who delivered, intervention duration/number of sessions, and outcomes (measures used to assess outcomes, how the outcome was defined). Disagreements between NW and SM were resolved by discussion or by getting input from a third reviewer (AMG).

2.5 Synthesis

A meta-analysis was not deemed to be appropriate due to the small number of included studies, in which there was minimal homogeneity in design or outcome. Data are therefore presented in a narrative synthesis, following the approach proposed by Popay et al., (2006).

2.6 Risk of bias assessment

Risk of bias was independently assessed by two reviewers (NW and SR). The included randomized controlled trials (n = 9) were assessed utilizing The Cochrane Risk of Bias Tool (Sterne et al., 2019), and the non-randomized controlled trials (n = 6) were assessed using Cochrane's Risk Of Bias In Non-randomized Studies – of Interventions (ROBINS-I) tool (Sterne et al., 2016).

2.7 Theory coding assessment

The use of theory in included interventions was assessed using the Theory Coding Scheme, a reliable method for assessing the extent to which behavioral interventions are theory-based (Michie & Prestwich, 2010). In line with a previous systematic review of interventions (Hennessy et al., 2019), items 11–19 of this scheme were utilized, as these focus on the extent to which the design of an intervention was based on theory. NW and SM carried out the assessment, with input from AMG to resolve any disagreements.

2.8 Public and patient involvement (PPI)

A PPI panel of six individuals with a BRCA1/2 pathogenic variant provided input on the dissemination of the review outside of academic journals to reach relevant patient groups. This group advised on how to disseminate the research outside of academic journals, informing on what they would find relevant and interesting from the review, and where they would go to find such information. Demographics of the panel are presented in Table S1. In addition, another group of eight women participated in a once-off consultation, hosted by the Irish Association for Cancer Research; the ‘Patient's Voice in Cancer Research—Dragon's Den’ event in February 2020. The participants at the Dragon's Den event were consulted broadly on the issue around language used in reporting on the BRCA1/2 population.

3 RESULTS 3.1 Search results

Database searches and hand searches were completed on the 19th of September 2019. A total of 1,024 results were retrieved, 365 were duplicates, and 659 papers were screened at title and abstract stage, following which 383 papers were excluded. Finally, 176 full-text papers were screened. Thirteen papers were included and were forward and backward searched to screen for any further potentially relevant publications. Two additional papers were identified—resulting in a total of fifteen studies. All included studies were published between 2004 and 2019. Details of screening and reasons for exclusion are presented in a PRISMA flow chart (Moher et al., 2009; see Figure S1).

3.2 Risk of bias summary 3.2.1 Cochrane risk of bias

As shown in Figure S2, four studies (Hooker et al., 2011; Kiechle et al., 2017; Landau et al., 2015; van Roosmalen et al., 2004) were rated as being at high risk of bias, with five (van Driel et al., 2019; Graves et al., 2010; Metcalfe et al., 2017; Visser et al., 2016; White et al., 2014) being rated at moderate risk. No studies were considered to be at low risk of bias.

3.2.2 ROBINS-I

As shown in Figure S3, four studies (Esplen et al., 2004; Landsbergen et al., 2010; Listøl et al., 2017; K. Metcalfe et al., 2007) were rated as being at moderate risk of bias, with one rated at serious risk (Bober et al., 2015). One study was considered to be at critical risk of bias (Kwiatkowski et al., 2019).

3.3 Study design

Nine studies (60%) were randomized controlled trials, the remaining six (40%) were non-randomized studies. The included interventions were predominantly longitudinal, with only two studies utilizing a pre-post design (Landsbergen et al., 2010; Metcalfe et al., 2007). The range of follow-up times for these studies extended between immediately post-intervention (zero weeks) to 12-month post-intervention. Two studies tracked participants at just two weeks before, and two weeks after the intervention (Esplen et al., 2004; Listøl et al., 2017). One of these intervention programs lasted over one year (Esplen et al., 2004), whereas the other was a short-term study, comprised of a single group-based session (Listøl et al., 2017). The remaining studies followed participants across a series of time points, ranging between a total of two months to 12 months. Overall, the mean follow-up time in these studies was six and a half months. Detailed information on this is displayed in Table S2, with a note of any significant changes in reported outcomes for each study time point.

3.4 Study populations

The populations in these studies were quite homogenous. Table 1 denotes the characteristics of the population that were reported in these studies. All studies reported exclusively female participants, and none differentiated between BRCA1 or BRCA2 pathogenic variants, reporting upon it as a dichotomous (yes/no) variable, indicating whether a person did or did not harbor a pathogenic variant. Sample size in these ranged from seven to 214, with a total sample of 1,340 across all studies, with an average of 89 participants per intervention. The mean age of participants in 13 studies ranged between 26.40 and 49.63 years. One study assessed age by denoting the number of people either above or below 50 (Graves et al., 2010), while another did not include information on the age of included participants (Landsbergen et al., 2010). There were limited data reporting on ethnicity/race in the studies, with only three (20%) recording such information, noting any demographic other than white, with just one specifically indicating participation of individuals from Ashkenazi Jewish heritage (7%). Most studies (60%) reported that some participants had undergone at least one preventative measure. There were reports of cancer diagnosis in the majority of studies, with 13 (87%) presenting data on breast cancer, 12 (80%) on ovarian, and five (33%) studies taking a broader approach and reporting on the presence of a diagnosis of any cancer type. No studies specifically investigated other carcinomas that are often associated with a BRCA1/2 pathogenic variant, such as pancreatic cancer.

TABLE 1. Description of population characteristics reported in studies Study Population characteristics No. (%) of Studies Ethnicity White 3 (20) Hispanic 1 (7) Not reported 12 (80) Types of Cancer Present in Population Breast 13 (87) Ovarian 12 (80) Any 5 (33) Prophylactic Surgery Mastectomy (single or bilateral) 8 (53) Salpingo-oopherectomy 7 (47) None taken 4 (27) Children Yes 8 (53) 3.5 Narrative synthesis

The included studies aimed to improve psychological functioning (e.g., anxiety and depression) through some form of intervention, although often this was not the primary objective of the study. Many provided educational content or elements of group support to their participants. Table 2 displays the components of included study characteristics.

TABLE 2. Table of intervention components for the 15 studies Bober Driel Esplen Graves Hooker Kiechle Kwiatkowski Landau Landsbergen Listøl Metcalfe Metcalfe Roosmalen Visser White Peer Support X

Educational:

Management Strategies

X X X X

Educational:

Psychological Health

X X X X X

Educational:

Physical Health

X X X X X X X X X

Educational:

Hereditary Risk

X X

X

Tailored

X X X X

Educational:

Other

X

Sexual Wellbeing

X

Social Domains

Relaxation/Stress

Reduction Training

X X X Exercise X Group Setting X X X X X CBT X Decision Aid X X X Telephone Counseling X X X Mindfulness X X 3.6 Intervention design

Many studies assessed how knowledge and decisional conflict were influenced by information provision, rather than focusing on the psychological aspects of participation in an intervention. Table 2 presents the different aspects of the included interventions, to provide a visualization of the intersection and differences between the varied approaches. There was some overlap with approach, namely that the majority, 13 (87%) studies, utilized some form of education in their method. While an effort is made to remain consistent with what corresponds to providing ‘education’, it is often unclear what researchers considered educational, and what the distinguishable foci of these were (e.g., physical health and hereditary risk). Other than educational elements, there was minimal further homogeneity within study design. Further details on study characteristics are presented in Table S3.

3.7 Psychological outcomes

All studies utilized at least one measure of psychological adjustment. There was significant variation in the measures used to assess different elements of psychological adjustment, the details of these are presented in Table 3. This variation may have been a consequence of questionnaires being specifically created for the given paper, as was the case in nine (60%) of the included studies, rather than utilizing pre-validated measures.

TABLE 3. Psychological variables assessed in the 15 studies General Distress Anxiety Stress Depression Quality of Life Cancer-Specific Distress Genetic Testing Specific Distress Other Bober et al., (2015) X Driel et al., (2019) X X X Esplen et al., (2004) X X X X Grief Graves et al., (2010) X X X X Hooker et al., (2011) X X X Kiechle et al., (2017) X X Kwiatkowski et al., (2019) X X

Self-Esteem

Hope

Landau et al., (2015) X Cancer Worry Landsbergen et al., (2010) X Mood Listøl et al., (2017) X X Threatening Medical Situation Metcalfe et al., (2007) X Metcalfe et al., (2017)

留言 (0)

沒有登入
gif