Abstract
Hereditary breast and ovarian cancer caused by a BRCA1/2 mutation is the most frequent indication for preimplantation genetic diagnosis (PGD) in the Netherlands. The extent to which involved professionals are informed about this option, however, is unclear. The few available international studies mostly represent a limited range of professionals, and suggest that their knowledge about PGD for hereditary cancer syndromes is sparse and referral for PGD is based on limited understanding. A cross-sectional survey assessing awareness, knowledge, acceptability and PGD-referral for BRCA was completed by 188 professionals involved in the field of breast and ovarian cancer or reproduction. One-half of professionals were aware of PGD for BRCA, and most had a low to moderate level of knowledge. A total of 86% considered PGD for BRCA acceptable and 48% had referred patients with BRCA for PGD. Awareness and knowledge was higher among professionals who worked at a university hospital (compared with a general hospital). Knowledge of PGD was positively associated with discussing and referring for PGD, and PGD acceptability was associated with previous awareness. Although PGD counselling is the primary responsibility of the geneticist, other involved professionals may be gatekeepers as patients rely on them for raising awareness and referral.
Keywords
Introduction
About 5–10% of all cancers are caused by a hereditary predisposition (
Garber, Offit, 2005
). Women with a BRCA1/2 mutation face an elevated risk of 27–57% of developing breast cancer and 6–40% of developing ovarian cancer by the age of 70 years (Brohet et al, 2014
, - Brohet R.M.
- Velthuizen M.E.
- Hogervorst F.B.
- Meijers-Heijboer H.E.
- Seynaeve C.
- Collée M.J.
- Verhoef S.
- Ausems M.G.
- Hoogerbrugge N.
- van Asperen C.J.
- Gomez Carcia E.
- Menko F.
- Oosterwijk J.C.
- Devilee P.
- van 't Veer L.J.
- van Leeuwen F.E.
- Easton D.F.
- Rookus M.A.
- Antoniou A.C.
HEBON Resource
Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations.
Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations.
J. Med. Genet. 2014; 51: 98-107
Chen, Parmigiani, 2007
). Preventive possibilities are limited to chemoprevention and prophylactic surgery, which can be both physically and psychologically demanding. Although therapeutic options are available, hereditary breast and ovarian cancer (HBOC) caused by a BRCA1/2 mutation accounts for a disproportionally large amount of life years lost as it occurs at a relatively young age (Roukos, Briasoulis, 2007
). As this is an autosomal dominant predisposition, there is a 50% risk of passing it on to the next generation. In the Netherlands, couples with a BRCA1/2 mutation and a wish for a biological child have three reproductive options: a natural pregnancy, implying acceptance of the risk of passing on the BRCA mutation; prenatal diagnosis (diagnosis during pregnancy and possible termination of pregnancy in case of a female carrier); and preimplantation genetic diagnosis (PGD) (selection of IVF and intracytoplasmic sperm injection [ICSI] embryos, free of the BRCA mutation before implantation in the uterus).As use of PGD was permitted for late-onset genetic cancer syndromes in the Netherlands in 2008, HBOC caused by a BRCA1/2 mutation has been the most frequent indication for PGD, with 25 couples that started a PGD treatment for BRCA in 2013, 36 couples in 2014 and 45 couples in 2015 (
PGD Netherlands, 0000
). Ethical concerns about PGD for late-onset cancer syndromes such as BRCA have risen internationally among patients and professionals owing to the condition's adult onset character, incomplete penetrance and availability of (albeit physically and emotionally traumatic) preventive and therapeutic options (- PGD Netherlands
Year reports 2013, 2014, 2015.
https://www.pgdnederland.nl/jaarverslagen
Date accessed: May , 2017
Julian-Reynier et al, 2009
, Klitzman et al, 2013
, Rich et al, 2014
).Although PGD is nowadays available as a reproductive option for couples with BRCA in many countries, published data show that knowledge among involved health professionals is sparse and most would refer for PGD based on limited understanding of the procedure and its applications (
Abbate et al, 2014
, Caldas et al, 2010
; Klitzman et al, 2013
). Moreover, professionals' intentions to refer eligible patients for PGD counselling often exceed their actual referral behaviour (Brandt et al, 2010
, Klitzman et al, 2013
). The few available studies focusing specifically on hereditary cancer syndromes (Brandt et al, 2010
, Julian-Reynier et al, 2009
, Quinn et al, 2014
) show that professionals' acceptability of PGD is often influenced by the nature of the predisposition and the patient's personal history of cancer. The previously mentioned studies focused on various outcomes, such as assessing PGD knowledge by awareness or measuring acceptability of PGD depending on patients' family history of cancer and reproductive history among gynaecologists, gynaecological oncologists, obstetricians or oncology nurses; only one study included clinical geneticists, the specialists who are primarily involved in PGD (Julian-Reynier et al, 2009
). Therefore, we assessed awareness, knowledge and acceptability of PGD for BRCA among health professionals, and their referral behaviour (including clinical geneticists and genetic counsellors), and investigated possible associations of these outcomes with clinical and demographic factors. This study was carried out as part of an overarching project aimed at enhancing guidance and psychological support for couples with BRCA and a child wish in the Netherlands.Materials and methods
Participants and procedures
Participants were recruited in collaboration with the following Dutch associations of health professionals that are involved in the field of hereditary breast and ovarian cancer, reproduction, or both: The Association of Clinical Genetics Netherlands (VKGN), The Dutch Association of Genetic Counsellors (NVGC), The Dutch Association for Obstetrics and Gynaecology (NVOG), and The Dutch Association for Oncology (NvVO). The associations sent one mass mail inviting their members to participate in the study. No reminders were sent. The approached professionals were gynaecologists, clinical geneticists, genetic counsellors, medical oncologists and fertility physicians. The single inclusion criterion was being a medical specialist involved in the field of reproduction, oncology, or both, whereas the single exclusion criterion was insufficient understanding of the Dutch language as the survey was in Dutch. The email invitation contained brief information about the study, contact details of the researcher and a link to the online questionnaire. It was clearly stated that participants gave their informed consent by initiating the questionnaire. Procedures were approved by the Medical Ethics Committee of the Maastricht UMC+, reference number: METC 12-4-075, dd 18-06-2012.
Questionnaire
To explore an appropriate basis for the questionnaire content and to ensure relevance of the questions for the approached professional groups, seven in-depth telephone interviews were conducted with several medical professionals (two clinical geneticists, two genetic counsellors, one gynaecologist, one gynaecologic oncologist and one medical oncologist) before the start of the study. The duration of these interviews was about 30 mins, and they addressed awareness, knowledge, attitude, referral behaviour and informational needs of PGD for BRCA. The interviews were audio taped, transcribed verbatim and analysed. On the basis of these interview data and available published data, a cross-sectional survey was developed. The survey was pilot tested by a clinical geneticist, a gynaecologist and a medical oncologist, and revised accordingly before circulation.
The four main outcome variables were as follows: awareness of the possibility of PGD for BRCA; the level of knowledge about PGD (in general and specifically for BRCA); acceptability of PGD for BRCA; and referral behaviour in relation to PGD for BRCA. Knowledge was assessed by two scales: the first scale consisted of 16 (categories of) medical indications, and measured knowledge of the conditions for which PGD is legally permitted in the Netherlands (of which 14 are permitted and two are not permitted), with a minimum score of 0 and a maximum score of 16. In this context, ‘legally permitted’ does not merely mean that it is reimbursed by government insurance; PGD for other conditions can be considered illegal in the Netherlands at the time of data-collection, even when paid for privately. On this scale, adjusted for the probability of guessing a correct answer (50% per question), we defined a score of 0–8 as low, 9–12 as moderate and 13–16 as a high level of knowledge. The second knowledge scale consisted of 15 closed-ended questions (true/false/not sure) about the procedure of, and eligibility for, a PGD treatment in general (including three items specifically for BRCA), with a minimum score of 0 and a maximum score of 15. On this scale, similarly adjusted for the probability of guessing a correct answer (50% per question), we defined a score of 0–8 as low, 9–12 as moderate and 13–15 as a high level of knowledge. Acceptability of PGD for BRCA was measured with an ordinal scale (1 = totally disagree to 5 = totally agree), as were referral behaviour and the intention to refer for PGD for BRCA (1 = no definitely not to 5 = yes, definitely). We additionally asked participants whether they thought acceptability of PGD for BRCA should depend on the couple's personal or family history of cancer and if it should be the couple's autonomous decision whether PGD is acceptable (and therefore allowed) for them (both items: 1 = totally disagree to 5 = totally agree). The main questionnaire items are presented in Table 1. Demographic factors recorded were age, gender, partner status (partner/no partner), religiosity (yes/no), ethnicity (native Dutch/non-native) and children (yes/no). Partner status and having children were assessed as these factors may influence the participants' ability to relate to the patients' child wish and it consequently might influence their acceptability of PGD and their responsiveness in referring patients for PGD. Professional variables concerned medical specialty, currently in training (yes/no), years of clinical experience (<10/≥10), average number of patients with BRCA a month (0/1–5/6–10/>10), patients who are eligible for PGD (yes/no) and type of medical centre (general hospital or teaching/university hospital).
Table 1Main questionnaire items.
| Questionnaire items | Answer options |
|---|---|
| Awareness | |
| Did you ever hear about PGD before filling in this questionnaire? | Yes(1)-no(0) |
| Did you know that PGD is an option for couples with BRCA in the Netherlands before filling in this questionnaire? | Yes(1)-no(0) |
| Knowledge of PGD indications (Please select the conditions for which you think PGD is allowed in the Netherlands) | |
| Duchenne and Becker muscular dystrophy | Yes(1)-no(0) |
| Haemophilia A/B | Yes(1)-no(0) |
| Adren leukodystrophy | Yes(1)-no(0) |
| Hereditary motor and sensory neuropathy | Yes(1)-no(0) |
| Chromosomal anomalies (translocations) | Yes(1)-no(0) |
| Fragile X syndrome | Yes(1)-no(0) |
| Hereditary cardiac conditions | Yes(0)-no(1) |
| Cystic fibrosis | Yes(1)-no(0) |
| Spinal muscular atrophy | Yes(1)-no(0) |
| Hereditary breast and ovarian cancer | Yes(1)-no(0) |
| Huntington's disease | Yes(1)-no(0) |
| Gender selection for non-medical reasons | Yes(0)-no(1) |
| Marfan syndrome | Yes(1)-no(0) |
| Myotonic dystrophy | Yes(1)-no(0) |
| Hereditary ataxia | Yes(1)-no(0) |
| Familial adenomatous polyposis | Yes(1)-no(0) |
| All conditions mentioned above | Yes(0)-no(1) |
| None of the conditions mentioned above | Yes(0)-no(1) |
| I do not know | Yes(0)-no(1) |
| Acceptability | |
| I think PGD for BRCA is acceptable | Totally disagree(1)-totally agree(5) |
| I think that the acceptability of PGD for BRCA depends on the personal, family history, or both, of the patient concerning BRCA. | Totally disagree(1)-totally agree(5) |
| I think that the couple should decide whether their genetic predisposition is serious enough to justify PGD. | Totally disagree(1)-totally agree(5) |
| Referral behaviour | |
| Do you ever discuss PGD with patients with BRCA who are eligible for PGD? | Yes(1)-no(0) |
| Do you intend to discuss PGD with patients with BRCA who are eligible for PGD in the future? | No, definitely not (1)-yes, definitely (5) |
| Do you ever refer patients with BRCA for PGD? | Yes(1)-no(0) |
| Do you intend to refer patients with BRCA for PGD in the future? | No, definitely not (1)-yes, definitely (5) |
| Knowledge of PGD procedures (Please select for each statement if it is true, false or if you are not sure) | |
| Questionnaire items: True (T) / False (F) / not sure | Correct answer when statement is false |
| For PGD, an IVF treatment is always necessary (T). | |
| PGD is possible in every academic hospital in the Netherlands (F). | There is only one licensed PGD centre in the Netherlands, but the IVF treatment for PGD can take place at three other geographically dispersed hospitals. |
| Hormone use by the woman is not always necessary for a PGD treatment (F). | As IVF is necessary for PGD, the hormones needed for IVF should always be used by the woman. |
| PGD takes place before the woman is pregnant (T). | |
| When a couple is normally fertile, the chance of a pregnancy after a PGD treatment is nearly 100% (F). | The chance of a pregnancy after a PGD treatment is 20–25%. |
| With a PGD treatment, the affected embryos are preserved (F). | With a PGD treatment, the affected embryos are discarded. |
| In the Netherlands, PGD is only allowed for conditions with a 100% penetrance (F). | In the Netherlands, PGD is also allowed for conditions with an incomplete penetrance such as hereditary cancer predispositions. |
| With PGD, the embryo is also screened for other conditions than the condition of interest (F). | With PGD, the embryo is only diagnosed for the condition or predisposition PGD is aimed at. |
| To date, no additional risks have been identified for PGD compared with regular IVF (T). | |
| The genetic preparation of a PGD treatment takes several months to 1 year (T) | |
| Currently, a maximum of three PGD treatments is reimbursed by the health insurance system in the Netherlands (T). | |
| In the Netherlands, fewer than 100 PGD treatments are carried out on an annual basis (F). | In 2013, 241 couples started a PGD treatment in the Netherlands (293 in 2014 and 329 in 2015). |
| In the Netherlands, couples can also choose the gender of the embryo when undergoing PGD for HBOC (F). | Gender selection for PGD is only allowed in specific cases when the condition of interest is sex-linked. |
| With PGD for HBOC, male embryos with a BRCA mutation are also selected for implantation in the uterus (F). | PGD for BRCA is exclusively aimed at diagnosis of the BRCA mutation irrespective of the gender of the embryo. |
| PGD for BRCA is also allowed for women with a BRCA mutation who have had breast cancer (T). | |
HBOC, hereditary breast and ovarian cancer; PGD, preimplantation genetic diagnosis; PND, prenatal diagnosis.
a At the time of data collection, PGD for hereditary cardiac conditions was not permitted in the Netherlands. At present, this is assessed on a case by case basis by the Dutch National PGD Indications Committee.
b This was correct at the time of data collection. These days, in some centres, aneuploidy screening is added.
Data analysis
Questionnaire data were automatically stored in SPSS version 19.0 (IBM Corp., USA) and consequently analysed. Descriptive statistics were conducted to provide an overview of the four primary outcome measures. Owing to insufficient variation within ‘ethnicity’ this variable was excluded from further analyses. Moreover, because of insufficient variation within the variable ‘medical specialty’, it was impossible to compare the different medical specialties with additional analyses. We did, however, conduct descriptive statistics for the subgroup ‘specialists in genetics’, i.e. clinical geneticists and genetic counsellors: (26%, n = 49), as these are the professionals who are specifically involved in PGD counselling.
To assess associations of demographic or clinical factors with the four outcomes of interest, Pearson correlations, independent sample t-tests and Pearson chi-squared tests were conducted. Mann–Whitney U tests or Spearman correlations were used as non-parametric alternatives when categorical variables were involved. Ultimately, a multiple linear or logistic regression model (enter method) was built for multivariate analyses. A significant outcome was defined as P < 0.05.
Results
Participants' characteristics
In total, 231 professionals participated in this study, of which 188 (81%) completed the questionnaire and were included in the analyses. The remaining 43 participants (19%) dropped out before completing 90% of the questionnaire. From here on, ‘total sample’ refers to the 188 participants that completed the questionnaire. Participants' characteristics are presented in Table 2. Response rates were 14.9% (28/187) for the association of clinical geneticists, 33.8% (22/65) for the association of genetic counsellors, 13.5% (122/902) for the association of gynaecology and obstetrics, and 47.1% (16/34) for the association of oncology.
Table 2Participants' characteristics.
| Demographic variables | % (n) |
|---|---|
| Gender | |
| Male | 22.8 (42) |
| Female | 77.2 (142) |
| Age (years) | |
| Mean (SD) | 45.2 (9.6) |
| Minimum | 30 |
| Maximum | 65 |
| Partner status | |
| Partner | 90 (162) |
| No partner | 10 (18) |
| Children | |
| Yes | 73.4 (135) |
| No | 26.6 (49) |
| Religious | |
| Yes | 18.5 (34) |
| No | 81.5 (150) |
| Ethnicity | |
| Dutch | 92.4 (170) |
| non-Dutch | 7.6 (14) |
| Professional variables | |
| Specialty | |
| Gynaecologist | 63.3 (119) |
| Clinical geneticist | 14.9 (28) |
| Genetic counsellor | 11.7 (22) |
| Medical oncologist | 8.5 (16) |
| Fertility physician | 1.6 (3) |
| In training | |
| Yes | 24.5 (45) |
| No | 75.5 (139) |
| Years of clinical experience (of those not in training: n = 141) | |
| 0–10 | 51.4 (71) |
| ≥11 | 48.6 (67) |
| Average number of BRCA patients per month | |
| <1 | 37.2 (68) |
| ≥1 | 62.8 (115) |
| Contact with eligible PGD patients | |
| Yes | 87.2 (164) |
| No | 10.6 (20) |
| Not sure | 2.1 (4) |
| Type of medical centre | |
| Teaching or university hospital | 47.0 (86) |
| General hospital | 53.0 (97) |
Awareness of PGD for BRCA
Of the total sample, 51% of the professionals were aware of the possibility of PGD for BRCA in the Netherlands, whereas 88% of the specialists in genetics were aware (Supplementary Table S1). Bivariate analysis showed that awareness of PGD for BRCA was positively associated with being female (P = 0.038, chi-squared = 4.30), and with being employed at a teaching or university hospital (P < 0.001, chi-squared = 30.67) (Supplementary Table S2). Multivariate analysis confirmed that participants working at a teaching or university hospital were more likely to be aware of PGD for BRCA (P < 0.001, OR 0.092, CI 95% 0.037 to 0.229) (Supplementary Table S3).
Knowledge of PGD for BRCA
Knowledge of PGD was measured by two scales as described in the Materials and Methods section (Table 1). The 51% of participants who were aware of PGD for BRCA scored a mean of 9.2 (SD 4.6) out of 16.0 on the first scale (allowed PGD indications), with 43% scoring low, 26% scoring moderate and 31% scoring high. The same group scored a mean of 9.8 (SD 3.0) out of 15.0 on the second scale (PGD procedures), with 34% scoring low, 46% scoring moderate and 20% scoring high. The 49% of participants who were not aware of PGD for BRCA scored a mean of 8.6 (SD 2.8) out of 15 on the PGD ‘procedures scale’, with 52% scoring low, 37% scoring moderate and 11% scoring high. The specialists in genetics scored a mean of 12.3 (SD 3.8) on the ‘allowed indications scale’ (with 16% scoring low, 20% scoring moderate and 64% scoring high), and 11.5 (SD 2.1) on the ‘procedures scale’ (with 2% scoring low, 66% scoring moderate and 32% scoring high) (Supplementary Table S1). The specialists in genetics scored significantly higher than the other participants on both knowledge scales (P < 0.001, t = 6.04; P ≤ 0.001, t = 6.94, respectively).
Bivariate analysis showed that both types of knowledge were positively associated with occasionally seeing patients who are eligible for PGD (P < 0.001, t = −3.67; P = 0.003, t = −2.99) and with being employed at a teaching or university hospital (P < 0.001, t = 5.06; P < 0.001, t = 4.85) (Supplementary Table S2). Multivariate analyses confirmed that professionals who occasionally see patients who are eligible for PGD (P = 0.005, β = 0.225; P = 0.018, β = 0.191) and professionals who work at a teaching or university hospital (P < 0.001, β = −0.392; P < 0.001, β = −0.421) are likely to have more knowledge about PGD indications and PGD procedures. Multivariate analyses additionally showed that professionals with a partner had more knowledge about PGD procedures (P = 0.021, β = 0.197) (Supplementary Table S4).
Acceptability of PGD for BRCA
The mean acceptability score of PGD for BRCA was 4.2 (SD 0.8) on a five-item scale for the total sample, which was similar for the specialists in genetics as a subgroup. Eighty-six per cent of the total sample and 92% of the specialists in genetics considered PGD for BRCA acceptable, which did not differ significantly. Nearly one-third (31%) of the total sample believed that PGD acceptability (and therefore approval) should be the patients' autonomous decision (16% of the specialists in genetics) and 29% of the total sample agreed that this should depend on the patients' personal and family history of cancer (40% of the specialists in genetics) (Supplementary Table S1).
Bivariate analyses showed that male participants and those with more knowledge about PGD procedures more often considered PGD for BRCA acceptable (respectively P = 0.005, U = 2277; P = 0.006, rs = 0.020) (Supplementary Table S2). Multivariate analyses showed that men and those who were previously aware of PGD for BRCA were more likely to consider PGD for BRCA acceptable (P = 0.015, β = −0.234; P = 0.019, β = 0.277), whereas religious participants were less likely to consider PGD for BRCA acceptable (P = 0.048, β = −0.173) (Supplementary Table S4).
Discussing and referring for PGD for BRCA
Of the total sample, 13% indicated that they never saw patients who were eligible for PGD. Of this 13%, more than one-half (64%) was not aware that BRCA is a legal indication for PGD. The analyses described in this paragraph were conducted among the subgroup of professionals who indicated that they occasionally saw patients who are eligible for PGD (87% of the total sample). Of this subgroup, 60% indicated that they currently discussed PGD with patients with BRCA (84% of the specialists in genetics), and 93% had the intention to do so in the future (94% of the specialists in genetics). Less than one-half (48%) ever referred a patient with BRCA for PGD (62% of the specialists in genetics), whereas 92% indicated the intention to do so in the future (90% of the specialists in genetics) (Supplementary Table S1).
Bivariate analyses showed that the likeliness of discussing PGD with patients and to refer them for PGD was higher among older participants (P = 0.006, t = −2.79; P = 0.046, chi-squared = −2.01, respectively), participants who were employed at a teaching or university hospital (P < 0.001, chi-squared = 17.81; P = 0.001, X2 = 11.72) and those who had more knowledge about both PGD indications (P < 0.001, t = −4.26; P = 0.003, t = −3.02) and procedures (P < 0.001, t = −4.77; P < 0.001, t = −4.18). Referring for PGD was additionally associated with PGD acceptability (P = 0.037, U = 2956) and discussing PGD (P < 0.001, chi-squared = 77.44). Participants who were still in training were less inclined to discuss PGD (P = 0.005, chi-squared = 8.03) and to refer for PGD (P = 0.040, chi-squared = 4.23) (Supplementary Table S2). Multivariate analyses confirmed that professionals who were employed at a teaching or university hospital (P = 0.002, OR = 0.126, CI 95% 0.035 to 0.455), who had more knowledge about PGD procedures (P = 0.015, OR 1.291, CI 95% 1.051 to 1.585) and those who considered PGD for BRCA acceptable (trend: P = 0.053, OR 1.779, CI 95% 0.992 to 3.194), were more likely to discuss PGD for BRCA with their patients. Additionally, they showed that participants who saw one or more patients with BRCA a month more often discussed PGD (P < 0.001, OR 1.113, CI 95% 0.035 to 0.369) and referred for PGD (P = 0.011, OR 5.195, CI 95% 1.450 to 18.605). A strong trend towards significance additionally suggested that participants who had more knowledge about PGD procedures were also more likely to refer for PGD (P = 0.050, OR 1.209, CI 95% 1.000 to 1.461) (Supplementary Table S3).
Discussion
This study suggests that, overall, one-half of professionals of different specialties (including geneticists) involved in the care of persons with HBOC in the Netherlands are aware of PGD as a reproductive option, whereas this holds for 90% of the specialists in genetics. A minority of the study sample (13%) indicated that they never saw patients who are eligible for PGD or were not sure about this. More than one-half (64%) of this subgroup was not aware that PGD is a reproductive option for BRCA, and was, therefore, not aware of the fact that some of their patients may have been eligible for PGD. The only previous quantitative study that reported awareness of PGD for hereditary cancer syndromes among involved professionals (oncology nurses, USA) found that 22% of professionals were aware of PGD (
Quinn et al, 2014
). In comparison, awareness of PGD for BRCA among involved professionals in the Netherlands may be considered as relatively high. Although professionals with a specialty different than genetics should not necessarily have detailed knowledge about PGD for BRCA, it is important that they are aware of this reproductive option and its criteria for eligibility to refer eligible patients. Awareness was higher among professionals who worked at a teaching or university hospital, where education about relatively novel treatment options such as PGD is considered to be more accessible compared with general hospitals. Moreover, clinical genetics departments are exclusively located in university hospitals in the Netherlands as in many other European countries, which will enhance the possibility to consult and collaborate with clinical geneticists in these settings compared with general hospitals.The mean level of knowledge about both PGD indications and PGD procedures was moderate among the subgroup that was aware of PGD for BRCA. To put this into perspective, we should point out that some of the PGD indications were not relevant to certain specialities, e.g., an oncologist does not need to be aware of the possibility of PGD for non-oncological genetic conditions. The subgroup ‘specialists in genetics' had a high level of knowledge about the approved PGD indications; however, their level of knowledge of PGD procedures was moderate. Prior studies also reported a limited level of knowledge among health professionals (gynaecological oncologists, obstetrics and gynaecologists (
Brandt et al, 2010
) and oncology nurses (Quinn et al, 2014
)) concerning PGD for hereditary cancer syndromes. Participants who at least occasionally saw patients who are eligible for PGD, and those who worked at a teaching or university hospital, had more knowledge about approved PGD indications and procedures, which is in line with expectations, as these subgroups are expected to be the most knowledgeable about PGD. Knowledge about PGD procedures was also higher among respondents with a partner. As 90% of participants had a partner, however, these unequal samples do not allow firm conclusions to be drawn from this result.Acceptability of offering PGD for BRCA was equally high (>85%) among the general sample and the subgroup ‘specialists in genetics’. Previous studies conducted in the USA and Spain reported an acceptability rate of 61–66% regarding PGD for hereditary cancer susceptibility among health professionals (
Fortuny et al, 2009
, Quinn et al, 2014
), whereas Julian-Reynier et al, 2009
reported a 26% acceptability rate of PGD for BRCA among cancer geneticists in France. The relatively high acceptability rate of offering PGD for BRCA found in the present study might be related to the rapid development of PGD during the past few years, which may have increased PGD acceptability overall. Previous studies have shown that, given the moral and ethical dimensions of PGD, acceptability of this reproductive technique for hereditary cancer syndromes is not easy to capture in clear guidelines. Several of these studies found that most health professionals associate PGD acceptability with the nature of the predisposition or the patients' family history of cancer, reproductive history, or both (Julian-Reynier et al, 2009
, Kalfoglou et al, 2005
, Klitzman et al, 2013
), whereas other studies showed that most consider the patients' autonomy of highest value (Ehrich et al, 2007
, Zeiler, 2007
). In the present study, nearly one-third believed that it should be the patients' autonomous decision whether PGD is acceptable (and therefore should be approved for them), and a slightly smaller group believed this should depend on the patients' personal and family history of cancer. In the Netherlands, PGD for BRCA has been legally approved by the national PGD indications committee since 2008. When the committee is uncertain about a request for a new indication, the request is evaluated on a case by case basis in which several aspects are considered, such as the disease burden on the patient and his or her family. It is never the patient's autonomous decision whether PGD is an option.Acceptability of PGD for BRCA was significantly higher among male health professionals, non-religious participants, those who were previously aware of PGD for BRCA and those with more knowledge about PGD procedures. Concerning the higher acceptability among male health professionals, this group was relatively small (23% male compared with 77% female), and additional research is required to confirm this finding and identify any underlying motives. Concerns (mostly moral and ethical) among religious persons about PGD have also been reported; these are based on the belief that PGD selects new life and that it should not be the privilege of human beings to do so (
Quinn et al, 2010
; Rich et al, 2014
, Vadaparampil et al, 2009
). Furthermore, previous awareness and knowledge of PGD have been associated with PGD acceptability (Gietel-Habets et al, 2017
, Meister et al, 2005
), which may indicate that a better understanding of PGD, including its restrictions and limitations, may lead to less moral and ethical reservations and a higher acceptability.A total of 85% of the specialists in genetics discussed PGD with their BRCA-patients, whereas
Julian-Reynier et al, 2009
showed that 59% of the participating French cancer geneticists discussed PGD for hereditary cancer with their patients. Although this may seem like a substantial difference between the Netherlands and France, at the time of the study by Julian-Reynier et al, 2009
, PGD for BRCA was not permitted in France, whereas in the Netherlands it had been permitted for several years at the time of data collection.Less than one-half of participants in the present study who regularly saw patients who are eligible for PGD had ever referred a patient with HBOC for PGD, and 65% of the specialists in genetics had, whereas intention to do so was over 90% in both groups. This referral gap has been previously reported by
Klitzman et al, 2013
and Brandt et al, 2010
who indicated that this may be due to professionals' limited knowledge about PGD, not always enabling them to identify patients for whom PGD is an appropriate option. The present study showed that professionals with more knowledge about PGD were indeed more likely to refer a patient for PGD. Also, professionals who saw patients with BRCA on a monthly basis, and who worked at a teaching or university hospital, more often referred patients with BRCA for PGD. As only university hospitals have clinical genetics departments in the Netherlands, their channels for PGD referral may be more straightforward compared with general hospitals.In both the Netherlands and other countries in which PGD for BRCA is available, it is important to increase awareness and knowledge about this reproductive option among the involved professionals. In a way, these healthcare providers are the gatekeepers of reproductive techniques such as PGD, and patients depend on them to know their options in order to make an informed choice.
Limitations
When interpreting the results of this study, several limitations need to be considered. To achieve conciseness of the survey and to prevent dropout, some concepts were assessed by a limited number of items, which may have reduced content validity. In addition, the response rates of some groups of medical specialists were relatively low, and medical oncologists are underrepresented in this study. This is, however, the largest sample to date exploring this topic among specialists in genetics who are primarily involved in PGD. It is known that overall response rates have been decreasing over the past few years, especially among medical specialists (
Cull et al, 2005
, Gaela, Tracy, 2007
). Moreover, low response rates do not necessarily result in selection bias (Cull et al, 2005
), which is even less probable among medical specialists who are considered relatively homogenous as a group (in terms of education, knowledge, attitudes and behaviour) compared with the general population (Asch et al, 2000
, Kellerman, Harold, 2001
). Ultimately, 43 participants dropped out at variable stages in the questionnaire, possibly owing to the length of the questionnaire. This may have skewed outcomes as drop out might have been higher among professionals who are least involved in, or in favour of, PGD.Implications for practice
In the Netherlands, as in many other countries, no official guidelines are available for professionals on discussing and referring for PGD. The ongoing controversy about its approval for hereditary cancer syndromes, and the variable knowledge and attitudes of professionals about PGD, emphasize the need for clear standard of care guidelines within onco-genetics. Couples with HBOC should be made aware of their reproductive options, including PGD, so they can make an informed decision and negative psychological effect (such as doubt or decisional regret) can be minimized. To achieve this, we should start by optimizing awareness and knowledge among healthcare providers who are trusted to be one of the main sources of information by their patients. The motives of professionals in deciding whether or not to refer for PGD should be further investigated, and awareness about PGD should be enhanced by means of additional education, especially in non-university hospitals. Extensive education about this topic for these professionals with limited time and pressure to stay up to date on new developments in their field may not be required as counselling about PGD should primarily be the responsibility of the clinical geneticist; however, the involved professionals should be aware of patients' options and have sufficient knowledge to identify patients who are eligible for PGD and refer them if desired. Furthermore, referral for PGD should become more embedded in our healthcare system; for example, by inserting a standard sentence about the possibility of PGD in the patient or family letter concerning the DNA-result in case of BRCA1/2 mutation.
Acknowledgements
We would like to thank the Dutch breast cancer foundation Stichting Pink Ribbon for funding this study, grant number 2010.PS11.C74. Moreover, we would like to thank the VKGN (Vereniging Klinische Genetica Nederland), the NVGC (Nederlandse Vereniging voor Genetisch Consulenten), the NVOG (Nederlandse Vereniging voor Obstertrie en Gynaecologie), and the NVvO (Nederlandse Vereniging voor Oncologie) for their contribution to this study.
Appendix. Supplementary material
The following is the supplementary data to this article:
- Table S1
Awareness, knowledge and acceptability of PGD for BRCA, and referral behaviour among specialists and non-specialists in genetics.
- Table S2
Correlates of demographic and medical characteristics with the main outcome variables (bivariate analyses).
- Table S3
Associations between demographic, medical characteristics and awareness and referral behaviour PGD (logistic regressions).
- Table S4
Associations between demographic and medical characteristics, and knowledge and acceptability of PGD (linear regressions).
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Biography
Dr Joyce Gietel-Habets studied Health Education and Promotion at the University of Maastricht. She works at the Department of Clinical Genetics at Maastricht University Medical Centre researching psycho-social aspects of PGD, and as a case manager for PGD. These two positions enable her to link research implications to patient care.
Key message
Professionals who are aware of PGD are more likely to consider PGD for BRCA; professionals who are knowledgeable about PGD are more inclined to discuss this option with patients and make a referral. Awareness and knowledge of PGD should be optimized to inform reproductive decision making among patients with BRCA.
Article info
Publication history
Published online: December 01, 2017
Accepted:
November 15,
2017
Received in revised form:
November 4,
2017
Received:
June 7,
2017
Declaration: The authors report no financial or commercial conflicts of interest.Identification
Copyright
© 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
