Aad Tibben

Psychological distress in applicants for predictive DNA testing for autosomal dominant, heritable, late onset disorders. The Rotterdam/Leiden Genetics Workgroup.

In a comparative study on the effects of predictive DNA testing for late onset disorders, pre-test psychological distress was assessed in people at risk for Huntingtons disease (HD, n = 41), cerebral haemorrhage (HCHWA-D, n = 9), breast and ovarian cancer (HBOC, n = 24), and polyposis coli (FAP, n = 45). Partners, if available, also participated in the study. Distress was measured with the subscales Intrusion and Avoidance of the Impact of Event Scale. People at risk for the neurodegenerative disorders reported more avoidance than those at risk for the cancer syndromes. People at risk for FAP and partners of those at risk for HBOC reported less intrusion than the others at risk and the other partners. Subjects who were more distressed reported more experiences with the disease in close relatives, the disease having a great impact on their lives, having considerations against predictive testing, expecting that being identified as a gene carrier would have adverse effects, and expecting relief after being identified as a non-carrier. Test candidates who expected an increase of personal problems showed higher avoidance, whereas those who could better anticipate future life as a carrier had higher intrusion levels. Generally, subjects with high distress levels are of more concern to the healthcare professional than those with low distress levels. However, high distress may reflect worrying as a mental preparation for the test result, whereas low distress may indicate denial-avoidance behaviour and poor anticipation of the test outcome. In pre-test counselling sessions, this should be acknowledged and addressed.

Impact of screening for breast cancer in high-risk women on health-related quality of life.

The effectiveness of intensive surveillance in women at high risk for breast cancer due to a familial or genetic predisposition is uncertain and is currently being evaluated in a Dutch magnetic resonance imaging (MRI) screening (MRISC) study, in which annual imaging consists of mammography and MRI. Unfavourable side effects on health-related quality of life may arise from this screening process. We examined the short-term effects of screening for breast cancer in high-risk women on generic health-related quality of life and distress. A total of 519 participants in the MRISC study were asked to complete generic health-status questionnaires (SF-36, EQ-5D) as well as additional questionnaires for distress and items relating to breast cancer screening, at three different time points around screening. The study population showed significantly better generic health-related quality of life scores compared to age-/sex-adjusted reference scores from the general population. Neither generic health-related quality of life scores nor distress scores among the study sample (n=334) showed significant changes over time. The impact of the screening process on generic health status did not differ between risk categories. Relatively more women reported mammography as quite to very painful (30.1%) compared to MRI. Anxiety was experienced by 37% of the women undergoing MRI. We conclude that screening for breast cancer in high-risk women does not have an unfavourable impact on short-term generic health-related quality of life and general distress. In this study, high-risk women who opted for regular breast cancer screening had a better health status than women from the general population.

Body image issues after bilateral prophylactic mastectomy with breast reconstruction in healthy women at risk for hereditary breast cancer

The outcome of bilateral prophylactic mastectomy with breast reconstruction (BPM-IBR) in healthy BRCA1/2 mutation carriers can be potentially burdensome for body image and the intimate relationship. Therefore, in the current analysis the impact on body image, sexual and partner relationship satisfaction was prospectively investigated in women opting for BPM-IBR as well as cancer distress and general quality of life. Healthy women undergoing BPM-IBR completed questionnaires preoperatively (T0, nxa0=xa048), at 6xa0months (T1, nxa0=xa044) and after finishing breast reconstruction (median 21xa0months, range 12–35) (T2, nxa0=xa036). With multi-level regression analyses the course of outcome variables was investigated and a statistically significant change in body image and/or sexual and partner relationship satisfaction was predicted by baseline covariates. Body image significantly decreased at T1. At T2 sexual relationship satisfaction and body image tended to be lower compared to baseline. The overall partner relationship satisfaction did not significantly change. At T2, 37xa0% of the women reported that their breasts felt unpleasantly, 29xa0% was not satisfied with their breast appearance and 21xa0% felt embarrassed for their naked body. Most body image issues remained unchanged in 30xa0% of the women. A negative body image was predicted by high preoperative cancer distress. BPM-IBR was associated with adverse impact on body image in a substantial subgroup, but satisfaction with the overall sexual and partner relationship did not significantly change in time. The psychosocial impact of BPM-IBR in unaffected women should not be underestimated. Psychological support should ideally be integrated both before and after BPM-IBR.

High satisfaction rates in women after DIEP flap breast reconstruction.

BACKGROUNDnBreast reconstruction (BR) is aimed at improving quality of life (QoL) after mastectomy. Patient satisfaction is an important indicator to evaluate the success of BR. This study explored patient satisfaction and its determinants in women undergoing deep inferior epigastric artery perforator (DIEP) flap BR as well as the impact of the procedure on body image, sexuality and QoL.nnnMETHODSnPatient satisfaction and QoL were studied in 72 women who underwent DIEP flap BR using a study-specific questionnaire as well as the Short Form-36 (SF-36).nnnRESULTSnPatient satisfaction was very high. Approximately 90% of the patients reported that they had been sufficiently informed about the procedure and its consequences, that their preoperative expectations had been met, that the reconstructed breast felt like their own and that they would choose the same procedure again and would recommend this procedure to a friend. Patient satisfaction was positively and significantly related to the reconstructed breast(s) feeling like their own. Women with secondary reconstructions were more positive about changes in sexuality and femininity than women with primary BRs. There were no clinically relevant differences in QoL between our study population and a random sample of Dutch females.nnnCONCLUSIONSnWomen with DIEP flap BRs reported high satisfaction rates. However, to compare these satisfaction rates with other forms of BR, prospective studies in comparable groups are necessary.

Predictive Genetic Testing for Cardiovascular Diseases: Impact on Carrier Children

We studied the experiences of children identified by family screening who were found to be a mutation carrier for a genetic cardiovascular disease (Long QT Syndrome (LQTS), Hypertrophic Cardiomyopathy (HCM), Familial Hypercholesterolemia (FH)). We addressed the (a) manner in which they perceive their carrier status, (b) impact on their daily lives, and (c) strategy used to cope with these consequences. Children (aged 8–18) who tested positive for LQTS (nu2009=u200911), HCM (nu2009=u20096) or FH (nu2009=u200916), and their parents participated in semi‐structured audiotaped interviews. Interview topics included illness perception, use of medication, lifestyle modifications, worries, and coping. Each interview was coded by two researchers. The qualitative analysis was guided by Leventhals model of self‐regulation. The children were overall quite articulate about the disease they were tested for, including its mode of inheritance. They expressed positive future health perceptions, but feelings of controllability varied. Adherence and side‐effects were significant themes with regard to medication‐use. Refraining from activities and maintaining a non‐fat diet were themes concerning lifestyle modifications. Some children spontaneously reported worries about the possibility of dying and frustration about being different from peers. Children coped with these worries by expressing faith in the effectiveness of medication, trying to be similar to peers or, in contrast, emphasizing their “being different.” Children generally appeared effective in the way they coped with their carrier status and its implications. Nevertheless, dealing with the daily implications of their condition remains difficult in some situations, warranting continued availability of psychosocial support.

Genetic testing in hereditary non-polyposis colorectal cancer families with a MSH2 , MLH1 , or MSH6 mutation

About 5% of colorectal cancers are associated with the autosomal dominantly inherited cancer susceptibility syndrome hereditary non-polyposis colorectal cancer (HNPCC).1,2 HNPCC is characterised by a high risk of developing colorectal cancer and endometrial cancer at a young age (cumulative lifetime risk 80-90% and 30-40%, respectively), and by an increased risk of developing various other tumour types, such as ovarian, uroepithelial, small intestine, biliary tract, stomach, brain, and skin cancers.2–5 Germline mutations in one of three mismatch repair genes ( MSH2 , MLH1 , and MSH6 ) were found to be responsible for a majority of HNPCC families.6–9nnKnowledge of the causative mutation in a particular HNPCC family enables the identification of at risk family members by genetic testing. Clearly, the absence or presence of a mutation is of considerable medical and psychological significance. Subjects not carrying the mutation are relieved from a continuous anxiety and can be dismissed from medical surveillance, saving them trouble and reducing health care costs.10 Importantly, subjects with the mutation can benefit from a medical surveillance programme. For HNPCC, colonoscopy has been shown to be a potent tool for the detection and treatment of premalignant adenomas or early colorectal carcinomas in at risk subjects, reducing the risk of developing colorectal cancer and decreasing the overall mortality by about 65%.11,12 The possibility of early detection of colorectal cancer by stool analysis using the genetic markers TP53, BAT26, and K-RAS raises expectations for the development of less invasive surveillance procedures.13 Furthermore, intervention trials with non-steroidal anti-inflammatory drugs (NSAID) in subjects at risk for developing colorectal cancer are in progress.14,15nnSo far, studies on the use of genetic testing in HNPCC families have used families or subjects who had been registered for research purposes.10,16,17 It is …

Feeling at risk: How women interpret their familial breast cancer risk

Womens inaccuracy in recalling their breast cancer risk, even immediately after genetic counseling, has received much attention. However, scarce data are available about how women describe their risk in their own words and about what the risk information actually means to them. The present study aims to address interpretations questions and to assess whether these are congruent with the objective risk. Face‐to‐face interviews were conducted with 123 women immediately after their (initial) counseling session. N‐Vivo software was used to describe the data. The level of accuracy of recall depended strongly on the leniency of the criterion applied. For example, the level of verbal accuracy ranged from 25.8% (an exact match with the verbal label) to 98.4% (a more global awareness of having a high versus a low risk). In assessing the significance of personal risk information, we identified a wide variety of risk beliefs, and stress and coping responses. In general, women associated their risk with the medical options, for example, breast screening, that were available for them given their risk status. The results indicate that the accuracy of recall might be a limited outcome measure for the effectiveness of genetic counseling. First, this is because the level of accuracy of recall depends on how rigorously accuracy is defined. Secondly, because the probability of occurrence is just one of the elements comprising perceived risk, accuracy might rather apply to the distress, and to risk management behaviors that are elicited by the risk information. These beliefs that women hold about their risk status, and concomitant levels of stress should play a prominent role in genetic counseling.

Psychological Distress and Breast Self-Examination Frequency in Women at Increased Risk for Hereditary or Familial Breast Cancer

Background: The Magnetic Resonance Imaging Screening study evaluates the efficacy and psychological impact of a surveillance program for women at increased risk for hereditary or familial breast cancer in the Netherlands. Surveillance consists of biannual physical examination, annual mammography, annual MRI and monthly breast self-examination (BSE). Objective: To examine the association between psychological distress and reported BSE frequency. Methods: Two months prior to surveillance demographics, BSE frequency, general distress (Hospital Anxiety and Depression Scale and the somatic scale of the Symptom Checklist-90) and breast cancer-specific distress (Impact of Event Scale) were assessed in 316 women (mean age 40.5 years, range 21–63 years). Results: The majority (57%) reported performing monthly BSE. Ten percent reported never performing BSE, 20% less frequently than once a month and 13% at least once a week. Women below the age of 40 who examined their breasts more frequently than recommended (i.e. at least once a week) were shown to be significantly more distressed than the other women in the sample (p = 0.03). These women represented 15% of all the women below the age of 40 years in our study sample. Conclusion: Higher breast cancer-specific distress scores were observed among younger women who examined their breasts at least once a week. It is important for physicians to be aware of this hypervigilant behaviour, especially since it is correlated with breast cancer-specific distress.

Women's motives to opt for either implant or DIEP-flap breast reconstruction.

OBJECTIVEnUnderstanding womens motives concerning breast reconstructive surgery will contribute to a better counselling and care for the increasing number of women choosing post-mastectomy breast reconstruction (BR).nnnMETHODSnWe interviewed 31 women who opted for implant or deep inferior epigastric perforator (DIEP)-flap BR after therapeutic or prophylactic mastectomy. Motives for BR in general and for the selected type of BR were investigated following a phenomenological qualitative research approach.nnnRESULTSnWomen opting for implant BR were concerned with surgery-related issues, such as recovery time, number of scars and impact of surgery. They wanted to return to their daily life and restore their body image as soon as possible. Patients choosing DIEP-flap BR were more focussed on regaining a natural breast and wanted to benefit from the advantages of autologous tissue. Women scheduled for prophylactic mastectomy saw BR as an integral part of their treatment. Patients opting for BR after therapeutic mastectomy wanted to regain a complete body image with BR.nnnCONCLUSIONSnPatients motives for implant BR were primarily related to surgical issues, whereas women who chose DIEP-flap BR especially focussed on regaining a breast that resembles their own lost breast as well as possible. Clinical variables (such as therapeutic or prophylactic mastectomy, breast irradiation, and waiting lists) need to be taken into account when considering a certain type of BR, as these can be of great importance in the decision-making process.

Duchenne/Becker muscular dystrophy in the family: have potential carriers been tested at a molecular level?

Helderman‐van den Enden ATJM, van den Bergen JC, Breuning MH, Verschuuren JJGM, Tibben A, Bakker E, Ginjaar HB. Duchenne/Becker muscular dystrophy in the family: have potential carriers been tested at a molecular level?