Purpose Due to limited health literacy and resulting ineffective communication between healthcare professionals and patients, not all eligible patients are offered breast cancer genetic counseling and testing. We aimed to develop a plain-language guide to increase effective communication about genetic counseling and testing with breast cancer patients with limited health literacy. Methods Together with oncological healthcare professionals, we drafted a list of jargon words frequently used during (breast) cancer genetic counseling. In a focus group interview with breast cancer counselees with limited health literacy, who had received genetic counseling before, we reformulated these words in plain language. Low-literate individuals, who are not familiar with breast cancer care or genetic counseling, reflected on the draft of the guide. Completeness, acceptability, and perceived usability were tested in an online questionnaire among healthcare professionals. Results The result is a plain-language guide for genetic counseling and testing with 33 frequently used jargon words and a reformulation of these words in plain language. Acceptability and perceived usefulness of the guide among healthcare professionals ( n = 58) were high. Conclusion The plain-language guide provides opportunities to facilitate communication about genetic counseling and testing with patients with limited health literacy and could enhance opportunities for patients to make informed decisions to participate in genetic testing. As the intention from healthcare professionals to use the plain-language guide is high, implementation of the guide in a real-life setting seems promising.

Lower participation rates in cancer genetic counseling are observed among different ethnic minorities. The goal of our study is to gain insight into determinants of Turkish and Moroccan patients’ participation in breast cancer genetic counseling and DNA testing, from the point of view of healthcare professionals and patients. Questionnaire-based telephone interviews about awareness, perceptions, and reasons for (non-) participation in cancer genetic counseling were conducted with 78 Dutch breast cancer patients from Turkish and Moroccan descent. The interviews were held in Arabic, Berber, Turkish, or Dutch by bilingual research assistants. Additionally, 14 breast cancer patients participated in one of two focus group meetings, and two focus groups were held with 11 healthcare professionals. SPSS and QSR Nvivo were used to examine the quantitative and qualitative data, respectively. Half of the total group of patients ( N = 78) and 79% of patients eligible for genetic counseling and testing ( N = 33) were aware of the possibility of genetic counseling. The most important determinants for nonparticipation in genetic counseling were experienced difficulties in patient-doctor communication, cultural factors (e.g., social norms), limited health literacy, limited knowledge of the family cancer history, and anxiety about cancer. Religious beliefs and knowing personal and family members’ breast cancer risks were motives to obtain genetic counseling. Despite the fact that our study showed that Moroccan and Turkish women reported several personal motives to obtain genetic counseling and testing (GCT), patients and healthcare professionals experience significant language and health literacy difficulties, which make it harder to fully access health care such as genetic counseling and testing.

Participation rates in cancer genetic counseling differ among populations, as patients with a lower educational background and migrant patients seem to have poorer access to it. We conducted a study to determine the present-day educational level and migrant status of counselees referred to cancer genetic counseling. We assessed personal characteristics and demographics of 731 newly referred counselees. Descriptive statistics were used to describe these characteristics. The results show that about 40% of the counselees had a high educational level and 89% were Dutch natives. Compared to the Dutch population, we found a significant difference in educational level (p = < 0.01) and migrant status (p = < 0.001). This suggests disparities in cancer genetic counseling and as a result of that, suboptimal care for vulnerable groups. Limited health literacy is likely to pose a particular challenge to cancer genetic counseling for counselees with a lower education or a migrant background. Our study points to considerable scope for improvement in referring vulnerable groups of patients for cancer genetic counseling.

Inconclusive genetic test results including screening recommendations for the breast cancer patients and their first-degree relatives are the most common outcomes of BRCA 1/2 testing. Patients themselves should communicate these results to their relatives. Our aim was to explore communication of breast cancer genetic counseling results with daughters and sisters over a long period of time. Breast cancer patients, who had received an inconclusive DNA test result 7–14 years earlier, completed a self-report questionnaire. Additionally, in-depth interviews were conducted and analysed thematically. Of the 93 respondents, 85 (91 %) considered themselves responsible for communicating genetic test results to relatives. In-depth interviews (n = 14) showed, that counselees wanted ‘to hand over’ their responsibilities to communicate the test results and screening recommendations to their sisters. Although most patients had informed their daughters and sisters about the genetic test results, usually little is spoken about genetic test results and screening recommendations once the duty of informing is completed. We recommend that, similar to the procedure for BRCA1/2-mutation carriers, a separate letter for first-degree relatives of patients with an inconclusive test result should be provided. In this way information about risks and screening recommendations can be verified by family members years after genetic testing has been completed.

Genetic counseling and DNA testing ( GCT ) for breast cancer is increasingly being actively offered to newly diagnosed patients. Little is known about the consequences of such an approach. Therefore, the long‐term psychosocial and medical impact of referring breast cancer patients for GCT during an early phase of treatment was studied. A group of 112 breast cancer patients who had been actively offered GCT during adjuvant radiotherapy 7–14 years earlier, returned a self‐report questionnaire. We compared their experiences with a group of 127 breast cancer patients who had not met the criteria for GCT . In total, 239 women participated in this long‐term follow‐up study (72% response rate). Nearly 75% of them had received regular mammography surveillance in the past 3 years. Preventive surgery was reported more often in the counseling group (specifically in the BRCA1 /2 mutation carriers). Like the comparative group, only a minority of patients who had received GCT were experiencing high levels of depression (5%) or psychological distress (14%). Breast cancer patients can be actively approached and referred for GCT at the beginning of their radiotherapy without a threat to psychological functioning in the long term.

Objective: The referral process for genetic counselling in breast cancer patients may be compromised by patient-related factors, like patient’s age, referral initiative or cancer history. This study aimed to characterize this referral process in daily clinical practice. Methods: During genetic counselling a checklist was filled in for each consecutive counselee affected with breast cancer assessing educational level, the initiator for referral and the ethnic background as reported by the counselee. Chi-square tests were used to assess associations between patient-related factors and initiator of referral and timing of genetic counselling. Results: Included were 96 consecutive breast cancer patients referred to cancer genetic counselling: 52% of them were referred on their own initiative versus 48% on their doctor’s initiative. There was no significant relationship between initiator of referral and time since diagnosis, age at time of diagnosis, number of first-degree female relatives and number of first degree relatives affected by any cancer. Discussion: Patients’ interest in genetic testing is not clearly related with time since diagnosis. Family history seems to play a role in the timing for referral. Conclusion: At one out of two breast cancer patients plays a major role in the referral for genetic counselling. However, we did not establish a relationship between initiative for referral and time since diagnosis. (aut. ref.)

Both physician and patient play a role in the referral process for cancer genetic counseling. Access to such counseling is not optimal because some eligible patients are not being reached by current referral practice. We aimed to identify factors associated with the initiator of referral. During a 7-month period, we recorded demographic characteristics like gender, personal and family history of cancer, ethnicity and eligibility for genetic testing for 406 consecutive counselees using a specially designed questionnaire. Counselees were seen in a university hospital or a community hospital (n = 7) in the Netherlands. We also recorded educational level of each counselee, clinical setting and who initiated referral. Descriptive statistics were used to describe the counselees’ general characteristics. We analysed the association between counselee characteristics and the initiator of referral by logistic regression. The majority of counselees seemed to have initiated referral themselves but were indeed eligible for genetic testing. In comparison to the general population in the Netherlands, the counselees had a higher level of education, and there were fewer immigrants, although a higher level of education was not found to be a facilitating factor for referral. The clinical setting where a counselee was seen was associated with initiator of referral, although this relationship was not straightforward. There is a complex interaction between clinical setting and initiator of referral, which warrants further research to elucidate the factors involved in this relationship. Patients seen in cancer genetic counseling do not reflect the general population in terms of educational level or ethnicity.

e14616 Background: Carriers of a CDH1 gene mutation have a risk of up to 80% to develop gastric cancer (GC). Prophylactic total gastrectomy is offered to mutation carriers to prevent invasive GC development. In this usually young and asymptomatic population, however, the psychosocial, physical and nutritional consequences are largely unknown. Therefore, the aim of this study was to investigate the impact of preventive gastrectomy in CDH1 mutation carriers. Methods: Questionnaires were sent to individuals with a CDH1 gene mutation, who had undergone a prophylactic gastrectomy. Disease-free sporadic GC patients, who had undergone a total gastrectomy 2-5 years earlier also received these questionnaires and served as a comparison group. The questionnaire assessed psychosocial (quality of life [QLQ C30, STO22], anxiety and depression [HADS], social impairment), physical (fatigue [CIS]) and nutritional variables. Results: Of the 21 CDH1 carriers who had a prophylactic gastrectomy, 20 (95%) participated (45% males). Of 23 addressed GC patients, 20 (87%) participated (70% males). Mean age was 41 years (range 20-68 years) and 59 years (range 37-74), respectively. Mean time since gastrectomy was 34 months (SD= 18 months, range 5-63 months) and 47 months (SD= 22 months; range 15-80 months), respectively. The levels of quality of life, anxiety, depression, and fatigue as reported by the two groups (preventive vs. curative resection) did not differ significantly. All together, 48% reported complaints about fatigue (28% had severe fatigue), and 18-48% of the patients reported (severe) impairment in daily activities (work, hobbies, personal relationships). Mean ±SD weight loss of 15% ± 6% was found. Food and drink products that patients were unable to consume were: dairy products (73%), fried products (25%), and soft drinks (13%). Conclusions: Following total gastrectomy, patients experience fatigue, impairment of everyday life, and weight loss. Patients with a preventive gastrectomy (carriers) did not differ from cancer patients treated by a curative gastrectomy. However, complaints varied widely among participants.

CDH1 mutation carriers have a strongly increased risk of developing gastric cancer (GC) and lobular breast cancer (LBC). Clinical data of GC cases and surgical and histological data of prophylactic gastrectomies and mastectomies of all 10 Dutch CDH1 mutation families were collected. In vitro functional assays were performed to analyze the nature of the newly found missense mutation c.1748T>G (p.Leu583Arg). Ten different CDH1 mutations were found. Functional assays gave strong arguments for the pathogenic nature of the p.Leu583Arg mutation. The pedigrees comprised 36 GC cases (mean age 40 years, range 20-72 years) and one LBC case. Twenty-nine/37 carriers alive, aged 18-61 years, underwent prophylactic gastrectomy. Invasive GC-foci and premalignant abnormalities were detected in 2 and 25 patients, respectively. In four patients GC/signetring cell (SRC) foci were diagnosed at preoperative gastroscopy. Long-standing presence of SRCs without progression to invasive carcinoma was shown in two others. Multifocal LBC/LCIS was found in the two prophylactic mastectomy specimens. Clefts of lip and/or palate (CL/P) were reported in seven individuals from three families. The age at onset and aggressiveness of GC is highly variable, which has to be included in counseling on planning prophylactic gastrectomies. The incidence of LBC is expected to increase and prophylactic mastectomy needs to be considered. The relationship between CL/P and CDH1 needs further study to inform future parents from hereditary diffuse gastric cancer (HDGC) families adequately.

BACKGROUND:An unclassified variant (UV) in exon 1 of the MLH1 gene, c.112A > C, p.Asn38His, was found in six families who meet diagnostic criteria for Lynch syndrome. The pathogenicity of this variant was unknown. We aim to elucidate the pathogenicity of this MLH1 variant in order to counsel these families adequately and to enable predictive testing in healthy at-risk relatives.METHODS:We studied clinical data, microsatellite instability and immunohistochemical staining of MMR proteins, and performed genealogy, haplotype analysis and DNA testing of control samples.RESULTS:The UV showed co-segregation with the disease in all families. All investigated tumors showed a microsatellite instable pattern. Immunohistochemical data were variable among tested tumors. Three families had a common ancestor and all families originated from the same geographical area in The Netherlands. Haplotype analysis showed a common haplotype in all six families.CONCLUSIONS:We conclude that the MLH1 variant is a pathogenic mutation and genealogy and haplotype analysis results strongly suggest that it is a Dutch founder mutation. Our findings imply that predictive testing can be offered to healthy family members. The immunohistochemical data of MMR protein expression show that interpreting these results in case of a missense mutation should be done with caution.

This study explores knowledge about hereditary breast cancer, attitudes about BRCA testing and referral pattern to a family cancer clinic among medical specialists. A total of 92 questionnaires were completed by surgeons (38), medical oncologists (29), radiation oncologists (13) and radiologists (12). The response rate was 51%. A substantial (11-56%) proportion of medical specialists do not refer patients who meet current criteria for BRCA testing. Although questions on inheritance were less well answered, overall knowledge was good. They had a positive attitude, but were concerned about the distress DNA testing might cause to family members. The majority (75%) stated that the best time for referral is after adjuvant therapy or during follow-up, but another important determinant was the patient's wish or need (12%). Further studies are needed to gain insight into the actual referral process, while ongoing training of medical specialists about genetic aspects of breast cancer is also necessary.

Prolonged over-exposure of rats to corticosterone attenuates 5-HT1A-receptor-mediated responses in hippocampal CA1 cells through an unknown mechanism, not involving downregulation of 5-HT1A receptor expression. We here tested if corticosterone changes 5-HT1A receptor function indirectly, by altering hippocampal mRNA expression of NCAM, SGK1, or RGS4, which all modulate 5-HT1A receptor function. We found that the expression of none of these candidates was affected by corticosterone treatment.