¿Cuál es el impacto emocional de los resultados de estudios genéticos en pacientes oncológicos con sospecha de síndrome hereditario para cáncer? / What is the emotional impact of the genetic test results on oncologic patients with suspected hereditary cancer syndrome?

Objetivos: valorar el impacto emocional de recibir los resultados del estudio genético (EG) en pacientes con antecedente oncológico personal y sospecha de síndrome hereditario, aplicando el Cuestionario Multidimensional del Impacto de la evaluación de riesgo de cáncer (MICRA). Método: 219 pacientes con diagnóstico oncológico que concurrieron a la consulta de Asesoramiento Genético Oncológico en el Instituto Alexander Fleming entre 2014 y 2019, fueron evaluados aplicando el MICRA. Resultados: Edad promedio 49,84 (42,21; 62,02), 82,2% con diagnóstico de cáncer de mama. En un 16% se halló una variante patogénica (VP). La media de los puntajes obtenidos por cada subescala fue: 5,26 (DS=4,48, rango 0-22) para Malestar Emocional (ME); 12,31 (DS 7,42 rango 0-37) para Incertidumbre (I); 16,36 (DS 4.30 rango 2-20) para Experiencias Positivas (EP) y de 34,37 (DS 10,24 rango 8-62) para la puntuación global, lo que muestra un bajo nivel de ME e I y la presencia de EP entre los pacientes. Se hallaron diferencias significativas según tipo de resultado: los portadores de VP, mostraron una modesta elevación del nivel de ME y menor puntuación en EP, respecto de aquellos que tuvieron resultados no informativos o inciertos. Sin diferencias significativas según edad, pacientes con o sin hijos, o tiempo entre la realización del estudio y la aplicación del cuestionario. Conclusiones: Recibir resultados de estudio genético no produciría un impacto psicológico adverso. Las puntuaciones altas de esta escala podrían ser usadas para identificar a pacientes con malestar emocional y ofrecerles un seguimiento psicooncológico específico (AU)

Objective: The aim of our study is to assess the emotional impact of genetic test results disclosure to patients with a personal cancer history and suspected hereditary syndrome, applying the Multidimensional Impact of Cancer Risk Assessment (MICRA) Questionnaire. Methods: two hundred nineteen patients affected with cancer, referred to the Cancer Genetic Counseling department at the Alexander Fleming Institute, between 2014 and 2019, were evaluated using the MICRA questionnaire. Results: Average age 49.84 (42,21; 62,02), 82.2% presented breast cancer. In 16% a pathogenic variant (PV) was found. The mean of the scores obtained for each subscale in the questionnaire was 5.26 (0-22, SD 4.48) for Distress (D); 12.31 (0-37, DS 7.42) for Uncertainty (U); 16.36 (2-20 SD 4.30) for Positive Experiences (PE) and 34.37 (8-62 SD 10.24) for the global score, which shows a low level of D and U and the presence of PE among the patients. Significant differences were found according to the type of result: We found modestly increased distress in PV carriers compared to patients who received uninformative or negative test results. No significant differences according to age, patients with or without children, or time between the completion of the genetic test and the application of the questionnaire. Conclusion: Genetic test disclosure does not seem to produce an adverse psychological impact. High scores on this scale could be used to identify patients with emotional distress and offer them specific psycho-oncological follow-up (AU)

Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial.

BACKGROUND: In the KEYNOTE-177 study, pembrolizumab monotherapy provided statistically significant and clinically meaningful improvements in progression-free survival versus chemotherapy as first-line treatment in patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer. To further support the efficacy and safety findings of the KEYNOTE-177 study, results of the health-related quality of life (HRQOL) analyses are reported here. METHODS: KEYNOTE-177 is an open-label, randomised, phase 3 trial being done at 192 cancer centres in 23 countries, in patients aged 18 years and older with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and who had not received previous systemic therapy for metastatic disease. Eligible patients were randomly assigned (1:1) centrally by use of interactive voice response or integrated web response technology to receive pembrolizumab 200 mg intravenously every 3 weeks or investigator's choice chemotherapy (mFOLFOX6 [leucovorin, fluorouracil, and oxaliplatin] or FOLFIRI [leucovorin, fluorouracil, and irinotecan] intravenously every 2 weeks with or without intravenous bevacizumab or cetuximab). Patients and investigators were not masked to treatment assignment. The primary endpoints were progression-free survival (previously reported) and overall survival (data to be reported at the time of the final analysis). HRQOL outcomes were evaluated as prespecified exploratory endpoints. The analysis population comprised all randomly assigned patients who received at least one dose of study treatment and completed at least one HRQOL assessment. HRQOL outcomes were mean change from baseline to prespecified week 18 in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EORTC Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29) scale and item scores, and in the EuroQoL 5 Dimensions 3 Levels (EQ-5D-3L) visual analogue scale and health utility scores; the proportion of patients with improved, stable, or deteriorated scores from baseline to prespecified week 18 in EORTC QLQ-C30 scales and items; and time to deterioration in EORTC QLQ-C30 global health status/quality of life (GHS/QOL), physical functioning, social functioning, and fatigue scores and EORTC QLQ-CR29 urinary incontinence scores. The threshold for a small and clinically meaningful mean difference in EORTC QLQ-C30 score was 5-8 points. This study is registered with ClinicalTrials.gov, NCT02563002 and is ongoing; recruitment is closed. FINDINGS: Between Feb 11, 2016, and Feb 19, 2018, 307 patients were enrolled and randomly assigned to receive pembrolizumab (n=153) or chemotherapy (n=154). The HRQOL analysis population comprised 294 patients (152 receiving pembrolizumab and 142 receiving chemotherapy). As of Feb 19, 2020, median time from randomisation to data cutoff was 32·4 months (IQR 27·7-37·8). Least squares mean (LSM) change from baseline to prespecified week 18 showed a clinically meaningful improvement in EORTC QLQ-C30 GHS/QOL scores with pembrolizumab versus chemotherapy (between-group LSM difference 8·96 [95% CI 4·24-13·69]; two-sided nominal p=0·0002). Median time to deterioration was longer with pembrolizumab versus chemotherapy for GHS/QOL (hazard ratio 0·61 [95% CI 0·38-0·98]; one-sided nominal p=0·019), physical functioning (0·50 [95% CI 0·32-0·81]; one-sided nominal p=0·0016), social functioning (0·53 [95% CI 0·32-0·87]; one-sided nominal p=0·0050), and fatigue scores (0·48 [95% CI 0·33-0·69]; one-sided nominal p<0·0001). INTERPRETATION: Pembrolizumab monotherapy led to clinically meaningful improvements in HRQOL compared with chemotherapy in patients with previously untreated microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer. These data, along with the previously reported clinical benefits, support pembrolizumab as a first-line treatment option for this population. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co, Kenilworth, NJ, USA.

Patients' willingness to reconsider cancer genetic testing after initially declining: Mention it again.

Patients at risk for hereditary cancer syndromes sometimes decline clinically appropriate genetic testing. The purpose of the current study was to understand what preferences, concerns, and desires informed their refusal as well as their current level of interest in being tested. We interviewed patients who had been seen in a hereditary cancer clinic at Vanderbilt University Medical Center and had declined genetic testing. In all, 21 in-depth, semi-structured qualitative interviews were conducted. Although patients provided many reasons for declining testing, they most often cited their psychosocial state at the time of the initial invitation to participate in genetic testing as their reason for refusal. The majority (67%) said that they either would or had changed their mind about testing if/when their clinicians 'mentioned it again'. Patients at risk for hereditary cancer who refuse testing at the time of genetic counseling may later change their mind. In particular, if a patient declines testing around the time of a major medical diagnosis or intervention, clinicians who are providing ongoing care may want to raise the topic afresh after the patient has had time to recover from initial distress related to diagnosis or treatment. Strategies to prompt clinicians to have these conversations are suggested.

How to facilitate psychosocial adjustment in women tested for hereditary breast or ovarian cancer susceptibility? Insights from network analysis.

BACKGROUND: Increasingly complex genetics counseling requires guidance to facilitate counselees' psychosocial adjustment. We explored networks of inter-relationships among coping strategies and specific psychosocial difficulties in women tested for hereditary breast or ovarian cancer. METHODS: Of 752 counselees consecutively approached, 646 (86%) completed questionnaires addressing coping strategies (Brief-COPE) and psychosocial difficulties (PAHC) after the initial genetic consultation (T1), and 460 (61%) of them again after the test result (T2). We applied network analysis comparing partial correlations among these questionnaire scales, according to the type of genetic test - single gene-targeted or multigene panel, test result and, before and after testing. RESULTS: Overall, 98 (21.3%), 259 (56.3%), 59 (12.8%) and 44 (9.6%) women received a pathogenic variant, uninformative negative (panel testing), variant of uncertain significance (VUS) or true negative (targeted testing) result, respectively. In most networks, connections were strongest between avoidance and general negative emotions. Cognitive restructuring was inter-related to lower psychosocial difficulties. Avoidance and familial/social relationship difficulties were strongly related in women receiving a pathogenic variant. Stronger inter-relationships were also noticed between avoidance and worries about personal cancer and concerns about hereditary predisposition in women receiving a VUS result. Differences in the prominence of inter-relationships were observed by type of testing and assessment time. CONCLUSIONS: Network analysis may be fruitful to highlight prominent inter-relationships among coping strategies and psychosocial difficulties, in women tested for HBOC susceptibility, offering guidance for counseling.

Germline Genetics and Childhood Cancer: Emerging Cancer Predisposition Syndromes and Psychosocial Impacts.

PURPOSE OF REVIEW: Germline genetic variants contribute to a substantial proportion of cases of cancer in childhood. The purpose of this review is to describe two emerging pediatric cancer predisposition syndromes, including published surveillance protocols, as well as the psychological impacts related to childhood cancer predisposition. RECENT FINDINGS: DICER1 syndrome is pleotropic, predisposing to a variety of tumors and likely phenotypically broader than currently realized. Rhabdoid tumor predisposition syndrome carries a risk for development of aggressive malignancies occurring in nearly any tissue. New pediatric hereditary cancer syndromes are likely to be identified as genetic evaluation evolves. Advantages and disadvantages of genetic testing and surveillance protocols need to be discussed with patients and families in a team-based approach, with the input of a genetic counselor holding expertise in pediatric cancer predisposition. Finally, literature on psychosocial impacts of hereditary cancer syndromes in pediatric patients is sparse, necessitating further research.

How I approach hereditary cancer predisposition in a child with cancer.

Approximately 10% of all children with cancer are affected by a monogenic cancer predisposition syndrome. This has important implications for both the child and her/his family. The assessment of hereditary cancer predisposition is a challenging task for clinicians and genetic counselors in daily routine. It includes consideration of tumor genetics, specific features of the patient, and the medical/family history. To keep up with the pace of this rapidly evolving and increasingly complex field of genetic susceptibility, we suggest a systematic approach for the evaluation of the child with cancer and her/his family by an interdisciplinary team specialized in hereditary cancer predisposition.

Experience Gained from the Development and Execution of a Multidisciplinary Multi-syndrome Hereditary Colon Cancer Family Conference.

Genetic healthcare professionals provide genetic cancer risk assessment and follow-up care for patients facing hereditary cancers. To meet the needs of those affected by hereditary colorectal cancer, City of Hope and the Hereditary Colon Cancer Foundation collaborated to develop a "Family Day" conference. We describe the development of our conference based upon the Hereditary Colon Cancer Foundation's "Family Day" program model, with refinements completed using the Participatory Action Research theoretical framework, which incorporated input from conference participants and researchers. Thirty-one participants attended the conference, representing patients with, or families, friends, and caregivers of those with, multiple colorectal cancer predisposition syndromes, including Lynch, familial adenomatous polyposis, and juvenile polyposis. Participants who completed the feedback surveys (n = 22) were highly satisfied with the presentation content, ranking the keynote lecture on family communication the highest of the conference events. Participants also provided feedback regarding how to improve future conferences. In conclusion, we share our experience and provide guidance for developing a successful hereditary colon cancer predisposition patient and family conference.

Development and pilot testing of a leaflet informing women with breast cancer about genomic testing for polygenic risk.

The inclusion of polygenic risk scores in breast cancer risk prediction models provides a more personalised and accurate prediction of breast cancer risk for women with and without breast cancer, who would otherwise receive negative results from traditional testing of moderate- and high-risk genes. This study aimed to develop, and pilot test a leaflet with a sample of women participating in a large prospective cohort study. The leaflet aimed to provide information about polygenic risk to assist women to decide whether or not to learn results from genomic testing for common risk variants associated with breast cancer risk. A prototype of the leaflet was developed based on published literature and with the expertise from a multidisciplinary team. The acceptability of the leaflet was assessed by self-report questionnaire among 29 women participating in the prospective cohort study. More than 80% participants stated that the leaflet was clear, informative and easy to understand and increased their understanding of polygenic risk information. While low to moderate levels of distress/worry were reported around implications of the test results for the next generation, 71% felt reassured and agreed that the information provided in the leaflet had helped them cope. Pilot-test results indicate the leaflet is acceptable to the participants and the revised leaflet can be used as an information tool for women undergoing genomic testing. This educational leaflet will become a useful information source to meet the information needs of women undergoing genomic testing.

"A change in perspective": Exploring the experiences of adolescents with hereditary tumor predisposition.

BACKGROUND: Hereditary tumor predisposition syndromes (HTPSs) are being recognized more frequently in the etiology of pediatric cancer. Previous research indicates that disclosure of tumor susceptibility is a significant event in adolescents' lives. Insight into adolescents' adjustment to knowledge of their syndromes can guide healthcare delivery, particularly genetic counseling. This study explored the experiences of adolescents with hereditary tumor predisposition and their perceptions of living at risk. METHODS: Seven adolescents, ages 14 to 17, representing six different childhood-onset HTPSs, were purposively sampled and interviewed using a study-specific semistructured interview guide. We explored the disclosure process, support systems, and the perceived benefits and harms of knowledge of hereditary tumor susceptibility. Interview transcripts were analyzed via interpretive description. RESULTS: Three major themes emerged from the data: (1) The benefits of knowledge outweigh the harms; (2) context surrounding genetic testing must be recognized; and (3) self-concept is influenced but not defined by tumor risk. CONCLUSIONS: We conclude that adolescents recognize the challenges associated with awareness of tumor predisposition but may also identify positive aspects in their experiences, reflecting a changed life perspective. Results of this exploratory study suggest strategies that can guide pretest and posttest genetic counseling of adolescents for HTPSs, facilitating the adaptive incorporation of genetic information into an adolescent's self-concept.

Quality-of-life implications of risk-reducing cancer surgery.

BACKGROUND: Modern advances in genetic sequencing techniques have allowed for increased availability of genetic testing for hereditary cancer syndromes. Consequently, more people are being identified as mutation carriers and becoming aware of their increased risk of malignancy. Testing is commonplace for many inheritable cancer syndromes, and with that comes the knowledge of being a gene carrier for some patients. With increased risk of malignancy, many guidelines recommend that gene carriers partake in risk reduction strategies, including risk-reducing surgery for some syndromes. This review explores the quality-of-life consequences of genetic testing and risk-reducing surgery. METHODS: A narrative review of PubMed/MEDLINE was performed, focusing on the health-related quality-of-life implications of surgery for hereditary breast and ovarian cancer, familial adenomatous polyposis and hereditary diffuse gastric cancer. RESULTS: Risk-reducing surgery almost uniformly decreases cancer anxiety and affects patients' quality of life. CONCLUSION: Although the overwhelming quality-of-life implications of surgery are neutral to positive, risk-reducing surgery is irreversible and can be associated with short- and long-term side-effects.

Reproductive Decision Support: Preferences and Needs of Couples at Risk for Hereditary Cancer and Clinical Geneticists.

For couples at high risk of transmitting a cancer predisposition to offspring, reproductive decision-making can be challenging. As the choice between available reproductive options is preference-sensitive, the use of a decision aid can support these couples in their decisional process. The present study aims to investigate preferences and needs of involved stakeholders regarding the development and implementation of a patient decision aid. Semi-structured interviews assessing the needs and preferences regarding the content and functionalities of a decision support program were conducted among seven couples at risk for hereditary cancer and among eight clinical geneticists involved in oncogenetic counseling. Many similarities were found between the expressed preferences and needs of both stakeholder groups concerning the content, barriers and facilitating factors regarding the use of the decision aid, and its implementation. Emphasis was placed on the use of simple non-medical language, an extensive explanation of the procedures and techniques used in prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD), and the role of health care providers to refer couples to the decision aid. Both stakeholder groups were in favor of incorporating narrative stories in the decision aid. Integrating the present findings with knowledge on reproductive decisional motives and considerations is essential in guiding the development of a decision aid that corresponds to the preferences and needs of end-users. TRIAL REGISTRATION: NTR5467.

Patients' Attitudes Towards Disclosure of Genetic Test Results to Family Members: The Impact of Patients' Sociodemographic Background and Counseling Experience.

Many factors predict the intention to disclose genetic information to relatives. The article examines the impact of patients' socio-demographic factors on their intention to disclose genetic testing results to their relatives. Data were collected in eight genetic clinics in Israel. Patients were requested to fill in a questionnaire after counseling. A convenience sample of 564 participants who visited these clinics was collected for a response rate of 85 %. Of them, 282 participants came for susceptibility testing for hereditary cancers (cancer group), and 282 for genetic screening tests (prenatal group). In the cancer group, being secular and having more years of education correlated positively with the intention to disclose test results to relatives. In the prenatal group, being married and female correlated positively with the intention to disclose. In the cancer group, being religious and with less years of education correlated positively with the view that the clinician should deliver the results to the family. In the prenatal group, being male and unmarried correlated positively with this belief. In both groups, being of young age correlated with the perception that genetic information is private. Varied sociodemographic factors affect the intention to inform family members. Thus, knowing the social background of patients will shed light on people's attitudes to genetic information and will help clinicians provide effective counseling in discussions with patients about the implications of test results for relatives.

Lifestyle Risk Factors Among People Who Have Had Cancer Genetic Testing.

Hereditary cancer genetic counseling often focuses on medically intensive risk-reduction strategies, like imaging and risk-reducing surgeries. Lifestyle factors also influence cancer risk, but health behavior counseling is not common in genetic counseling. Information about typical lifestyle risk factors among patients seeking hereditary cancer risk is sparse. The current study describes cancer risk-relevant lifestyle factors for people who have had cancer genetic testing. Data came from the Health Information National Trends Survey (HINTS 4) collected in 2013. Analytic variables represented American Cancer Society nutrition and physical activity guidelines. Lifestyle factors were assessed for people who had undergone testing for BRCA1, BRCA2, or Lynch Syndrome genes. Among 3016 HINTS respondents, 135 had cancer genetic testing. Of these, 58 % were overweight or obese. Eighteen percent reported no moderate-intensity physical activity. Average sedentary screen-time was 3.4 h (SE = 0.472) daily. Sixty-three percent drank non-diet soda, and 23 % of these people drank soda every day. Between 18 and 36 % consumed less than 2 ½ cups fruits/vegetables daily. Twenty-four percent were current smokers. Lifestyle risk factors were not different between people who had genetic testing and those who had not. In conclusion, most people who had genetic testing for cancer susceptibility have at least one modifiable risk factor. Genetic counselors have opportunities to impact a counselee's cancer risk not only through risk-tailored medical procedures, but also through lifestyle modification recommendations. Results of the current study may foster a broader discussion of genetic counselors' roles in healthy lifestyle education.

Challenges to clinical utilization of hereditary cancer gene panel testing: perspectives from the front lines.

Next generation sequencing (NGS) technology is rapidly being implemented into clinical practice. Qualitative research was performed to gain an improved understanding of the landscape surrounding the use of NGS in cancer genetics. A focus group was conducted at the Wisconsin Cancer Risk Programs Network biannual meeting. Free flowing discussion with occasional open-ended questions provided insights into the use of NGS. 19 genetic counselors and medical professionals participated. Three major themes were identified with respect to NGS and its use in cancer genetics: knowledge gaps, the evolving clinician role, and uncertain utility. Several corresponding subthemes were identified. With respect to knowledge gaps, participants expressed concern regarding unexpected results and variants of unknown significance, lack of data about NGS findings, absence of standardization regarding use of NGS and guidelines for interpretation, and discomfort with new technology. Regarding the evolving clinician role, necessary changes to the roles of genetic counselors and physicians were noted, as was the resultant impact on care received by patients and their families. Finally, the clinical and economic utility of NGS was questioned. While a shift from traditional Sanger sequencing to NGS is occurring in molecular genetic testing for disease susceptibility, there are several obstacles that need to be overcome before widespread adoption of this technology can occur. Furthermore, key aspects of NGS and it utility remain unexplored. Continued investigation into these subjects is necessary before this technology will consistently be of benefit to patients and their families.

Prevalence and detection of psychosocial problems in cancer genetic counseling.

Only a minority of individuals who undergo cancer genetic counseling experience heightened levels of psychological distress, but many more experience a range of cancer genetic-specific psychosocial problems. The aim of this study was to estimate the prevalence of such psychosocial problems, and to identify possible demographic and clinical variables associated significantly with them. Consenting individuals scheduled to undergo cancer genetic counseling completed the Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire, the Hospital Anxiety and Depression Scale (HADS) and the Distress Thermometer (DT) prior to or immediately following their counseling session. More than half of the 137 participants reported problems on three or more domains of the PAHC, most often in the domains 'living with cancer' (84%), 'family issues' (46%), 'hereditary predisposition' (45%), and 'child-related issues' (42%). Correlations between the PAHC, the HADS and the DT were low. Previous contact with a psychosocial worker, and having a personal history of cancer were associated significantly with HADS scores, but explained little variance (9%). No background variables were associated significantly with the DT. Previous contact with a psychosocial worker, and having children were significantly associated with several PAHC domains, again explaining only a small percentage of the variance (2-14%). The majority of counselees experience specific cancer genetic counseling-related psychosocial problems. Only a few background variables are associated significantly with distress or psychosocial problems. Thus we recommend using the PAHC or a similar problem-oriented questionnaire routinely in cancer genetic counseling to identify individuals with such problems.

Psychosocial aspects of hereditary cancer (PAHC) questionnaire: development and testing of a screening questionnaire for use in clinical cancer genetics.

BACKGROUND: Up to three-quarters of individuals who undergo cancer genetic counseling and testing report psychosocial problems specifically related to that setting. The objectives of this study were to develop and evaluate the screening properties of a questionnaire designed to assess specific psychosocial problems related to cancer genetic counseling. METHODS: We adopted the European Organisation for Research and Treatment of Cancer Quality of Life Group guidelines to develop the Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire, a 26-item questionnaire organized into six problem domains: genetics, practical issues, family, living with cancer, emotions, and children. The Distress Thermometer and a question per domain on the perceived need for extra psychosocial services were included as well. We administered the questionnaire and the Hospital Anxiety and Depression Scale to 127 counselees at the time of genetic counseling and 3 weeks after DNA test disclosure. As a gold standard to evaluate the screening properties of the questionnaire, participants underwent a semi-structured interview with an experienced social worker who assessed the presence and severity of problems per domain. RESULTS: A cutoff score representing responses of 'quite a bit' or 'very much' to one or more items within a given problem domain yielded moderate to high sensitivity across domains. A cutoff of 4 on the Distress Thermometer yielded high sensitivity. The questions regarding the perceived need for extra psychosocial services yielded high specificity and negative predictive values. CONCLUSION: The Psychosocial Aspects of Hereditary Cancer questionnaire in combination with the Distress Thermometer can be used as a first-line screener for psychosocial problems within the cancer genetic counseling setting.

Comparison of attitudes regarding preimplantation genetic diagnosis among patients with hereditary cancer syndromes.

Preimplantation genetic diagnosis (PGD) allows couples to avoid having a child with an inherited condition, potentially reducing cancer burden in families with a hereditary cancer predisposition. This study investigated and compared awareness and acceptance of PGD among patients with different hereditary cancer syndromes. Questionnaires were mailed to 984 adults with hereditary breast and ovarian cancer, Lynch syndrome, familial adenomatous polyposis, or multiple endocrine neoplasia type 1 or 2. Associations between clinical, demographic, and psychosocial factors and awareness and acceptance of PGD were examined. Of 370 respondents (38 % return rate), 28 % felt their syndrome impacted family planning, 24 % were aware of PGD, 72 % felt that PGD should be offered, 43 % would consider using PGD, and 29 % were uncertain. Family experience and syndrome-specific characteristics, such as disease severity, quality of life and availability of medical interventions as well as gender, family planning stage, and religiosity impact perceptions of the acceptability of PGD, though a high level of uncertainty exists. Hereditary cancer patients lack awareness of PGD despite feeling that PGD should be offered, highlighting the need for education on this topic. While we found attitudes about the acceptability of PGD to be generally similar to those reported in the literature and of genetics and ethics experts, we observed similarities and differences between syndromes that provide insight into why some hereditary cancer patients may find PGD more acceptable than others.

Practical aspects of genetic counseling in breast cancer: lights and shadows.

In unselected populations, less than 10% of breast cancers are associated with germline mutations in predisposing genes. Breast cancer type 1 and 2 (BRCA1 and BRCA2) susceptibility genes are the most common involved genes and confer a 10-30 times higher risk of developing the disease compared to the general population. A personal or family history suggestive of inherited breast cancer syndrome may be further evaluated to assess the risk of genetic predisposition and the presence of a genetic mutation. Breast cancer genetic counseling should include a careful risk assessment with associated psychosocial evaluation and support, possible molecular testing, personalized discussion of results. Knowledge of BRCA status can influence individualized cancer risk-reduction strategies. i.e. active surveillance, prophylactic surgery and/or pharmacoprevention.

Can we test for hereditary cancer at 18 years when we start surveillance at 25? Patient reported outcomes.

DNA-testing for BRCA1/2 or Lynch syndrome is possible from the age of 18 years, although surveillance usually starts at 25. Some patients regret their decision of testing before age 25. This retrospective study evaluates whether the testing age should be above 25 years to prevent adverse effects such as regret or decisional conflict, by determining the percentage and characteristics of patients reporting these problems. 111 of 219 patients (51%) tested for BRCA1/2 mutations or Lynch syndrome between 18 and 25 years from July 1996 to February 2011, returned self-report surveys. Primary measures were regret, decisional conflict and family influence. Secondary measures included quality of life (QoL), coping style, impact of genetic testing, and risk perception. Median age was 27 [21-40] years, with 86% female. 73% was tested for BRCA1/2, 27% for Lynch syndrome. Only 3% reported regret, however 39% had moderate (32%) to severe (7%) decisional conflict. Regression analysis revealed that decisional conflict was associated with more monitoring/neutral coping style (p < 0.03) or paternal/no family mutation (p < 0.02); there were no differences in QoL, impact or risk perception. 42% were mutation carriers, showing equal decisional conflict to non-carriers. 68% would recommend testing <25 years; 77% desired surveillance <25 years if a mutation carrier. Almost no patient tested for hereditary cancer between 18 and 25 years regretted this decision. A third reported retrospective decisional conflict, especially those actively seeking information when faced with a threat and/or those with a paternal or unknown inheritance. These patients may benefit from decisional support and personalized information.