Personal Family History Research Articles

Observational study of population genomic screening for variants associated with endocrine tumor syndromes in a large, healthcare-based cohort

BackgroundIn current care, patients’ personal and self-reported family histories are primarily used to determine whether genetic testing for hereditary endocrine tumor syndromes (ETS) is indicated. Population genomic screening for other conditions has increased ascertainment of individuals with pathogenic/likely pathogenic (P/LP) variants, leading to improved management and earlier diagnoses. It is unknown whether such benefits occur when screening broader populations for P/LP ETS variants. This manuscript assesses clinical utility outcomes of a large, unselected, healthcare-based genomic screening program by describing personal and family history of syndrome-related features, risk management behaviors after result disclosure, and rates of relevant post-disclosure diagnoses in patient-participants with P/LP ETS variants.MethodsObservational study of individuals informed of a P/LP variant in MEN1, RET, SDHAF2, SDHB, SDHC, SDHD, or VHL through Geisinger’s MyCode Community Health Initiative between June 2016 and October 2019. Electronic health records (EHRs) of participants were evaluated for a report of pre-disclosure personal and self-reported family histories and post-disclosure risk management and diagnoses.ResultsP/LP variants in genes of interest were identified in 199 of 130,490 (1 in 656) adult Geisinger MyCode patient-participants, 80 of which were disclosed during the study period. Eighty-one percent (n = 65) did not have prior evidence of the result in their EHR and, because they were identified via MyCode, were included in further analyses. Five participants identified via MyCode (8%) had a personal history of syndrome-related features; 16 (25%) had a positive self-reported family history. Time from result disclosure to EHR review was a median of 0.7 years. Post-disclosure, 36 (55.4%) completed a recommended risk management behavior; 11 (17%) were diagnosed with a syndrome-related neoplasm after completing a risk management intervention.ConclusionsBroader screening for pathogenic/likely pathogenic variants associated with endocrine tumor syndromes enables detection of at-risk individuals, leads to the uptake of risk management, and facilitates relevant diagnoses. Further research will be necessary to continue to determine the clinical utility of screening diverse, unselected populations for such variants.

Diagnostic difficulties in giant benign phyllodes tumor

Phyllodes tumors (PTs) are rare tumors of the breast, which encompass both stromal and epithelial components. The maximum incidence is in the fourth decade of life. Most of these tumors are benign, but about one third can be malignant acting as sarcomas. Due to their rarity and atypical clinical behavior (especially for the giant ones), the management of these tumors is usually difficult. We report a case of a 24-year-old woman who presented in the Department of Oncology for rapid increase in volume of the left breast. She had no personal pathological or family history. Initial clinical exam showed a large irregular mass in the left breast of approximately 30 cm and palpable lymph nodes in the ipsilateral axilla. A core needle biopsy for the tumor was performed with histopathological (HP) result that revealed an aspect suggesting fibroadenoma/PT. Contrast-enhanced computed tomography (CT) scan identified lymph node enlargement in the left axilla and a peripheral nodule in the lung about 5.5/3.4 mm with no specific features. The patient was then transferred to the Department of Surgery, where left mastectomy and axillary lymph node sampling were performed. HP result of the surgical specimens confirmed the presence of both fibroadenoma and PT, with clear margins above 1 cm, but recommended immunohistochemistry (IHC) to clearly specify benign versus borderline type. Five lymph nodes out of six resected presented microscopic reactive changes. We performed a search of literature using the keywords “giant”, “benign” and “phyllodes”. The results were used to summarize and discuss some of the main features of this type of tumors as well as diagnostic and therapeutic difficulties.

Correlations between alexithymia, emotional instability, autism spectrum disorder and eating disorders: analysis of a case

IntroductionEating disorders and borderline personality disorder can coexist with high frequency in people with alexithymia. At the same time, it has been described that alexithymia can be present in patients suffering from depression, anxiety, obsessive-compulsive disorders, PTSD and eating disorders, among others. In this sense, it has been described that alexithymia could help maintain eating disorder.ObjectivesTo review the existing literature on the relationship between alexithymia, emotional instability and a family history of autism spectrum traits with the development of eating disorders. To expose, through the clinical case of a patient with eating disorders, the diagnostic complexity and evolution after the beginning of a comprehensive and multidisciplinary therapeutic plan with different mental health devices.MethodsTo review the personal and family psychopathological aspects and the clinical evolution of a patient with a diagnosis of restrictive subtype anorexia nervosa since its inclusion in a therapeutic program.ResultsThis is a longitudinal study through personal biographical reconstruction and family history and subsequent follow-up of a clinical case based on the implementation of an individualized therapeutic program and the results obtained.ConclusionsCurrently there is evidence in the literature that finds a high correlation between alexithymia and eating disorders. However, these findings are believed to be influenced by other comorbid symptoms such as depression or anxiety. Furthermore, the diagnosis of ASD in people with AN is a complex process that requires a thorough clinical evaluation over time. Detailed studies are needed to determine the importance of these factors in the development of an eating disorder.DisclosureNo significant relationships.

Insights Into Sibling Relationships and Longevity From Genetics of Healthy Ageing Nonagenarians: The Importance of Optimisation, Resilience and Social Networks.

Understanding how to “Age Longer and Age Well” is a priority for people personally, for populations and for government policy. Approximately ten percent of nonagenarians reach 90 years and beyond in good condition and seem to have a combination of both age-span and health-span. However, the factors which contribute to human longevity remain challenging. Culture is a shared system of learning ideas, feelings, and survival strategies. It has a strong influence on each person’s psychological development, behavior, values and beliefs. Nonagenarians have rich life experiences that can teach us much about aging well; they are rich reservoirs of genetic, lifestyle and psychological information which can help understanding about how to live longer and better. Sibling or trio nonagenarians are important sources of family beliefs and behaviors upon which individual personalities may have been built. Their personal family histories and narratives are powerful tools that help to determine familial traits, beliefs and social behaviors which may help establish factors important in the siblings’ longevity. Using purposefully selected subjects, recruited to the Genetics of Healthy Ageing (GeHA) project in four European countries, this research used the simple life story and qualitative research methods to analyze contrasting and distinctive questions about the interface between the psychological and social worlds as presented in the nonagenarian siblings’ insights about their longevity. Their stories aimed to give better understanding about which psychological aspects of their common life journey and the degree of emotional support in their sibling relationships may have supported their paths to longevity. The most universal finding in each of the four European countries was that nonagenarians demonstrated high positivity, resilience and coping skills and were supported in social networks. Around this theme, nonagenarians reported “being happy,” “always cheerful,” “never melancholy” and having a contentment with a “rich life” and family relationships which fits with accumulating evidence that life satisfaction comes from a perceived self-efficacy and optimism. Most sibling relationships in this study, when analyzed according to the Gold classification, fit the “congenial” or “loyal” relationship type – demonstrating a healthy respect for the others’ opinion without overt dependence, which may help individual coping and survival mechanisms.

The role of familial predisposition in imaging-confirmed atraumatic rotator cuff tears.

The etiology of atraumatic rotator cuff tears is not completely understood. Limited data suggest the role of genetic and familial predisposition in the etiology of rotator cuff tears. The purpose of this study was to assess whether there is an increased likelihood of rotator cuff tears in family members of patients with rotator cuff tears vs. those without tears. This would provide evidence for whether there is an association between familial predisposition and rotator cuff tearing. Patients presenting to a shoulder clinic were recruited in this study. They provided information on personal medical history, shoulder symptoms, and family history of rotator cuff tears. The diagnosis of rotator cuff tears was based on imaging (magnetic resonance imaging or computed tomography arthrogram) confirmation of a structural defect in the rotator cuff. The association between family history of rotator cuff problems and the likelihood of an imaging-confirmed rotator cuff tear diagnosis was evaluated using multivariate logistic regression, adjusting for age, sex, race/ethnicity, cigarette smoking, hypertension, diabetes, and depression. In our cohort of 2335 patients, 52.6% (n = 1229) of patients had a rotator cuff tear. Among patients with tears, 17.9% (n = 220) of patients reported a family history of rotator cuff issues vs. 11.1% (n = 123) in patients without tears. A family history of rotator cuff problems was significantly associated with the diagnosis of an imaging-confirmed rotator cuff tear (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.71, 2.95). Other confounding variables such as increasing age (OR 1.06, 95% CI 1.05, 1.07) and Hispanic race/ethnicity as compared to non-Hispanic white race/ethnicity (OR 1.48, 95% CI 1.07, 2.05) were significantly associated with rotator cuff tears. Sex, smoking, hypertension, diabetes, and depression were not significantly associated with rotator cuff tearing. Our study shows that individuals with rotator cuff tears were more than 2 times as likely to have a family member with a tear as compared to patients without tears. Increasing age and patients who identified as being of Hispanic ancestry were also significantly associated with higher odds of rotator cuff tears.

Malnourishment Among Medical Students of Punjab. Is Underweight Status A Significant Issue in Pakistan?

Background: Assessment of the prevalence and factors which make a medical student of Public sector medical college of Punjab, Underweight.
 Methods: A cross-sectional study was conducted at 12 different medical colleges of the public sector in Punjab. A total of 352 students from all five years of the academic course participated in this study. A pre-tested structured questionnaire was distributed to the students after taking their consent. The data included demographic information, targeted questions on diet, personal health habits, illnesses, and family history.
 Results: Out of the total population, 28.1% were male and 71.9% were female students. The median age was 21.0 years. The mean weight was 59.2 ± 11.54 kgs. 56.3% of the students were hostelites and 43.8% were day-scholars. The average pocket-money of the students was 10150 Rs. Per month. According to body-mass index, about 11.9% students were underweight, 12.8% were overweight, 2.3% were obese, and 62.5% were of normal weight. Students who were underweight did not take the recommended daily number of calories. Among the causative factors, a significant relation was also found between underweight status and mode of commute, hours of sleep, pocket money, and whether the student takes nutritional supplements or not. Relation with various symptoms including fatigue, headache, breathlessness, and insomnia was not significant.
 Conclusion: An alarming number of Underweight students was present in the Public sector medical colleges of Punjab, with the Underweight status being associated with a poor dietary status, unfavorable travel methods, and not taking nutritional supplements.

An Unusual Case of Gastrointestinal Polyposis

Question: A 55-year-old man presented our hospital with a 5-month history of nausea, dysgeusia, anorexia, hypoesthesia of the fingers, and a 10-kg weight loss. The patient’s personal medical history and family history were unremarkable. Careful physical examination revealed slight alopecia of the scalp, mild onychodystrophy of the finger nails and toenails, hyperpigmentation on the forehead, and brown, pigmented skin macules over the left calf (Figure A). Laboratory investigations disclosed albumin level of 35.3 g/L (reference range, 40–55 g/L), immunoglobulin M level of 0.192 g/L (reference range, 0.4–2.3 g/L), and 25-hydroxyvitamin D3 level of 18.5 ng/mL (reference range, 30–100 ng/mL).

Neural response to rewarding social feedback in never-depressed adolescent girls and their mothers with remitted depression: Associations with multiple risk indices.

Prevention of depression requires a clear understanding of etiology. Previous studies have identified reduced neural responses to monetary reward as a risk factor for depression, but social reward processing may be particularly relevant to depression. This study investigated associations between neural responses to social reward and three well-established risk factors for depression: personal history, family history, and interpersonal stress. We examined the reward positivity (RewP), an event-related potential sensitive to rewarding feedback, in a sample of 85 women with and without remitted depression and their never-depressed adolescent daughters. In never-depressed daughters, maternal history of depression predicted a blunted social RewP, but interpersonal stress did not. In the mothers, greater interpersonal stress predicted a blunted RewP, but personal depression history was not significant. Combined, these data suggest that personal history, family history, and interpersonal stress may converge on social reward sensitivity, which may advance future research to understand the development of depression. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Evaluating the Effectiveness of a Telehealth Cancer Genetics Program: A BRCA Pilot Study

Introduction: Ashkenazi Jewish (AJ) individuals face a 1 in 40 (2.5%) risk of having a BRCA mutation, which is 10 times the general population risk. JScreen launched the PEACH BRCA Study, a telehealth-based platform for BRCA education and testing, with the goal of creating an effective model for BRCA testing in low-risk AJ individuals who do not meet national testing criteria. Other goals were to determine the rate of BRCA mutations in this group, to assess the adequacy of screening for the 3 common AJ founder mutations only, and to assess satisfaction with the telehealth model to help inform a national launch of a broader cancer genetic testing program. Methods: Criteria for participation included those who were AJ, resided in the metro-Atlanta area, were aged 25 and older, and had no personal or close family history of BRCA-related cancers. Pre-test education was provided through a video and written summary, followed by complimentary BRCA1/2 sequencing and post-test genetic counseling. Participants responded to pre- and post-test surveys, which assessed knowledge and satisfaction. Those who were not eligible to participate were sent genetic counseling resources and later surveyed. Results: Five hundred one participants were tested and the results included 4 positives (0.8% positivity rate), 494 negatives, and 3 variants of uncertain significance. Overall satisfaction with the study process was high (96.9/100), knowledge about BRCA was high (97.5% of participants passed a pre-test knowledge quiz), and satisfaction with pre- and post-test education was high (97.9% of participants were satisfied with the pre-test video and written summary, and 99.5% felt that their post-test genetic counseling session was valuable). Many participants expressed interest in receiving broader cancer testing. Conclusions: The BRCA founder mutation rate in a low-risk AJ population was significantly lower than the previously established AJ rate of 1 in 40. It was also determined that a telehealth model for a cancer genetics program is effective and acceptable to the population tested. This study established interest in broader cancer genetic testing through a telehealth platform and suggested that testing may be successful in the Jewish community at a national level and potentially in other populations, provided that patient education and genetic counseling are adequately incorporated.

Knowledge and Practices of Female Teachers about Gestational Diabetes in Jizan Province, Saudi Arabia

Aim of Study: To assess the knowledge and practices of female teachers in Jizan Province about gestational diabetes (GD), and to identify factors associated with poor knowledge and practices related to the prevention of GD. Methods: This study followed an analytical cross-sectional research design conducted in Jizan Province, Saudi Arabia. A total of 300 female teachers were included. The inclusion criteria were being a married, Saudi female teacher, aged 20-52 years, who has at least one-year experience in Jizan Province at the start of data collection, with at least one child. An electronic on-line questionnaire was developed by the researchers. The study questionnaire included participants’ personal characteristics, past and family histories of GD and/or diabetes mellitus, in addition to questions to assess their knowledge and practices regarding GD. Results: The study included 300 female teachers. Their main knowledge gaps about GD were related to timing for screening (58.3%), necessary investigations (50%), its management (31.7%) and repeated pregnancies as a risk factor (24.3%). Participants’ healthy practices were physical exercise (53.3%), maintaining a healthy diet (66.7%) and following a diet to prevent being overweight (66.7%). Healthy practices during pregnancy included checking blood sugar (71%), watching body weight gain (74.7%) and keeping on healthy diets (83.7%). More than one-quarter of participants (29.7%) had poor knowledge, while 34% had poor practices. Participants’ knowledge levels differed significantly according to their qualification levels (p=0.048), having a family member working in the healthcare field (p=0.035), being currently diabetic (p=0.006), having a past history of GD (p<0.001), and having a positive family history of GD (p=0.005). Participants’ practice levels differed significantly according to their residence (p=0.012), experience in teaching (p=0.028), and having a family member in the healthcare field (p=0.002). Participants’ practice levels differed significantly according to being currently diabetic (p=0.011). Conclusions: Female teachers’ knowledge and practices about GD in Jizan Province are suboptimal. Female teachers’ knowledge is better among more experienced teachers, those with a higher level of education, in addition to diabetic teachers and those with a family history of diabetes. More experienced teachers, and those with a family history of the GD have the highest level of good practices. The most frequent sources for teachers of information about GD are relatives/friends. Key Words: Gestational diabetes, diabetes mellitus, knowledge, practices, teachers

Factors determining state of being overweight among the students of Government Medical Colleges of Punjab, Pakistan.

Objectives: To determine the prevalence and factors that make medical students of public sector colleges of Punjab, Overweight. Study Design: Cross-sectional study. Settings: 12 different medical colleges of the government sector in Punjab, Pakistan by both online and physical survey using non-probability convenient type of sampling. Period: January 2020 to February 2020. Material & Methods: A total of 352 students from all five years of the academic course participated in this study. A pre-tested structured questionnaire was self-administered to the students after taking their consent. The data included demographic information, targeted questions on diet, personal health habits, illnesses, and family history. The data was analyzed by the statistical program SPSS version 21. Results: Out of the total population, 28.1% were male and 71.9% were female students. The median age was 21.0 years. The mean weight was 59.2 ± 11.54 kgs. 56.3% of the students were hostelites and 43.8% were day-scholars. The average pocket-money of the students was 10,150 PKR Per month. According to the body-mass index, about 11.9% of students were underweight, 12.8% were overweight, 2.3% were obese, and 62.5% were of normal weight. It was found that females were more likely to be overweight than males. Not following any specific diet appeared to be the cause of being overweight while following specific diets was a protective factor against overweight status. Year of study, accommodation status, meals per day, calorie intake, ceremonial eating, hours of sleep, and study had no effect on overweight. Overweight students did not have a significant family history of diabetes mellitus. Conclusions: Poor dietary habits and unhealthy lifestyles increase the prevalence of overweight status among medical students and pose them at increased risk of serious illness in the future. Nutritional counseling and healthy lifestyle awareness are recommended for better practice of health and learning among medical students.

Impact of Variant Reclassification in Cancer Predisposition Genes on Clinical Care

Genetic testing has clinical utility in the management of patients with hereditary cancer syndromes. However, the increased likelihood of encountering a variant of uncertain significance in individuals of non-European descent such as Asians may be challenging to both clinicians and patients. This study aims to evaluate the impact of variant reclassification in an Asian country with variants of uncertain significance reported in cancer predisposition genes. A retrospective analysis of patients seen at the Cancer Genetics Service at the National Cancer Centre Singapore between February 2014 and March 2020 was conducted. The frequency, direction, and time to variant reclassification were evaluated by comparing the reclassified report against the original report. A total of 1,412 variants of uncertain significance were reported in 49.9% (845 of 1,695) of patients. Over 6 years, 6.7% (94 of 1,412) of variants were reclassified. Most variants of uncertain significance (94.1%, 80 of 85) were downgraded to benign or likely benign variant, with a smaller proportion of variants of uncertain significance (5.9%, 5 of 85) upgraded to pathogenic or likely pathogenic variant. Actionable variants of uncertain significance upgrades and pathogenic or likely pathogenic variant downgrades, which resulted in management changes, happened in 31.0% (39 of 126) of patients. The median and mean time taken for reclassification were 1 and 1.62 year(s), respectively. We propose a clinical guideline to standardize management of patients reported to have variants of uncertain significance. Management should be based on the patient's personal history, family history, and variant interpretation. For clinically relevant or suspicious variants of uncertain significance, follow-up is recommended every 2 years, as actionable reclassifications may happen during this period.

VP26.08: Vein of Galen aneurysmal malformation

Vein of Galen aneurysmal malformation is a rare complex malformation of the cerebral vascular system, characterised by the dilation of an embryonic vein precursor of the Galenian vein causing an arteriovenous shunt. It is developed in the embryonic period, sporadic, more common for male fetus. This vascular malformation is detected only half of times before birth, it often increases in size with advancing age and is associated with hydrocephalus, seizures, intracranial hemorrhage, heart failure and even resultant death. So early diagnosis and treatment is important in order to avoid such consequences. We report the case of a 31-year-old pregnant woman of 26 weeks, primiparous, with no obstetric or personal family history of interest. We found, at the second trimester morphological ultrasound, a cerebral vascular dilatation using the colour and pulsed Doppler which was isolated with no other cerebral or other organ malformations. First trimester ultrasound and serum markers were normal. Subsequently, a magnetic resonance was performed confirming the diagnosis. the pregnancy was carried to term with delivery by Caesarean section. Physical examination of the baby was unremarkable. The baby was called for post-natal evaluation at the radiology department on the second day and was scheduled for radiological embolisation of the aneurysm, the newborn died after that intervention. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

The association between lichen planus and hepatitis C virus infection: A case control study

Background: The incidence of Hepatitis C virus (HCV) infection among patients with Lichen planus (LP) varies considerably. There is also lack of data in Indian population. Due to these variation, this study is to assessing the prevalence of HCV infection among patients with CLP in Hassan Karnataka. Methods: 135 clinically diagnosed cases of Lichen planus more than 18 years of age will be included as cases.147 patients having skin diseases other than lichen planus will be included as controls. Details of the patients personal history and family history,medical history and blood transfusion history will be collected. Detection of antibodies against HCV (anti-HCV) by enzyme-linked immunosorbent assay (ELISA). Results: Anti-HCV antibodies were found in 3(2.2%) patients of the case group and 1(0.7%) in control group. P value is 0.274, not statistically significant. Conclusion: Currently, there is no evidence confirming the relationship between HCV infection and CLP in Hassan Karnataka. However, there is a need for further research on larger groups of

Relationship Between Concomitant Atopic Diseases With Atopic Dermatitis Severity And Persistence.

Introduction: The atopic march consists of atopic dermatitis (AD), allergic rhinitis or sinusitis (AR), allergic conjunctivitis (AC) and bronchial asthma (BA). The influence of concomitant atopic diseases on AD is under-explored. We determined the relationship between personal and family history of atopic diseases with AD severity and persistence. Methods: A cross sectional study involving AD patients was performed at dermatology clinics of two tertiary hospitals. Inclusion criterion was all patients diagnosed with AD. Demographic data, personal and family history of atopy (BA, AR and AC) were obtained by face-to-face interview. AD severity was evaluated using Investigator’s Global Assessment (IGA). AD was considered persistent if continued beyond age 12 years. Results: Sixty patients aged 21.6±17.2 participated. There were 25(41.7%) with concomitant AR, 16(26.7%) BA and 12(20%) AC. Forty seven (78.3%) patients had family history of atopy, 25(41.7%) had eczema, 24(40%) AR, 19(31.7%) BA and 2(3.3%) AC. Patients with BA [OR=3.8, 95%CI 1.04 to 14.4)], BA and AR [OR=9.74, 95%CI 1.13 to 83.67) and family history of BA [OR= 4.00, 95%CI 1.20 to 13.27) were more likely to exhibit moderate-severe AD. Personal AR, AC and family history of AD and BA were significantly more prevalent in patients with persistent AD. Conclusions: AR was the most common atopic disease associated with AD. Family history of eczema and AR were common. Personal BA, BA with AR and family history of BA were predictors of severe AD. Personal AR, AC and family history of AD and BA were associated with AD persistence.

Clinical, Molecular and Genetic Characteristics of Early Onset Gastric Cancer: Analysis of a Large Multicenter Study.

Simple SummaryGastric cancer is one of the most common cancers worldwide, showing high mortality rates. A small portion of gastric cancer patients, known as early onset gastric cancer (EOGC) patients, develop the disease before age 50, and their characteristics are poorly described. Thus, our main objective was to describe the clinical, molecular, and genetic characteristics of EOGC in a large multicenter cohort of patients. We were able to identify that most EOGC cases have similar characteristics: diagnosed at advanced stage, diffuse type, and infrequent DNA mismatch repair somatic deficiency. Although familial aggregation of gastric cancer was uncommon, a germline genetic mutation was identified in 25% of the patients tested. Our results show that EOGC has a marked genetic heterogeneity. Thus, it is essential to consider familial history of tumors, not only GC, in order to select adequate patients to perform a suitable genetic counseling and enhance the emerging use of multigene panels. Gastric adenocarcinoma (GC) is a common tumor with high morbidity and mortality. Only 7% of patients with GC are diagnosed before age 50 (early onset gastric cancer (EOGC)), and their characteristics have been poorly described. We aimed to describe clinical, molecular, and genetic characteristics of EOGC. A total of 309 patients with EOGC were retrospectively studied in four Spanish centers. Personal information, family history, and tumor information were registered. Germinal genetic analysis was performed in patients who met current criteria of a hereditary syndrome at the time of diagnosis. The median age at diagnosis was 44 years. The majority (73.3%) of tumors were diffuse, and 78.3% were diagnosed in an advanced stage. Familial aggregation of GC was present in 18/117 (15.4%) cases, and 5/117 (4.3%) met criteria for familial GC. MMR-IHC was performed in 126/309 (40.7%) tumors: 4/126 (3.1%) had loss of expression in MLH1/PMS2, without an associated germline mutation. Sixteen germline genetic analyses were performed, detecting a pathogenic variant in four (25%) cases: one in BRCA2, one in TP53, and two in CDH1. Most EOGC are diffuse and diagnosed in an advanced stage. In these patients, DNA MMR system deficiency is uncommon. Although familial aggregation was observed in only 15% of cases, a germline mutation was found in 25% of patients tested with clinical criteria. This demonstrates that EOGC has a marked genetic heterogeneity, reinforcing the importance of an accurate genetic counseling and enhancing the emerging use of multigene panels.

Variant reclassification and its impact on clinical care in an Asian cancer center.

10583 Background: Genetic testing has demonstrated clinical utility in the identification and subsequent surveillance of patients with cancer predisposition syndromes. However, the increased likelihood of encountering a variant of uncertain significance (VUS) in individuals of non-European descent such as Asians may be challenging to both clinicians and patients in interpretation and management. VUS can be reclassified as more data becomes available. VUS reclassification is important, as it may have implications for surveillance and treatment. This study aims to evaluate the prevalence and patterns of variant reclassification in an Asian country and its impact on patient management. Methods: A prospective cohort of patients seen at the Cancer Genetics Service at the National Cancer Center Singapore between February 2014 to March 2020 was evaluated. The frequency, direction and time to variant reclassification was assessed by comparing the reclassified report against the original report. Results: A total of 1412 VUS were reported in 49.9% (845/1695) of patients. Over six-years, 6.7% (94/1412) of variants were reclassified. Most VUS (94.1%; 80/85) were downgraded to benign/likely benign variant, with a smaller proportion of VUS (5.9%; 5/85) upgraded to pathogenic/likely pathogenic variant. Actionable VUS upgrades and pathogenic/likely pathogenic variant downgrades, that resulted in management changes, happened in 31.0% (39/126) of patients. The median and mean time taken for reclassification were 1 and 1.62 year(s) respectively. Conclusions: Clinicians need to put in place a system for review of variants, as variant reclassification can lead to changes in management in nearly 1/3 of patients. Management should be based on the patient’s personal history, family history and variant interpretation. We propose a clinical guideline to standardize management of patients with VUS. For clinically relevant or suspicious VUS, follow-up is recommended every two years, as actionable reclassifications may happen during this period.

Global tissue stiffness on breast MR elastography: High-risk dense breast patients have higher stiffness compared to average-risk dense breast patients.

10541 Background: Biomechanical tissue properties may vary in the breasts of patients at elevated risk for breast cancer. We aim to quantify in vivo biomechanical tissue properties in various breast densities and in both normal risk and high risk women using Magnetic Resonance Imaging (MRI)/MRE and examine the association of biomechanical properties of the breast with cancer risk. Methods: In this IRB–approved prospective single-institution study, we recruited two groups of women differing by breast cancer risk to undergo a 3.0 T dynamic contrast enhanced MRI/MRE of the breast. Low-average risk women were defined as having no personal or significant family history of breast cancer, no prior high risk breast biopsies and a negative mammography within 12 months. High-risk breast cancer patients were recruited from those patients who underwent standard of care breast MR. Within each breast density group (non-dense versus dense), two-sample t-tests were used to compare breast stiffness, elasticity, and viscosity across risk groups (low-average vs high). Results: There were 50 low-average risk and 86 high-risk patients recruited to the study. The risk groups were similar on age (mean age = 55.6 and 53.6 years), density (68% vs. 64% dense breasts) and menopausal status (66.0% vs. 69.8%). Among patients with dense breasts, mean stiffness, elasticity, and viscosity were significantly higher in high risk patients ( N = 55) compared to low-average risk patients ( N = 34; all p < 0.001). In the multivariate logistic regression model, breast stiffness remained a significant predictor of risk status (OR=4.26, 95% CI [1.96, 9.25]) even after controlling for breast density, MRI BPE, age, and menopausal status. Similar results were seen for breast elasticity (OR=4.88, 95% CI [2.08, 11.43]) and viscosity (OR=11.49, 95% CI [1.15, 114.89]). Conclusions: Structurally-based, quantitative biomarker of tissue stiffness obtained from global 3D breast MRE is associated with differences in breast cancer risk in dense breasts. As such, tissue stiffness could provide a novel prognostic marker to help identify the subset of high-risk women with dense breasts who would benefit from increased surveillance.[Table: see text]

Family History and Searching for Hidden Trauma—A Personal Commentary

Background: Searching family history is now popular through increased internet access coinciding with a need for understanding identity. Prior unresolved war trauma can help explain impacts on subsequent generations and the need to search for family narrative, particularly in refugee families. This paper explores the search for trauma narratives through personal family history research, with links to community groups. Method: The author’s own Polish family history research provides examples of trauma and loss from World War II in Poland. This is supplemented by quotes from an existing interview study of second-generation Poles to amplify themes and indicate their wider community relevance.

Informing Women About Overdetection in Breast Cancer Screening: Two-Year Outcomes From a Randomized Trial.

BackgroundSupporting well-informed decisions about breast cancer screening requires communicating that inconsequential disease may be detected, leading to overdiagnosis and overtreatment. Having previously shown that telling women about overdetection improved informed choice, we investigated effects on screening knowledge and participation over 2 years.MethodsWe conducted a community-based, parallel-group, randomized controlled trial in Australia. Participants were women aged 48-50 years, without personal or strong family history of breast cancer, who had not undergone mammography in the past 2 years. We randomly assigned 879 women to receive the intervention decision aid (evidence-based information on overdetection, breast cancer mortality reduction, and false-positives) or control decision aid (identical but without overdetection information). We interviewed 838 women postintervention and recontacted them for follow-up at 6 months and 1 and 2 years. Main outcomes for this report are screening knowledge and participation.ResultsWe interviewed 790, 746, and 712 participants at 6 months, 1, and 2 years, respectively. The intervention group demonstrated superior knowledge throughout follow-up. After 2 years, conceptual knowledge was adequate in 123 (34.4%) of 358 women in the intervention group compared with 71 (20.1%) of 354 control participants(odds ratio = 2.04, 95% confidence interval = 1.46 to 2.85). Groups were similar in total screening participation (200 [55.1%] vs 204 [56.0%]; = 0.97, 95% confidence interval = 0.73 to 1.29).ConclusionsA brief decision aid produced lasting improvement in women’s understanding of potential consequences of screening, including overdetection, without changing participation rates. These findings support the use of decision aids for breast cancer screening.