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Purpose: To describe the association between geographic location of residence and use of aneuploidy screening or prenatal genetic counseling and how it is modified by maternal race and ethnicity., Methods: Retrospective cohort of individuals at a tertiary care center between 2017-2019. County of residence was classified as rural or metropolitan based in US Office of Management and Budget 2019 definitions. Maternal race and ethnicity were self-identified. Our composite outcome was defined as use of aneuploidy screening or genetic counseling visit. The composite outcome was compared by geographic location and ethnicity. Logistic regression was used to model the relationship between geographic location and the composite outcome., Results: A total of 8774 pregnancies were included. Of these, 4770 (54%) had genetic screening, and 3781 (43%) had at least 1 genetic counseling visit. Rural patients were significantly less likely to have the composite outcome compared with metropolitan peers (37.1% vs 47.2%, P < .001). In addition, we identified differences in the composite outcome between White rural patients and LatinX rural patients (37.7% vs 35.6%, P < .001) and between Asian rural patients and LatinX and Black rural patients (41.0% vs 35.6%, P < .001; 41.0% vs 36.8%, P < .001). Logistic regression demonstrated that rural patients were significantly less likely to have the composite outcome compared with metropolitan peers, after adjusting for LatinX ethnicity and gestational age at first prenatal visit (OR 0.72, [0.55, 0.95], P = .002)., Conclusion: Rural, minority patients were significantly less likely to receive reproductive genetic services compared with metropolitan peers extending our knowledge of disparities in maternity care., Competing Interests: Conflict of Interest Asha N. Talati receives research support from the National Institutes of Health, Billion to One, and The Greenwall Foundation. Divya P. Mallampati receives salary support from the Department of Health and Human Services. Neeta L. Vora receives research support from National Institutes of Health and received supplies in kind from Illumina unrelated to this research., (Copyright © 2024. Published by Elsevier Inc.)

Cincinnati Children's Hospital Medical Center (CCHMC) implemented a Genetic Counseling Clinic (GCC), where the appointment for a general genetics indication is conducted solely by a genetic counselor (GC). We conducted a retrospective chart review of 211 patient encounters scheduled in the GCC between January 1, 2022 and June 30, 2022 and collected patient demographics, wait time, appointment characteristics, referral indication, and clinical recommendations. To study impact on patient access, we compared patient demographics and appointment characteristics with 912 patient encounters scheduled in the General Genetics Clinic with a geneticist during the same time period. We found that there were not significant differences in patient demographics scheduled in the GCC as compared with the General Genetics Clinic with the exception of insurance type, where patients scheduled in the GCC were more likely to have private insurance. Patients scheduled in the GCC had a significantly shorter wait time, were more likely to complete their appointment, were more often new to the genetics division, and were more likely to be seen via telehealth (audio plus video or audio-only) as compared with patients scheduled in the General Genetics Clinic. The most common indications for patients scheduled in the GCC were post-test counseling (36.0%) followed by pre-test counseling and coordination of testing (22.3%), and first-line testing for autism, intellectual disability, and developmental delay (13.7%). Completed appointments in the GCC often resulted in the GC ordering genetic testing (67.5%). After genetic testing results were received, most patients (72.7%) did not require subsequent follow-up with the genetics division, thereby reducing burden to the medical genetics team. Our GCC increased access to genetic services and allowed GCs and clinical geneticists to better work at the top of their scope of practice., (© 2023 National Society of Genetic Counselors.)

Importance: Between 5% and 10% of breast cancer cases are associated with an inherited germline pathogenic or likely pathogenic variant (GPV) in a breast cancer susceptibility gene (BCSG), which could alter local and systemic therapy recommendations. Traditional genetic testing criteria misses a proportion of these cases., Objective: To evaluate the prevalence and clinicopathological associations of GPVs in 2 groups of BCSGs among an ethnically diverse cohort of women with newly diagnosed breast cancer., Design, Setting, and Participants: This cross-sectional study, conducted at 3 Montreal hospitals between September 2019 and April 2022, offered universal genetic counseling and testing to all women with a first diagnosis of invasive breast cancer. Women were offered an obligatory primary panel of BRCA1, BRCA2, and PALB2 (B1B2P2) and an optional secondary panel of 14 additional BCSGs. Eligible participants were women 18 years of age or older who received a diagnosis of a first primary invasive breast cancer not more than 6 months before the time of referral to the study. Data were analyzed from November 2023 to June 2024., Results: Of 1017 referred patients, 805 were eligible and offered genetic counseling and testing, and 729 of those 805 (90.6%) consented to be tested. The median age at breast cancer diagnosis was 53 years (range, 23-91 years), and 65.4% were White and of European ancestry. Fifty-four GPVs were identified in 53 patients (7.3%), including 39 patients (5.3%) with B1B2P2 and 15 patients (2.1%) with 6 of the 14 secondary panel BCSGs (ATM, BARD1, BRIP1, CHEK2, RAD51D, and STK11). On multivariable analysis, clinical factors independently associated with B1B2P2-positive status included being younger than 40 years of age at diagnosis (odds ratio [OR], 6.83; 95% CI, 2.22-20.90), triple-negative breast cancer (OR, 3.19; 95% CI, 1.20-8.43), high grade disease (OR, 1.68; 95% CI, 1.05-2.70), and family history of ovarian cancer (OR, 9.75; 95% CI, 2.65-35.85). Of 39 B1B2P2-positive patients, 13 (33.3%) were eligible for poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors., Conclusions and Relevance: In this cross-sectional universal genetic testing study of women with newly diagnosed invasive breast cancer, the prevalence of GPVs was 7.3%, with 5.3% of patients testing positive for B1B2P2. Among B1B2P2-women women, one-third were eligible for PARP inhibitors.

Background: Currently, racial disparities exist in access to genetic testing. Recent developments have helped narrow the gap in accessibility. The purpose of this study was to determine whether racial disparities in genetic consultation attendance and completion of genetic testing persist, and, if so, factors that contribute to under-utilization of these resources., Methods: A single-institution retrospective review of breast patients referred for genetic counseling between 2017 and 2019 was performed. Univariate and multivariate logistic regression evaluated factors associated with genetic counseling attendance and genetic testing., Results: A total of 596 patients were referred for genetic counseling: 433 (72.7%) white; 138 (23.2%) black; and 25 (4.2%) other or unknown. In multivariate analysis, black patients, patients without breast cancer family history, and patients without a current cancer diagnosis, classified as high risk, were significantly less likely to attend their genetics appointment (p = 0.010, p = 0.007, p = 0.005, respectively). Age, insurance type, distance from facility, and need for chemotherapy did not significantly impact consult completion rate. Of the patients who completed a genetic consult, 84.4% (n = 248) had genetic testing and 17.7% (n = 44) had a pathogenic variant. For patients who attended counseling, there were no significant factors that were predictive with receipt of genetic testing., Conclusions: In this study, there was a significant association between race and attending genetic counseling. Once counseled, most patients went on to receive genetic testing, and racial disparities in testing disappeared, emphasizing the value of providing additional education about the importance and purpose of genetic testing., (© 2024. The Author(s).)

Objectives: To identify predictors of referral and completion of germline genetic testing among newly diagnosed ovarian cancer patients, with a focus on geographic social deprivation, oncologist-level practices, and time between diagnosis and completion of testing., Methods: Clinical and sociodemographic data were abstracted from medical records of patients newly diagnosed with ovarian cancer between 2014 and 2019 in the University of North Carolina Health System. Factors associated with referral for genetic counseling, completion of germline testing, and time between diagnosis and test results were identified using multivariable regression., Results: 307/459 (67%) patients were referred for genetic counseling and 285/459 (62%) completed testing. The predicted probability of test completion was 0.83 (95% CI: 0.77-0.88) for patients with a referral compared to 0.27 (95% CI: 0.18-0.35) for patients without a referral. The predicted probability of referral was 0.75 (95% CI: 0.69-0.82) for patients at the 25th percentile of ZIP code-level Social Deprivation Index (SDI) and 0.67 (0.60-0.74) for patients at the 75th percentile of SDI. Referral varied by oncologist, with predicted probabilities ranging from 0.47 (95% CI: 0.32-0.62) to 0.93 (95% CI: 0.85-1.00) across oncologists. The median time between diagnosis and test results was 137 days (IQR: 55-248 days). This interval decreased by a predicted 24.46 days per year (95% CI: 37.75-11.16)., Conclusions: We report relatively high germline testing and a promising trend in time from diagnosis to results, with variation by oncologist and patient factors. Automated referral, remote genetic counseling and sample collection, reduced out-of-pocket costs, and educational interventions should be explored., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The American Society of Clinical Oncology recommends all patients with high-grade serous ovarian carcinoma (HGSC) undergo germline genetic testing. Genetic consultation rates in Ontario, Canada, only reached 13.3% in 2011. In 2016, PARP inhibitor maintenance therapy became available in Ontario for BRCA-positive HGSC patients. Given expanding treatment options, we re-examined genetic consultation rates among HGSC patients., Methods: This retrospective cohort study identified patients diagnosed with HGSC between 2012 and 2019 using population-based administrative data from Ontario. Genetics consultations were identified using Ontario Health Insurance Plan billing codes. Consultation rates over time were analyzed using Cochran-Armitage trend test and segmental regression analysis. Multivariable analysis identified factors associated with attending genetics consultation., Results: This study included 4645 HGSC patients. The mean age was 64.2 years (±SD 12.3); 56.3% had stage 3-4 disease. Overall, approximately 35% attended genetics consultations. The genetic consultation rate per year increased significantly from 21.6% to 42.6% (P < 0.001). Shorter times between diagnosis and genetics consult were observed after PARP inhibitors became available (68.1 vs 34.1 weeks, P < 0.001). Patients treated at designated cancer centers (odds ratio [OR] 2.11, P < 0.001), diagnosed in later years (OR 1.33, P < 0.001), and from higher income groups (P < 0.05) were more likely to attend genetics consultation; older patients were less likely (OR 0.98, P < 0.001). After PARP inhibitors became available, consultation rates plateaued (P < 0.001)., Conclusions: Between 2012 and 2019, genetic consultation rates improved significantly among HGSC patients; however, a large proportion of patients never attended consultation. Further exploration of barriers to care is warranted to improve consultation rates and ensure equitable access to care., (© 2024 International Federation of Gynecology and Obstetrics.)

Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year overall survival rate of 10%. In November 2018, NCCN recommended that all patients with PDAC receive genetic counseling (GC) and germline testing regardless of family history. We hypothesized that patients with PDAC were more likely to be referred for testing after this change to the guidelines, regardless of presumed predictive factors, and that compliance would be further improved following the implementation of a hereditary cancer clinic (HCC)., Methods: We conducted a single-institution retrospective analysis of patients diagnosed with PDAC from June 2017 through December 2021 at University of California, Irvine. We compared rates of genetics referral among patients in different diagnostic eras: the 18-month period before the NCCN Guideline change (pre-NCCN era: June 2017 through November 2018), 14 months following the change (post-NCCN era: December 2018 through January 2020), and 18 months after the creation of an HCC (HCC era: June 2020 through December 2021). Family and personal cancer history, genetics referral patterns, and results of GC were recorded. Data were compared using chi-square, Fisher exact, and multivariate analyses., Results: A total of 335 patients were treated for PDAC (123 pre-NCCN, 109 post-NCCN, and 103 HCC) at University of California, Irvine. Demographics across groups were comparable. Prior to the guideline changes, 30% were referred to GC compared with 54.7% in the post-NCCN era. After the implementation of the HCC, 77.4% were referred to GC (P<.0001). The odds ratio (OR) for referral to GC among patients with a positive family history of cancer progressively decreased following the change (pre-NCCN era: OR, 11.90 [95% CI, 3.00-80.14]; post-NCCN era: OR, 3.39 [95% CI, 1.13-10.76]; HCC era: OR, 3.11 [95% CI, 0.95-10.16])., Conclusions: The 2018 updates to the NCCN Guidelines for PDAC recommending germline testing for all patients with PDAC significantly increased GC referral rates at our academic medical center. Implementation of an HCC further boosted compliance with guidelines.

Genetic testing for cancer predisposition has been curtailed by the cost of sequencing, and testing has been restricted by eligibility criteria. As the cost of sequencing decreases, the question of expanding multi-gene cancer panels to a broader population arises. We evaluated how many additional actionable genetic variants are returned by unrestricted panel testing in the private sector compared to those which would be returned by adhering to current NHS eligibility criteria. We reviewed 152 patients referred for multi-gene cancer panels in the private sector between 2014 and 2016. Genetic counselling and disclosure of all results was standard of care provided by the Consultant. Every panel conducted was compared to current eligibility criteria. A germline pathogenic / likely pathogenic variant (P/LP), in a gene relevant to the personal or family history of cancer, was detected in 15 patients (detection rate of 10%). 46.7% of those found to have the P/LP variants (7 of 15), or 4.6% of the entire set (7 of 152), did not fulfil NHS eligibility criteria. 46.7% of P/LP variants in this study would have been missed by national testing guidelines, all of which were actionable. However, patients who do not fulfil eligibility criteria have a higher Variant of Uncertain Significance (VUS) burden. We demonstrated that the current England NHS threshold for genetic testing is missing pathogenic variants which would alter management in 4.6%, nearly 1 in 20 individuals. However, the clinical service burden that would ensue is a detection of VUS of 34%., (© 2022. The Author(s).)

The government-funded 'Punjab Thalassaemia Prevention Project' (PTPP) in Pakistan includes cascade screening for biological relatives of children with beta-Thalassaemia Major (β-TM). However, there is low uptake of cascade screening. This paper presents the (i) development of a paper-based 'decision support intervention for relatives' (DeSIRe) to enable PTPP Field Officers to facilitate informed decision making about carrier testing, and (ii) assessment of the feasibility and acceptability of the DeSIRe. The intervention was developed using the International Patient Decision Aids Standards quality criteria and Ottawa Decision Support Framework. Twelve focus groups were conducted (September and October 2020) to explore the views of healthcare professionals (HCPs) and relatives of children with β-TM, in six cities. The focus groups were attended by 117 participants (60 HCPs and 57 relatives). Thematic analysis showed that the DeSIRe was considered acceptable for supporting relatives to make informed decisions about cascade screening, and potentially feasible for use in clinical practice. Suggestions for changing some words, the structure and adding information about how carrier testing relates to consanguineous marriages will enable further development of the DeSIRe. Participants generally welcomed the DeSIRe; however, they highlighted the perceived need to use more directive language, hence showed a cultural preference for directive genetic counselling. The findings highlight challenges for researchers using western theories, frameworks, policies and clinical guidelines to develop decision support interventions for implementation more globally. Future research is needed to evaluate the use of the DeSIRe in routine practice and whether it enables relatives to make informed decisions., (© 2021. The Author(s).)

Introduction: Lobular carcinoma in situ (LCIS), atypical ductal and lobular hyperplasia (AH) increase breast cancer risk. We examined risk management recommendations (RMR) and acceptance in AH/LCIS., Methods: All patients with AH/LCIS on core needle biopsy from 2013 to 2016 at our institution were identified; cancer patients were excluded. Univariate and multivariate analysis examined factors associated with management., Results: 98 % of patients were evaluated by breast surgeons and 53 % underwent risk model calculation (RC). 77 % had new RMR. RMR of MRI screening (MRI), genetic counselling (GC) and medical oncology (MO) referral were 41 %, 18 %, 77 %, respectively. MRI screening was more likely recommended in those with strong family history (p = 0.01), and high RC (p < 0.001). Uptake of at least one RMR did not occur in 84 % of patients. Use of RC correlated with MO acceptance (p = 0.049)., Conclusions: Diagnosis of atypia has the potential to change risk management for most, however only 16 % of patients accepted all RMR., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Preconception and prenatal carrier screening is designed to provide reproductive risk information, but carriers for some autosomal recessive or X-linked conditions also have personal health risks. This study investigated the prevalence of and inclusion of personal health implications in pre- and post-test counseling., Methods: Twelve genetic conditions with personal health risks for carriers included on carrier screening panels but not otherwise screened routinely were identified (e.g., Gaucher disease with Parkinson's disease risk). A retrospective review was performed of patients with a positive carrier screen for one of these conditions at our center from 2012 to 2019., Results: Of 6147 individuals that had carrier screening for one of the twelve conditions, 96 (1.56%) did not report a known family history and screened positive for one of the conditions. Testing was ordered largely by reproductive endocrinologists (51.0%) and genetic counselors (35.4%). Most individuals did not receive pre- (96.8%) or post-test (64.6%) counseling about personal health risks. Post-test counseling was performed principally by genetic counselors (97.1%). For carriers of conditions with guidelines for specialist referral, most individuals (75.9%) were referred., Conclusion: Expanded genetic carrier screening increasingly identifies individuals with personal health implications, but patients are frequently not counseled before or after testing. These findings stress the importance of developing guidelines for practitioners about expanded carrier screening counseling and follow-up., (© 2021 John Wiley & Sons Ltd.)

Exome sequencing (ES) is an important diagnostic tool for individuals with neurodevelopmental disorders (NDD) and/or multiple congenital anomalies (MCA). However, the cost of ES limits the test's accessibility for many patients. We evaluated the yield of publicly funded clinical ES, performed at a tertiary center in Israel, over a 3-year period (2018-2020). Probands presented with (1) moderate-to-profound global developmental delay (GDD)/intellectual disability (ID); or (2) mild GDD/ID with epilepsy or congenital anomaly; and/or (3) MCA. Subjects with normal chromosomal microarray analysis who met inclusion criteria were included, totaling 280 consecutive cases. Trio ES (proband and parents) was the default option. In 252 cases (90.0%), indication of NDD was noted. Most probands were males (62.9%), and their mean age at ES submission was 9.3 years (range 1 month to 51 years). Molecular diagnosis was reached in 109 probands (38.9%), mainly due to de novo variants (91/109, 83.5%). Disease-causing variants were identified in 92 genes, 15 of which were implicated in more than a single case. Male sex, families with multiple-affected members and premature birth were significantly associated with lower ES yield (p < 0.05). Other factors, including MCA and coexistence of epilepsy, autism spectrum disorder, microcephaly or abnormal brain magnetic resonance imaging findings, were not associated with the yield. To conclude, our findings support the utility of clinical ES in a real-world setting, as part of a publicly funded genetic workup for individuals with GDD/ID and/or MCA., (© 2021. The Author(s).)

Background: Approximately 15% of colorectal cancers (CRCs) are deficient in DNA mismatch repair proteins (dMMR), a characteristic that can occur in both sporadic and hereditary CRC. Due to sparse studies on dMMR CRC in the Brazilian population, we conducted a retrospective analysis of referral rates for Genetic Cancer Risk Assessment of this population and also describing clinical and molecular characterization of these tumors., Methods: A retrospective, longitudinal, and unicenter study that included patients with dMMR CRC detected by IHC analysis from Pathology Database of our institution, from January 2015 to July 2017., Results: MMR IHC testing was performed in 998 CRC tumors, and 78 tumors (7.8%) had dMMR. The mean age at diagnosis was 56.8 years (17-90), and most patients were female (41 out of 78, 52.6%). Of the 52 patients with right-sided CRC, 40 tumors (77%) had loss of the MLH1 and/or PMS2 expression, and 12 tumors (23%) had loss of MSH2 and/or MSH6 expression (p = 0.005). From 78 patients with dMMR CRC, only 43 patients (55.1%) were referred for genetic counseling (GC), and of them, only 33 patients (76.7%) really went to GC consultation. A total of 21 patients with dMMR CRC performed genetic testing., Conclusion: Overall, genetic referral was less than expected in our population. Most of dMMR CRC patients did not receive GC, even in a cancer center, either due to the absence of referral or personal decision and few patients who pursued genetic counseling performed genetic testing., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Genetic counseling and germline testing have an increasingly important role for patients with prostate cancer (PCa); however, recent data suggests they are underutilized. Our objective was to perform a qualitative study of the barriers and facilitators of germline genetic evaluation among physicians who manage PCa., Methods: We conducted semi-structured interviews with medical oncologists, radiation oncologists, and urologists from different U.S. practice settings until thematic saturation was achieved at n = 14. The interview guide was based on the Tailored Implementation in Chronic Diseases Framework to identify key determinants of practice. Interview transcripts were independently coded by ≥2 investigators using a constant comparative method., Results: The decision to perform or refer for germline genetic evaluation is affected by factors at multiple levels. Although patient factors sometimes play a role, the dominant themes in the decision to conduct germline genetic evaluation were at the physician and organizational level. Physician knowledge, coordination of care, perceptions of the guidelines, and concerns about cost were most frequently discussed as the main factors affecting utilization of germline genetic evaluation., Conclusions: There are currently numerous barriers to implementation of germline genetic evaluation for PCa. Efforts to expand physician education, to develop tools to enhance genetics in practice, and to facilitate coordination of care surrounding genetic evaluation are important to promote guideline-concordant care., (© 2021 Wiley Periodicals LLC.)

Purpose: Several professional organizations recommend universal genetic assessment for people with ovarian cancer as identifying pathogenic variants can affect treatment, prognosis, and all-cause mortality for patients and relatives. We sought to evaluate the literature on genetic assessment for women with ovarian cancer and determine if any interventions or patient characteristics drive utilization of services., Methods: We searched key electronic databases to identify trials that evaluated genetic assessment for people with ovarian cancer. Trials with the primary aim to evaluate utilization of genetic assessment with or without interventions were included. Eligible trials were subjected to meta-analysis and the moderating influence of health interventions on rates of genetic assessment were examined., Results: A total of 35 studies were included (19 report on utilization of genetic services without an intervention, 7 with an intervention, and 9 with both scenarios). Without an intervention, pooled estimates for referral to genetic counseling and completion of genetic testing were 39% [CI 27-53%] and 30% [CI 19-44%]. Clinician-facilitated interventions included: mainstreaming of genetic services (99% [CI 86-100%]), telemedicine (75% [CI 43-93%]), clinic-embedded genetic counselor (76% [CI 32-95%]), reflex tumor somatic genetic assessment (64% [CI 17-94%]), universal testing (57% [28-82%]), and referral forms (26% [CI 10-53%]). Random-effects pooled proportions demonstrated that Black vs. White race was associated with a lower rate of genetic testing (26%[CI 17-38%] vs. 40% [CI 25-57%]) as was being un-insured vs. insured (23% [CI 18-28%] vs. 38% [CI 26-53%])., Conclusions: Reported rates of genetic testing for people with ovarian cancer remain well below the goal of universal testing. Interventions such as mainstreaming can improve testing uptake. Strategies aimed at improving utilization of genetic services should consider existing disparities in race and insurance status., Competing Interests: Declaration of Competing Interest Kevin Holcomb serves as a consultant for Johnson and Johnson and receives research support from Fujirebio Diagnostics, outside the submitted work. The other authors made no disclosures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Clinical diagnostic genome-wide (exome or genome) sequencing (GWS) in British Columbia requires funding approval by a provincial agency on a case-by-case basis. The CAUSES Clinic was a pediatric translational trio-based GWS study at BC Children's and Women's Hospitals. Referrals to the CAUSES Clinic were made through a Genomic Consultation Service (GCS), a multidisciplinary team led by genetic counsellors that provided advice regarding genomic testing for physicians considering GWS for their patients. Here we review the outcomes of the GCS, focusing on patients not recommended for the CAUSES Study., Methods: Demographic, clinical, and testing data were abstracted from patient charts. Logistic regression analysis was used to explore associations between demographic and clinical variables and two outcomes: the type of recommendation and referring physicians' decisions to follow the recommendation., Results: Of 972 GCS referrals, 248 patients were not referred to the CAUSES Study. GWS (vs. a targeted test; e.g. multi-gene panel) was more likely to be recommended to physicians of patients with ID than physicians of patients without ID (OR = 2.98; 95% CI = 1.46 to 6.27; n = 149). In total, 40% of physicians who were recommended to pursue clinical genomic testing submitted an application for funding approval; 71% of applications were approved for funding. Among approved tests, 50% resulted in a diagnosis, including 33% of targeted tests and 82% of GWS tests (χ 2 (1) = 5.0, p = 0.026)., Conclusion: The GCS provided an effective model in which physicians can interface with genetic specialists, including genetic counsellors, to facilitate appropriate genomic test selection., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Purpose: To examine the benefit of telehealth over current delivery options in oncology practices without genetic counselors., Methods: Participants meeting cancer genetic testing guidelines were recruited to this multi-center, randomized trial comparing uptake of genetic services with remote services (telephone or videoconference) to usual care in six predominantly community practices without genetic counselors. The primary outcome was the composite uptake of genetic counseling or testing. Secondary outcomes compare telephone versus videoconference services., Results: 147 participants enrolled and 119 were randomized. Eighty percent of participants in the telehealth arm had genetic services as compared to 16% in the usual care arm (OR 30.52, p < 0.001). Five genetic mutation carriers (6.7%) were identified in the telehealth arm, compared to none in the usual care arm. In secondary analyses, factors associated with uptake were lower anxiety (6.77 vs. 8.07, p = 0.04) and lower depression (3.38 vs. 5.06, p = 0.04) among those who had genetic services. There were no significant differences in change in cognitive or affective outcomes immediately post-counseling and at 6 and 12 months between telephone and videoconference arms., Conclusion: Telehealth increases uptake of genetic counseling and testing at oncology practices without genetic counselors and could significantly improve identification of genetic carriers and cancer prevention outcomes., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Changing practice guidelines and recommendations have important implications for cancer survivors. This study investigated genetic testing patterns and outcomes and reported family history of pancreatic cancer (FHPC) in a large registry population of breast cancer (BC) patients. Variables including clinical and demographic characteristics, FHPC in a first or second-degree relative, and genetic testing outcomes were analyzed for BC patients diagnosed between 2010 and 2018 in the NYU Langone Health Breast Cancer Database. Among 3334 BC patients, 232 (7%) had a positive FHPC. BC patients with FHPC were 1.68 times more likely to have undergone genetic testing (p < 0.001), but 33% had testing for BRCA1/2 only and 44% had no genetic testing. Pathogenic germline variants (PGV) were identified in 15/129 (11.6%) BC patients with FHPC, and in 145/1315 (11.0%) BC patients without FHPC. Across both groups, updates in genetic testing criteria and recommendations could impact up to 80% of this cohort. Within a contemporary cohort of BC patients, 7% had a positive FHPC. The majority of these patients (56%) had no genetic testing, or incomplete testing by current standards, suggesting under-diagnosis of PC risk. This study supports recommendations for survivorship care that incorporate ongoing genetic risk assessment and counseling.

Background: An important number of breast and ovarian cancer cases is due to a strong genetic predisposition. The main tool for identifying individuals at risk is recognizing a suggestive family history of cancer. We present a prospective study on applying three selected clinical guidelines to a cohort of 1000 Slovenian women to determine the prevalence of at-risk women according to each of the guidelines and analyze the differences amongst the guidelines., Methods: Personal and family history of cancer was collected for 1000 Slovenian women. Guidelines by three organizations: National Comprehensive Cancer Network (NCCN), American College of Medical Genetics in cooperation with National Society of Genetic Counselors (ACMG/NSGC), and Society of Gynecologic Oncology (SGO) were applied to the cohort. The number of women identified, the characteristics of the high-risk population, and the agreement between the guidelines were explored., Results: NCCN guidelines identify 13.2% of women, ACMG/NSGC guidelines identify 7.1% of women, and SGO guidelines identify 7.0% of women from the Slovenian population, while 6.2% of women are identified by all three guidelines as having high-risk for hereditary breast and ovarian cancer., Conclusions: We identified 13.7% of women from the Slovenian population as being at an increased risk for breast and ovarian cancer based on their personal and family history of cancer using all of the guidelines. There are important differences between the guidelines. NCCN guidelines are the most inclusive, identifying nearly twice the amount of women as high-risk for hereditary breast and ovarian cancer as compared to the AGMG/NSCG and SGO guidelines in the Slovenian population.

Objective: To assess the presence of clinically actionable results and other genetic findings in an otherwise healthy population of adults seen in a medical practice setting and offered "predictive" genomic testing., Patients and Methods: In 2014, a predictive genomics clinic for generally healthy adults was launched through the Mayo Clinic Executive Health Program. Self-identified interested patients met with a genomic nurse and genetic counselor for pretest advice and education. Two genome sequencing platforms and one gene panel-based health screen were offered. Posttest genetic counseling was available for patients who elected testing. From March 1, 2014, through June 1, 2019, 1281 patients were seen and 301 (23.5%) chose testing. Uptake rates increased to 36.3% [70 of 193]) in 2019 from 11.8% [2 of 17] in 2014. Clinically actionable results and genetic findings were analyzed using descriptive statistics., Results: Clinically actionable results were detected in 11.6% of patients (35 of 301), and of those, 51.7% (15 of 29) with a cancer or cardiovascular result = did not have a personal or family history concerning for a hereditary disorder. The most common actionable results were in the BCHE, BRCA2, CHEK2, LDLR, MUTYH, and MYH7 genes. A carrier of at least one recessive condition was found in 53.8% of patients (162 of 301). At least one variant associated with multifactorial disease was found in 44.5% (134 of 301) (eg, 25 patients were heterozygous for the F5 factor V Leiden variant associated with thrombophilia risk)., Conclusion: Our predictive screening revealed that 11.6% of individuals will test positive for a clinically actionable, likely pathogenic/pathogenic variant. This finding suggests that wider knowledge and adoption of predictive genomic services could be beneficial in medical practice, although additional studies are needed., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Introduction: The use of restricted versus expanded panel genetic testing in breast cancer is controversial, with some institutions offering predominantly abbreviated gene panel testing. Our community program has offered larger panel testing for several years. We sought to evaluate the outcomes of large panel genetic testing and understand their impact on patient care., Methods: A retrospective review of our multi-institutional tumor registry was performed from 2015 to 2018 for patients undergoing surgery for breast cancer. Referral to genetic counseling and outcomes of panel testing were examined., Results: 2237 patients met study criteria. Median age was 63 years (range 22-99). Eight hundred and thirty-eight patients (37.4%) were referred for genetic counseling. Of these patients, 509 (60.7%) had negative results, 108 (12.8%) had deleterious mutations (37 not included in abbreviated panels), and 221 (26.3%) had variants of undetermined significance (VUS). Bilateral mastectomy rates for patients with deleterious mutations were 53.7%, versus 31% for negative and 32.6% for VUS., Discussion: Large panel testing finds a significant number of actionable mutations. The increased identification of VUS did not result in higher mastectomy rates., Competing Interests: Declaration of competing interest None of the authors have conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Integration of genetic testing into routine oncology care could improve access to testing. This systematic review investigated interventions and the tailored implementation strategies aimed at increasing access to genetic counselling and testing and identifying hereditary cancer in oncology., Methods: The search strategy results were reported using the PRISMA statement and four electronic databases were searched. Eligible studies included routine genetic testing for breast and ovarian cancer or uptake after universal tumour screening for colorectal or endometrial cancer. The titles and abstracts were reviewed and the full text articles screened for eligibility. Data extraction was preformed using a designed template and study appraisal was assessed using an adapted Newcastle Ottawa Scale. Extracted data were mapped to Proctor's et al outcomes and the Consolidated Framework for Implementation Research and qualitatively synthesised., Results: Twenty-seven studies, published up to May 2020, met the inclusion criteria. Twenty-five studies ranged from poor (72%), fair to good (28%) quality. Most interventions identified were complex (multiple components) such as; patient or health professional education, interdisciplinary practice and a documentation or system change. Forty-eight percent of studies with complex interventions demonstrated on average a 35% increase in access to genetic counselling and a 15% increase in testing completion. Mapping of study outcomes showed that 70% and 32% of the studies aligned with either the service and client or the implementation level outcome and 96% to the process or inner setting domains of the Consolidated Framework for Implementation Research., Conclusion: Existing evidence suggests that complex interventions have a potentially positive effect towards genetic counselling and testing completion rates in oncology services. Studies of sound methodological quality that explore a greater breadth of pre and post implementation outcomes and informed by theory are needed. Such research could inform future service delivery models for the integration of genetics into oncology services., Competing Interests: The authors declare that they have no competing interests.

The demand for genetic testing of hereditary breast cancer genes such as BRCA1 and BRCA2 has continued to increase with the lowering costs of testing, raised awareness in the general public, and implications for breast cancer treatment when a patient is identified as having a germline pathogenic variant. Historically within Australia, patients affected by high genetic risk breast cancers have been referred to a familial cancer centre (FCC) for assessment and testing, resulting in wait times for an appointment for pre- and post-test genetic counselling and an increased demand on the public-funded FCC. To improve patient access and pace of genetic testing, as well as refocus FCC resources, a mainstream clinical genetic testing program was rolled out in September 2017 through the Parkville FCC (PFCC) in Australia at 10 hospital sites. This program enables specialist doctors of eligible patients affected by breast cancer to arrange genetic testing directly at an oncology/surgical appointment and follow up the results as part of the patients' routine clinical care. In this model, the specialist doctor is responsible for any treatment implications of the genetic test result, and the PFCC is responsible for result interpretation, future cancer risk, family cascade testing and segregation testing where warranted. To date the program has had successful uptake, a notable pathogenic variant detection rate, reduced the burden on the PFCC enabling a reallocation of resources and has streamlined the process of genetic testing for eligible patients. Investigation into the patient and clinician experiences of the mainstream program is required.

Aim:  FLABRA evaluated the prevalence of BRCA mutations, genetic counseling and management approaches in patients with ovarian cancer in Latin America. Patients & methods: Patients with ovarian cancer from six Latin-American countries were enrolled. Tumor samples were tested for BRCA mutations ( BRCA mut ). In cases with BRCA mut , blood samples were analyzed to determine germline versus somatic mutations. Medical records were reviewed for counseling approach and treatment plan. Results: From 472 patients enrolled, 406 samples yielded conclusive results: 282 were BRCA wild-type ( BRCA wt ), 115 were  BRCA mut  and nine were variants of uncertain significance. In total, 110/115 were tested for germline mutations (77 germline and 33 somatic). Conclusion: Tumor testing to identify mutations in BRCA1/2  in ovarian cancer can help optimize treatment choices, meaning fewer patients require germline testing and genetic counseling, a scant resource in Latin America. Clinical trial registration: NCT02984423 (ClinicalTrials.gov).

Predictive BRCA testing is offered to asymptomatic individuals to predict future risk where a variant has been identified in a relative. It is uncertain whether all eligible relatives access testing, and whether this is related to health care inequalities. Our aim was to analyse trends and inequalities in uptake of testing, and identify predictors of testing and time-to-receipt of testing. A database from April 2010 to March 2017 was collated. Multivariate analysis explored individual associations with testing. Predictor variables included gender, BRCA test type, cancer history, Index of Multiple Deprivation (IMD) and education status. To evaluate factors associated with time-to-testing, a Cox proportional-hazards (CP) model was used. Of 779 tests undertaken, 336 (43.1%) were identified with a BRCA variant. A total of 537 (68.9%) were female and in 83.4% (387/464) of probands, predictive testing was received by relatives. Analysis identified inequalities since decreased testing was found when the proband was unaffected by cancer (OR 0.14, 95% CI 0.06-0.33). Median time-to-testing was 390 days (range, 0-7090 days) and the CP model also identified inequalities in the hazard ratio (HR) for testing for people aged >40 was higher than for aged <40 (HR 1.41, 95% CI 1.20-1.67) and BRCA2 testing was higher than for BRCA1 testing (HR 1.39, 95% CI 1.18-1.64). Reduced testing was found when probands were unaffected by cancer and time-to-testing was found to vary by age and BRCA1/2 test. Given limited study sample size, further research is recommended to examine inequalities in predictive BRCA testing.

Background: Ongoing clinical trials are investigating PARP inhibitors to target the DNA damage repair (DDR) pathway in prostate cancer. DDR mutation screening will guide treatment strategy and assess eligibility for clinical trials. Materials & methods: This systematic review estimated the rate of DDR mutation testing or genetic counseling among men with or at risk of prostate cancer. Results: From 6856 records, one study fulfilled the inclusion criteria and described men undiagnosed with prostate cancer with a family history of BRCA1/2 mutation who received DDR mutation testing. Conclusion: With only one study included in this first systematic review of DDR mutation testing or genetic counseling in men with or at risk of prostate cancer, more research is warranted.

Background: Chromosomal-microarray-analysis (CMA) can identify variants of uncertain clinical significance, susceptibility-loci for neurodevelopmental conditions, and risk for adult-onset conditions. We explored choices made by couples undergoing prenatal CMA, their understanding of these findings, reasons for and against receiving them, and whether they believe parents or professionals should decide which are disclosed., Methods: Semi-structured interviews were conducted with women (n = 27) or their partners (n = 15) during the week following prenatal CMA testing and analyzed using grounded theory., Results: Over half the interviewees (55%) recalled at least two of the three types of CMA results they chose whether to receive. Sixty-four percent found the choice simple, whereas 36% found it difficult. All participants could clearly explain their choices, which were based on the perceived actionability and psychological impact of the information. Sixty percent viewed their choice favorably, whereas ~21% would have preferred clinicians to decide for them. More women than men, and more decisive than indecisive participants supported parental choice., Conclusion: Overall, expectant parents can make informed choices about which uncertain findings about their fetuses they wish to receive, and value the opportunity to tailor results to their values and wishes. Arguments presented provide the basis for a decision-aid tool for expecting parents., (© 2020 John Wiley & Sons Ltd.)

Background: Emerging data suggest screening mammography may be effective in detecting breast cancer early in high-risk men. We evaluated current screening recommendations as a risk management strategy in men at elevated risk for breast cancer., Patients and Methods: This institutional review board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant study reviewed consecutive men who underwent genetic counseling and multigene panel testing (MGPT) for breast cancer risk assessment at our institution between 2012 and 2018. Patient risk factors, test indications, and MGPT outcomes were recorded, then correlated with screening recommendations by either clinical breast examination or screening mammography. Recommendation consistency among practitioners was evaluated. Patient adherence to screening mammography (defined as undergoing screening mammography as recommended) was assessed. Statistical analysis was performed at the 2-sided 5% significance level., Results: A total of 414 asymptomatic men underwent both genetic counseling and MGPT (mean age, 47 years; range, 18-91 years) for breast cancer risk assessment. Of this group, 18 (4.3%) of 414 had a personal history of breast cancer, and 159 (38.4%) of 414 had a family history of breast cancer before MGPT. Among 112 men with positive MGPT results, BRCA1/2 mutations were the most common (56.3%, 63/112). Most BRCA mutation carriers (80.9%, 51/63) were recommended clinical breast examination only. Only 5.9% (2/34) BRCA2 and 10.3% (3/29) BRCA1 carriers were recommended screening mammograms (7.9%, 5/63 of all BRCA carriers). Among men with a personal history of breast cancer, only 9 (50%) of 18 were recommended screening mammograms. Overall adherence to screening mammogram in men was 71.4% (10/14), which ultimately yielded two cancers. Breast cancer screening recommendations varied widely among practitioners, with some recommending clinical breast examination only, and others also recommending mammography., Conclusion: Men who are found to be at an elevated risk for breast cancer after undergoing genetic counseling and testing currently receive relatively inconsistent screening recommendations., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Germline genetic testing is crucial to the care of ovarian cancer patients, and as part of the guideline-based care for ovarian cancer patient's adherence to this recommendation has been low. We sought to determine whether embedding a genetic counselor (GC) within a medical and gynecologic oncology clinic would increase testing rates and improve the timeliness of testing., Methods: Prospective cohort study of 358 ovarian cancer patients seen by medical and gynecologic oncologists between 2013 and 2015. Rates of referrals, completion of counseling, and genetic testing and timeliness of counseling were abstracted before and after a GC was embedded in the clinic in 2014. An additional year of data (2015) was collected to evaluate sustainability of the intervention., Results: Between 2013 and 2015, 88-92% of women were referred for genetic testing, but in 2013 only 66% completed counseling and 61% were tested. After a GC was embedded in the clinic in 2014, more than 80% of referred women completed counseling and germline genetic testing. Time to genetic counseling also decreased from a median of 107 to 40 days, irrespective of age and cancer family history (p < 0.01)., Conclusions: Embedding a GC into the workflow for ovarian cancer patients is an effective way of improving access to genetic counseling, testing rates, and the timeliness of testing., Competing Interests: Declaration of Competing Interest Dr. Judy E. Garber has the following COI: personal fees from Helix Genetics, Novartis Oncology, GTx, Aleta BioTherepeutics, H3 Biomedicine, Inc., Kronos Bio, American Society of Clinical Oncology (ASCO), James P. Wilmot Foundation, Inc., Diane Helis Henry Medical Research Foundation, and Adrienne Helis Melvin Medical Research Foundation, and other from Myriad Genetics, Astrazeneca, Ambry Genetics, Invitae Genetics, GV20 Therapeutics, American Association for Cancer Research, Breast Cancer Research Foundation, Konica Minolta, and Facing Our Risk of Cancer Empowered, outside the submitted work. Dr. Ursula Matulonis has the following COI: personal fees from Astrazeneca, Myriad Genetics, Clovis, Merck, Eli Lilly, Mersana, Geneos, Fuji Film, Cerulean, Immunogen, Novartis, and 2× Oncology, outside the submitted work. Ms. Kipnis reports personal fees from Invitae outside the submitted work. All other authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

There is an increased pressure to return results from research studies. In Iceland, deCODE Genetics has emphasised the importance of returning results to research participants, particularly the founder pathogenic BRCA2 variant; NM&#95;000059.3:c.771&#95;775del. To do so, they opened the website www.arfgerd.is . Individuals who received positive results via the website were offered genetic counselling (GC) at Landspitali in Reykjavik. At the end of May 2019, over 46.000 (19% of adults of Icelandic origin) had registered at the website and 352 (0.77%) received text message informing them about their positive results. Of those, 195 (55%) contacted the GC unit. Additionally, 129 relatives asked for GC and confirmatory testing, a total of 324 individuals. Various information such as gender and age, prior knowledge of the variant and perceived emotional impact, was collected. Of the BRCA2 positive individuals from the website, 74 (38%) had prior knowledge of the pathogenic variant (PV) in the family. The majority initially stated worries, anxiety or other negative emotion but later in the process many communicated gratitude for the knowledge gained. Males represented 41% of counsellees as opposed to less than 30% in the regular hereditary breast and ovarian (HBOC) clinic. It appears that counselling in clinical settings was more reassuring for worried counsellees. In this article, we describe one-year experience of the GC service to those who received positive results via the website. This experience offers a unique opportunity to study the public response of a successful method of the return of genetic results from research.

Purpose: The coronavirus disease (COVID-19) pandemic has had a profound impact on cancer care in the US Guidelines focused on the management of COVID-19, rather than healthcare needs of breast cancer patients requiring access to crucial services. This US survey of breast cancer survivors characterizes treatment delays early period in the pandemic., Methods: We developed a survey and administered it to 609 adult breast cancer survivors in the US. We used snowball sampling with invitations distributed via social media. We used logistic regression to select a model of delay from a pool of independent variables including race, cancer stage, site of care, health insurance, and age. We used descriptive statistics to characterize delay types., Results: Forty-four percent of participants reported cancer care treatment delays during the pandemic. Delays in all aspects of cancer care and treatment were reported. The only variable which had a significant effect was age (97 (.95, 99), p < 0.001) with younger respondents (M = 45.94, SD = 10.31) reporting a higher incidence of delays than older respondents (M = 48.98, SD = 11.10). There was no significant effect for race, insurance, site of care, or cancer stage., Conclusions: Our findings reveal a pervasive impact of COVID-19 on breast cancer care and a gap in disaster preparedness that leaves cancer survivors at risk for poor outcomes. Delays are critical to capture and characterize to help cancer providers and healthcare systems develop effective and patient-tailored processes and strategies to manage cases during the current pandemic wave, subsequent waves, and future disasters.

Background: The objective of the current study was to provide insight into the effect of coronavirus disease 2019 (COVID-19) on breast cancer screening, breast surgery, and genetics consultations., Methods: User data from a risk assessment company were collected from February 2 to April 11, 2020. The use of risk assessment was used as a proxy for the use of 3 breast cancer services, namely, breast imaging, breast surgery, and genetics consultation. Changes in the use of these services during the study period were analyzed., Results: All 3 services experienced significant declines after the COVID-19 outbreak. The decline in breast surgery began during the week of March 8, followed by breast imaging and genetics consultation (both of which began during the week of March 15). Breast imaging experienced the most significant reduction, with an average weekly decline of 61.7% and a maximum decline of 94.6%. Breast surgery demonstrated an average weekly decline of 20.5%. When surgical consultation was stratified as breast cancer versus no breast cancer, the decrease among in non-breast cancer patients was more significant than that of patients with breast cancer (a decline of 66.8% vs 11.5% from the pre-COVID average weekly volume for non-breast cancer patients and patients with breast cancer, respectively). During the week of April 5, use of genetics consultations dropped to 39.9% of the average weekly volumes before COVID-19., Conclusions: COVID-19 has had a significant impact on the number of patients undergoing breast cancer prevention, screening, diagnosis, and treatment., (© 2020 American Cancer Society.)

Objective: Referral to Genetics for pre-testing counseling may be inefficient for women with ovarian cancer. This study assesses feasibility of gynecologic oncologists directly offering genetic testing., Methods: A prospective pilot study was conducted at two gynecologic oncology hubs in an integrated healthcare system from May 1 to November 6, 2019. Gynecologic oncologists offered multigene panel testing to women with newly diagnosed ovarian cancer, followed by selective genetic counseling. Outcomes were compared between study participants and women from other hubs in the health system., Results: Of ovarian cancer patients at study sites, 40 participated and all underwent genetic testing. Of 101 patients diagnosed at other sites, 85% were referred to genetics (p = .0061 compared to pilot participants) and 67% completed testing (p < .0001). The time from diagnosis to blood draw and notification of result was 18.5 and 34 days for the pilot group compared to 25.5 and 53 days at other sites. Panel testing detected 9 (22.5%) and 7 (10.3%, p = .08) pathogenic mutations in each group, respectively. Patients and providers were highly satisfied with the streamlined process., Conclusion: Genetic testing performed at the gynecologic oncology point of care for patients with ovarian cancer is feasible, increases uptake of testing, and improves time to results., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To report the frequency of Lynch syndrome (LS) in a cohort of patients from Southeast Brazil bearing endometrial cancer (EC), using a tumor screening universal approach., Methods: A total of 242 endometrial carcinomas were screened by immunohistochemistry (IHC) and microsatellite instability (MSI) for detection of DNA mismatch repair deficiency (dMMR). MLH1 methylation was assessed to identify sporadic cases. Patients with dMMR tumors were recruited for germline variant analysis by next-generation sequencing of the MLH1, MSH2, MSH6, PMS2, and EPCAM genes., Results: Ninety-three out of 242 tumors (38.5%) were classified as dMMR based on MSI and IHC results. Of these, 54 cases were selected for germline analysis, and 37/54 (68.5%) were available for sequencing. Ten patients (10/37, 27%) harbored germline pathogenic or likely pathogenic variants, most of them in the MSH6 gene (4/10, 40%). Seven variants of uncertain significance were found. Eight novel germline variants were identified. The LS prevalence in our cohort was of at least 4.1%. LS patients presented lower mean age at cancer diagnosis compared with patients diagnosed with sporadic EC. Individuals with dMMR tumors, without germline pathogenic variants detected in LS-genes ("Lynch-like" syndrome), had an intermediate mean age at cancer diagnosis between LS and sporadic cases., Conclusion: This is the first report of the LS prevalence in EC screened by a universal approach in Brazil. Our findings contribute to a better understanding of the mutational landscape of this syndrome in Brazil, which is relevant for improved identification, genetic counseling, prevention and control of cancer in LS., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest regarding the research, authorship, and/or publication of this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Over the last decade, genetic testing (GT) had markedly spread in European countries and struggled the debate concerning the psychological effects on the population. The aim of this study was to investigate the individual tendencies of GT consumers in a sample of Italian citizens., Methods: A total of 152 Italian clients from GenomaLab, a private genetic company, were enrolled from February 2016 to September 2018 and completed an ad hoc survey., Results: Results showed that GT consumers were motivated to preserve their well-being, they felt responsible for their health, they were neither pessimistic nor optimistic toward negative occurrences, and poorly inclined to take high risks in their lives. Participants who had suffered from a disease in the past appear to be less tolerant to the uncertainty for future negative events., Conclusion: Our results depict Italian GT consumers as health-oriented, focused on prevention, who do not have a pessimistic perception of their condition but do not like to "bet" on their health, and probably their intention (and belief) is to acquire genetic information in order to reduce uncertainty and increase their decision-making "power" related to their health. Taken together, all these results contribute to describe the population of GT users in European countries, to regulate the provision of GT results and to entail the communication of genetic risk information based on a consumers' personal profile., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Background and Objectives: Many newly diagnosed breast cancer patients do not receive genetic counseling and testing at the time of diagnosis. We examined predictors of genetic testing (GT) in this population., Methods: Within a randomized controlled trial of proactive rapid genetic counseling and testing vs usual care, patients completed a baseline survey within 6 weeks of breast cancer diagnosis but before a definitive survey. We conducted a multinomial logistic regression to identify predictors of GT timing/uptake., Results: Having discussed GT with a surgeon was a dominant predictor (χ 2 (2, N = 320) = 70.13; P < .0001). Among those who discussed GT with a surgeon, patients who had made a final surgery decision were less likely to receive GT before surgery compared with postsurgically (OR [odds ratio] = 0.24; 95% confidence interval [CI] = 0.12-0.49) or no testing (OR = 0.28; 95% CI = 0.14-0.56). Older patients (OR = 0.95; 95% CI = 0.91-0.99) and participants enrolled in New York/New Jersey (OR = 0.22; 95% CI = 0.07-0.72) were less likely to be tested compared with receiving results before surgery. Those with higher perceived risk (OR = 1.02; 95% CI = 1.00-1.03) were more likely to receive results before surgery than to not be tested., Conclusions: This study highlights the role of patient-physician communication about GT as well as patient-level factors that predict presurgical GT., (© 2020 Wiley Periodicals, Inc.)

Background: Health information technology (IT) is becoming increasingly utilized by cancer genetic counselors (CGCs). We sought to understand the current engagement, satisfaction, and opportunities to adopt new health IT tools among CGCs., Methods: We conducted a mixed-mode survey among 128 board-certified CGCs using both closed- and open-ended questions. We then evaluated the utilization and satisfaction among 10 types of health IT tools, including the following: cancer screening tool, family health history (FHx) collection tools, electronic health records (EHRs), telegenetics software, pedigree drawing software, genetic risk assessment tools, gene test panel ordering tools, electronic patient education tools, patient communication tools, and family communication tools., Results: Seven of 10 health IT tools were used by a minority of CGCs. The vast majority of respondents reported using EHRs (95.2%) and genetic risk assessment tools (88.6%). Genetic test panel ordering software had the highest satisfaction rate (very satisfied and satisfied) at 80.0%, followed by genetic risk assessment tools (77.1%). EHRs had the highest dissatisfaction rate among CGCs at 18.3%. Dissatisfaction with a health IT tool was associated with desire to change: EHRs (p < .001), cancer screening tools (p = .010), genetic risk assessment tools (p = .024), and family history collection tools (p = .026). We found that nearly half of CGCs were considering adopting or changing their FHx tool (49.2%), cancer screening tool (44.9%), and pedigree drawing tool (41.8%)., Conclusion: Overall, CGCs reported high levels of satisfaction among commonly used health IT tools. Tools that enable the collection of FHx, cancer screening tools, and pedigree drawing software represent the greatest opportunities for research and development., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Purpose: Genetic counseling (GC) provides critical risk prediction information to women at-risk of carrying a genetic alternation; yet racial/ethnic and socioeconomic disparities persist with regard to GC uptake. This study examined patterns of GC uptake after a referral in a racially diverse population. Materials and Methods: In an urban academic medical center, medical records were reviewed between January 2016 and December 2017 for women who were referred to a genetic counselor for hereditary breast and ovarian cancer. Study outcomes were making an appointment (yes/no) and keeping an appointment. We assessed sociodemographic factors and clinical factors. Associations between factors and the outcomes were analyzed using chi square, and logistic regression was used for multivariable analysis. Results: A total of 510 women were referred to GC and most made appointments. More than half were white (55.3%) and employed (53.1%). No significant associations were observed between sociodemographic factors and making an appointment. A total of 425 women made an appointment and 268 kept their appointment. Insurance status ( p  = 0.003), marital status ( p  = 0.000), and work status ( p  = 0.039) were associated with receiving GC. In the logistic model, being married (odds ratio [OR] 2.119 [95% confidence interval, CI 1.341-3.347] p  = 0.001) and having insurance (OR 2.203 [95% CI 1.208-4.016] p  = 0.021) increased the likelihood of receiving counseling. Conclusions: Racial disparities in GC uptake were not observed in this sample. Unmarried women may need additional support to obtain GC. Financial assistance or other options need to be discussed during navigation as a way to lessen the disparity between women with insurance and those without.

Introduction: Preimplantation genetic testing (PGT) is growing in importance and volume internationally. International societies such as the European Society for Human Reproduction and Embryology compile international results and these data are published in scientific journals. We present the first compilation of practices, quality measuress and outcome data from Nordic clinics performing PGT., Material and Methods: We conducted a structured online survey of PGT practices in the Nordic countries to compare clinical and laboratory techniques, outcomes and quality measures applied in Nordic clinics. The survey was designed by the authors and answered by the authors and members of the study group. The outcome data represents results from 2018. Results and details were clarified through iteration with responding clinics while maintaining anonymity. Response rate in the study was 80%, with 8 of 10 clinics performing PGT responding., Results: Most of the PGT cycles in the Nordic countries are funded through the public healthcare system with University Hospitals performing the majority of treatments, 716/848, or 84.4%, of oocyte retrievals in this dataset. The genetic analyses are in five cases performed by the affiliated local genetic laboratory, and the remaining three consult with large international private enterprise laboratories. Genetic counseling is widely used. Results in the Nordic clinics compare well with international data. Systematic quality control procedures are in place and the larger clinics and laboratories utilize ISO certification or accreditation in the quality management. Automatic witnessing with detailed electronic documentation of laboratory processes is not utilized in the responding clinics, although a majority uses manual witnessing procedures in the laboratory. The outcome after PGT in terms of clinical pregnancy per transfer is around 40% per embryo transfer and compares well with international data., Conclusions: Preimplantation genetic testing is organized in rather few clinics in the Nordic countries and most of them use local laboratories for genetic analyses of the biopsies. Laboratory procedures are largely in accordance with international guidelines and the outcome after PGT in terms of clinical pregnancy per transfer is comparable to results in international reports., (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To describe uptake of carrier screening by male reproductive partners of prenatal and preconception patients., Methods: A retrospective database review of all prenatal and preconception patients seen for genetic counseling in Maternal Fetal Medicine clinics was performed. Descriptive statistics and chi-square analysis were used on the data set., Results: Within the study period, 6087 patients were seen for genetic counseling, of whom 661 were identified as a carrier of an autosomal recessive disorder by their referring provider or genetic counselor. Despite guidelines recommending partner testing for risk clarification when a woman is known to be a carrier of an autosomal recessive condition, only 41.5% male partners elected carrier screening to clarify the couple's reproductive risk, with a majority of males (75%) having screening consecutively. Of all assessed variables, the only significant predictors of male carrier screening uptake were female parity and earlier gestational age (p < .0001, and p = .001, respectively)., Conclusion: With less than half of male partners pursuing carrier screening when indicated, its utility becomes severely diminished. More research is needed to explore reasons why males elect or decline carrier screening., (© 2019 John Wiley & Sons, Ltd.)

Introduction : Carrier screening for recessive disorders is undertaken by prospective parents to inform their reproductive decisions. With the growing availability of affordable and comprehensive expanded carrier screening (ECS), it is expected that carrier screening will become a standard practice in the future. However, the impact of positive carrier screening results on the reproductive decisions of at-risk couples (ARCs) remains underexplored. Areas covered : We performed a systematic literature review to identify peer-reviewed publications describing the reproductive decisions of ARCs. Our search identified 19 relevant publications spanning the period 1994-2018. By synthesizing available evidence, we found that most ARCs chose to prevent the birth of an affected child and the decision to utilize preventive reproductive options was strongly influenced by the clinical nature of a disorder. However, there was also some heterogeneity in reproductive decisions within the same recessive disorders, suggesting that choices of ARCs can be influenced by factors other than the clinical nature of a disorder. Expert opinion : ECS is becoming increasingly common, which will result in the routine identification of many ARCs. Reproductive decision-making by ARCs is a complex and emotionally challenging process, highlighting the critical role of genetic counseling in the care for these potentially vulnerable patients.

Understanding the overall utility of biological testing for autism spectrum disorder (ASD) is essential for the development and integration of biomarkers into routine care. One measure related to the overall utility of biological testing is the knowledge that a person has about the condition he/she suffers from. However, a major gap towards understanding the role of knowledge in overall utility is the absence of studies that have assessed knowledge of autism along with its predictors within a representative sample of families within the context of routine care. The objective of this study was to measure knowledge of ASD among families within the routine care pathway for biological testing in ASD by examining the association between knowledge with potential correlates of knowledge namely sociodemographic factors, parental stress and distress, and time since diagnosis among parents whose child with ASD is undergoing clinical genetic testing. Parents of a child diagnosed with ASD (n = 85, Mage = 39.0, SD = 7.7) participating in an ongoing prospective genomics study completed the ASD Quiz prior to undergoing genetic testing for clinical and research purposes. Parents also completed self-reported measures of stress and distress. Parent stress and distress was each independently correlated with knowledge of ASD, rs ≥ 0.26, ps < 0.05. Stepwise regression analysis revealed a significant model accounting for 7.8% of the variance in knowledge, F (1, 82) = 8.02, p = 0.006. The only factor significantly associated with knowledge was parental distress, β = 0.30, p = 0.006. Parental stress, time since diagnosis, and sociodemographic factors were not significant predictors in this model. We concluded that families require tailored support prior to undergoing genetic testing to address either knowledge gaps or high distress. Ongoing appraisal of the testing process among families of diverse backgrounds is essential in offering optimal care for families undergoing genetic testing., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Approximately 60% of congenital pediatric hearing loss is of genetic etiology. To evaluate non-syndromic sensorineural hearing loss (NSSNHL), guidelines emphasize the use of comprehensive genetic testing (CGT) with next generation sequencing (NGS), yet these tests have limited accessibility, and potential CGT results may not be well understood. Thus, our objective was to analyze genetic testing practices and results for pediatric patients with NSSNHL., Methods: This was a retrospective chart review of pediatric patients (<18 years) diagnosed with NSSNHL from 2014 to 2017 at a tertiary pediatric hospital. Demographics, clinical data, CGT results, genetic testing practices and referral patterns were recorded and descriptively analyzed. Logistic regression models identified patient characteristics associated with pathogenic variants (PV) and variants of unknown significance (VOUS)., Results: 430 patients with congenital NSSNHL were included in the study. Genetic testing was ordered for 28% (n = 122) and resulted for 16% (n = 68). Most of the ordered tests (89%, n = 109) were the CGT panel. A majority (62%, n = 97) of the time in which genetic testing was not ordered, a referral for genetics consultation was placed. Amongst those with CGT results, a definitive genetic etiology was identified in 25% (n = 13), with less than half due to variants of GJB2/6. At least one PV was identified for 33% (n = 18), while at least one VOUS for 93% (n = 51). There were no significant differences in PV presence or number of VOUS across any characteristic except race. When compared to Caucasians, African Americans had significantly higher rates of VOUS with a rate ratio and 95% CI of 1.61 [1.11-2.34], p = 0.01, and Asians trended towards higher rates (1.96 [0.95-4.05], p = 0.06)., Conclusions: CGT is of high utility in the identification of relevant genetic variants and definitive genetic etiologies for pediatric patients with NSSNHL. Though guidelines recommend the early use of CGT, there are many barriers to appropriate testing and counseling, leading to low rates of CGT use at this single institution., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Genetic counseling in at-risk families is known to improve cancer prevention. Our study aimed to determine the rate of uptake of genetic counseling among adult children of BRCA1/2 mutation carriers and to identify the potential psychosocial factors associated with uptake of genetic counseling., Methods: A self-reported questionnaire was mailed to 328 BRCA1/2 mutation carriers 10 years after BRCA1/2 test disclosure. Of the 233 carriers who returned the questionnaire (response rate = 71%), 135 reported having children over age 18 years and were therefore included in the analysis. Generalized estimating equations models were used to identify the factors associated with uptake of genetic counseling among adult children of mutation carriers., Results: Data were gathered for a total of 296 children (46% male, 54% female). The vast majority were informed about the familial mutation (90.9%) and 113 (38%; 95% CI, 32%-44%) underwent genetic counseling. This percentage exceeded 80% in women over 40 years. In the multivariate model, female sex, advanced age, mutation in the father, diagnosis of cancer in the mutation-carrying parent after genetic testing, and good family relationships were all factors associated with higher uptake of genetic counseling., Conclusions: Adult children of BRCA1/2 mutation carriers in France do not undergo genetic counseling sufficiently often. Further studies should be conducted on the psychosocial factors that hinder the uptake of genetic counseling among adult children of BRCA1/2 mutation carriers., (© 2019 John Wiley & Sons, Ltd.)

The hereditary contribution to ovarian cancer has been increasingly recognized over the past decade, with a 2014 Society of Gynecologic Oncology (SGO) recommendation for all women with epithelial ovarian cancer to be considered for genetic testing. The objective of the study was to determine if disparities exist in genetic referrals and characterize referral patterns over time. A retrospective cohort study included all women diagnosed with invasive epithelial ovarian cancer at the University of Virginia from 2004 to 2015. Clinicopathologic data were abstracted from the electronic medical record and analyzed for association with genetic referral and testing. We identified 696 cases, with a median age of 62 years and a median follow up of 25.2 months (range 1-115). Thirty-four percent were referred for genetic counseling with an 80% genetic testing rate in those women. Referrals increased from a rate of 8% in 2004 to 68% in 2015. On multivariable analysis, papillary serous histology (OR 1.6, 95% CI 1.0-2.6), stage III disease (OR 3.4, 95% CI 1.6-7.5), ovarian cancer family history (OR 2.6, 95% CI 1.5-4.6), breast cancer family history (OR 1.7, 95% CI 1.1-2.5), and diagnosis after 2014 (OR 2.3, 95% CI 1.3-4.1) remained significantly associated with genetics referral. Older age and living > 100 miles away were associated with decreased referral (OR 0.97, 95% CI 0.95-0.99 per year and OR 0.49, 95% CI 0.28-0.86). As only 68% of women with epithelial ovarian cancer were referred in 2015 innovative strategies such as Medicare coverage for counseling are still needed to universalize testing.

Genetic counseling is under-utilized in women who meet family history criteria for BRCA1 and BRCA2 (BRCA1/2) testing, particularly among racial/ethnic minorities. We evaluated the uptake of BRCA1/2 genetic testing among women presenting for screening mammography in a predominantly Hispanic, low-income population of Washington Heights in New York City. We administered the Six-Point Scale (SPS) to women presenting for screening mammography at Columbia University Irving Medical Center (CUIMC) in the Washington Heights neighborhood of New York, NY. The SPS is a family history screener to determine eligibility for BRCA1/2 genetic testing based upon U.S. Preventive Services Task Force (USPSTF) guidelines that has been validated in low-income, multiethnic populations. Among women who underwent screening mammography at CUIMC between November 2014 and June 2016, 3,055 completed the SPS family history screener. Participants were predominantly Hispanic (76.7%), and 12% met family history criteria for BRCA1/2 testing, of whom <5% had previously undergone testing. In a multiethnic population, a significant proportion met family history criteria for BRCA1/2 testing, but uptake of genetic testing was low. Such underutilization of BRCA1/2 genetic testing among minorities further underscores the need to develop programs to engage high-risk women from underrepresented populations in genetic testing services., (Copyright © 2019. Published by Elsevier Inc.)

Background/objective: Despite increases in BRCA mutation testing, racial/ethnic disparities in counseling and testing have persisted for decades. The purpose of the review was to summarize recent literature as it relates to detecting, understanding, and reducing disparities in BRCA counseling and testing., Design: This is a narrative review of articles published January 2012 to July 2017 relevant to genetic testing and counseling, breast and ovarian cancer, and minority health and heath disparities. Twenty-three articles were included in this review., Results: Studies report lower counseling and/or testing rates for eligible racial/ethnic minorities among family members of high-risk individuals as well as among breast cancer survivors. Key barriers and facilitators of disparate BRCA counseling/testing that emerged in this review included awareness, cost-related factors, stress and distrust, family concerns and communication, and provider communication and referral. To address differential access to and use of BRCA testing services and expand testing in minority populations, it is necessary for interventions to focus on improving awareness, risk-perception, and family and patient-provider communication., Conclusion: Multi-level and targeted interventions are needed to reduce persistent racial/ethnic disparities and improve assessment, provider recommendations, counseling and testing among minority populations.

We examined what proportion of the U.S. population with no personal cancer history reported receiving either genetic counseling or genetic testing for cancer risk, and also the association of these behaviors with cancer risk perceptions. We used data from the 2015 National Health Interview Survey. Objective relative risk scores for breast (women) and colorectal (men and women) cancer risk were generated for individuals without a personal history of cancer. Participants' risk perceptions were compared with their objective relative risk. Of 12,631 women, 1.2% reported receiving genetic counseling and 0.8% genetic testing for hereditary breast cancer risk. Of 15,085 men and women, 0.8% reported receiving genetic counseling and 0.3% genetic testing for hereditary colorectal cancer risk. Higher breast cancer risk perception was associated with genetic counseling (OR: 4.31, 95%CI: 2.56, 7.26) and testing (OR: 3.56, 95%CI: 1.80, 7.03). Similarly, higher perception of colorectal cancer risk was associated with genetic counseling (OR: 5.04, 95%CI: 2.57, 9.89) and testing (OR: 5.92, 95%CI: 2.40, 14.63). A higher proportion of individuals with colorectal cancer risk perceptions concordant with their objective risk (vs. discordant) had undergone genetic counseling or testing for colorectal cancer risk. Concordant risk perceptions for breast cancer were not associated with breast cancer genetic counseling or testing. Given frequent dialogue about implementing population level programs involving genetic services for cancer risk, policy makers and investigators should consider the role of risk perceptions in the effectiveness and design of such programs and potential strategies for addressing inaccuracies in risk perceptions., (Copyright © 2019. Published by Elsevier Inc.)

The prenatal genetic counseling process may be influenced by the patient's insurance coverage for both prenatal testing and termination. Major commercial insurance providers have different policies. TRICARE is the United States Department of Defense health program for uniformed service members. TRICARE provides coverage to approximately 9.4 million beneficiaries, including health plans, special programs, prescriptions, and dental plans. TRICARE's covered medical expenses are outlined in their policies, including those pertaining to genetic testing and termination. This qualitative study aimed to explore the extent to which insurance coverage of prenatal genetic testing and termination of pregnancy affect the genetic counseling process by exploring genetic counselors' experience with TRICARE. The majority of counselors stated that they did not change their overall counseling process for TRICARE patients. However, several counselors expressed that they changed the way they discussed cost with TRICARE patients, specifically in regard to genetic testing. Additionally, counselors provided their perceptions of their patients' emotional experiences. With the recent consolidation of the three TRICARE regions into two TRICARE Regional Office (TRO) regions and the renewal of the Laboratory Developed Tests Demonstration Project, the findings of this study are valuable in the evaluation of TRICARE's coverage of prenatal genetic services., (© 2019 John Wiley & Sons, Ltd.)