Genetic testing in prostate cancer management: Considerations informing primary care.

Inherited genetic mutations can significantly increase the risk for prostate cancer (PC), may be associated with aggressive disease and poorer outcomes, and can have hereditary cancer implications for men and their families. Germline genetic testing (hereditary cancer genetic testing) is now strongly recommended for patients with advanced/metastatic PC, particularly given the impact on targeted therapy selection or clinical trial options, with expanded National Comprehensive Cancer Network guidelines and endorsement from multiple professional societies. Furthermore, National Comprehensive Cancer Network guidelines recommend genetic testing for men with PC across the stage and risk spectrum and for unaffected men at high risk for PC based on family history to identify hereditary cancer risk. Primary care is a critical field in which providers evaluate men at an elevated risk for PC, men living with PC, and PC survivors for whom germline testing may be indicated. Therefore, there is a critical need to engage and educate primary care providers regarding the role of genetic testing and the impact of results on PC screening, treatment, and cascade testing for family members of affected men. This review highlights key aspects of genetic testing in PC, the role of clinicians, with a focus on primary care, the importance of obtaining a comprehensive family history, current germline testing guidelines, and the impact on precision PC care. With emerging evidence and guidelines, clinical pathways are needed to facilitate integrated genetic education, testing, and counseling services in appropriately selected patients. There is also a need for providers to understand the field of genetic counseling and how best to collaborate to enhance multidisciplinary patient care.

Using implementation science to evaluate a population-wide genomic screening program: Findings from the first 20,000 In Our DNA SC participants.

We use the implementation science framework RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) to describe outcomes of In Our DNA SC, a population-wide genomic screening (PWGS) program. In Our DNA SC involves participation through clinical appointments, community events, or at home collection. Participants provide a saliva sample that is sequenced by Helix, and those with a pathogenic variant or likely pathogenic variant for CDC Tier 1 conditions are offered free genetic counseling. We assessed key outcomes among the first cohort of individuals recruited. Over 14 months, 20,478 participants enrolled, and 14,053 samples were collected. The majority selected at-home sample collection followed by clinical sample collection and collection at community events. Participants were predominately female, White (self-identified), non-Hispanic, and between the ages of 40-49. Participants enrolled through community events were the most racially diverse and the youngest. Half of those enrolled completed the program. We identified 137 individuals with pathogenic or likely pathogenic variants for CDC Tier 1 conditions. The majority (77.4%) agreed to genetic counseling, and of those that agreed, 80.2% completed counseling. Twelve clinics participated, and we conducted 108 collection events. Participants enrolled at home were most likely to return their sample for sequencing. Through this evaluation, we identified facilitators and barriers to implementation of our state-wide PWGS program. Standardized reporting using implementation science frameworks can help generalize strategies and improve the impact of PWGS.

The BabySeq Project: A clinical trial of genome sequencing in a diverse cohort of infants.

Efforts to implement and evaluate genome sequencing (GS) as a screening tool for newborns and infants are expanding worldwide. The first iteration of the BabySeq Project (2015-2019), a randomized controlled trial of newborn sequencing, produced novel evidence on medical, behavioral, and economic outcomes. The second iteration of BabySeq, which began participant recruitment in January 2023, examines GS outcomes in a larger, more diverse cohort of more than 500 infants up to one year of age recruited from pediatric clinics at several sites across the United States. The trial aims for families who self-identify as Black/African American or Hispanic/Latino to make up more than 50% of final enrollment, and key aspects of the trial design were co-developed with a community advisory board. All enrolled families receive genetic counseling and a family history report. Half of enrolled infants are randomized to receive GS with comprehensive interpretation of pathogenic and likely pathogenic variants in more than 4,300 genes associated with childhood-onset and actionable adult-onset conditions, as well as larger-scale chromosomal copy number variants classified as pathogenic or likely pathogenic. GS result reports include variants associated with disease (Mendelian disease risks) and carrier status of autosomal-recessive and X-linked disorders. Investigators evaluate the utility and impacts of implementing a GS screening program in a diverse cohort of infants using medical record review and longitudinal parent surveys. In this perspective, we describe the rationale for the second iteration of the BabySeq Project, the outcomes being assessed, and the key decisions collaboratively made by the study team and community advisory board.

The NYCKidSeq randomized controlled trial: Impact of GUÍA digitally enhanced genetic results disclosure in diverse families.

Digital solutions are needed to support rapid increases in the application of genetic/genomic tests (GTs) in diverse clinical settings and patient populations. We developed GUÍA, a bilingual digital application that facilitates disclosure of GT results. The NYCKidSeq randomized controlled trial enrolled diverse children with neurologic, cardiac, and immunologic conditions who underwent GTs. The trial evaluated GUÍA's impact on understanding the GT results by randomizing families to results disclosure genetic counseling with GUÍA (intervention) or standard of care (SOC). Parents/legal guardians (participants) completed surveys at baseline, post-results disclosure, and 6 months later. Survey measures assessed the primary study outcomes of participants' perceived understanding of and confidence in explaining their child's GT results and the secondary outcome of objective understanding. The analysis included 551 diverse participants, 270 in the GUÍA arm and 281 in SOC. Participants in the GUÍA arm had significantly higher perceived understanding post-results (OR = 2.8, CI[1.004, 7.617], p = 0.049) and maintained higher objective understanding over time (OR = 1.1, CI[1.004, 1.127], p = 0.038) compared to SOC. There was no impact on perceived confidence. Hispanic/Latino(a) individuals in the GUÍA arm maintained higher perceived understanding (OR = 3.9, CI[1.603, 9.254], p = 0.003), confidence (OR = 2.7, CI[1.021, 7.277], p = 0.046), and objective understanding (OR = 1.1, CI[1.009, 1.212], p = 0.032) compared to SOC. This trial demonstrates that GUÍA positively impacts understanding of GT results in diverse parents of children with suspected genetic conditions and builds a case for utilizing GUÍA to deliver complex results. Continued development and evaluation of digital applications in diverse populations are critical for equitably scaling GT offerings in specialty clinics.

Personalized genetic counseling for Stargardt disease: Offspring risk estimates based on variant severity.

Recurrence risk calculations in autosomal recessive diseases are complicated when the effect of genetic variants and their population frequencies and penetrances are unknown. An example of this is Stargardt disease (STGD1), a frequent recessive retinal disease caused by bi-allelic pathogenic variants in ABCA4. In this cross-sectional study, 1,619 ABCA4 variants from 5,579 individuals with STGD1 were collected and categorized by (1) severity based on statistical comparisons of their frequencies in STGD1-affected individuals versus the general population, (2) their observed versus expected homozygous occurrence in STGD1-affected individuals, (3) their occurrence in combination with established mild alleles in STGD1-affected individuals, and (4) previous functional and clinical studies. We used the sum allele frequencies of these severity categories to estimate recurrence risks for offspring of STGD1-affected individuals and carriers of pathogenic ABCA4 variants. The risk for offspring of an STGD1-affected individual with the "severe|severe" genotype or a "severe|mild with complete penetrance" genotype to develop STGD1 at some moment in life was estimated at 2.8%-3.1% (1 in 36-32 individuals) and 1.6%-1.8% (1 in 62-57 individuals), respectively. The risk to develop STGD1 in childhood was estimated to be 2- to 4-fold lower: 0.68%-0.79% (1 in 148-126) and 0.34%-0.39% (1 in 296-252), respectively. In conclusion, we established personalized recurrence risk calculations for STGD1-affected individuals with different combinations of variants. We thus propose an expanded genotype-based personalized counseling to appreciate the variable recurrence risks for STGD1-affected individuals. This represents a conceptual breakthrough because risk calculations for STGD1 may be exemplary for many other inherited diseases.

A Randomized Trial of Two Remote Health Care Delivery Models on the Uptake of Genetic Testing and Impact on Patient-Reported Psychological Outcomes in Families With Pancreatic Cancer: The Genetic Education, Risk Assessment, and Testing (GENERATE) Study.

BACKGROUND & AIMS: Genetic testing uptake for cancer susceptibility in family members of patients with cancer is suboptimal. Among relatives of patients with pancreatic ductal adenocarcinoma (PDAC), The GENetic Education, Risk Assessment, and TEsting (GENERATE) study evaluated 2 online genetic education/testing delivery models and their impact on patient-reported psychological outcomes. METHODS: Eligible participants had ≥1 first-degree relative with PDAC, or ≥1 first-/second-degree relative with PDAC with a known pathogenic germline variant in 1 of 13 PDAC predisposition genes. Participants were randomized by family, between May 8, 2019, and June 1, 2021. Arm 1 participants underwent a remote interactive telemedicine session and online genetic education. Arm 2 participants were offered online genetic education only. All participants were offered germline testing. The primary outcome was genetic testing uptake, compared by permutation tests and mixed-effects logistic regression models. We hypothesized that Arm 1 participants would have a higher genetic testing uptake than Arm 2. Validated surveys were administered to assess patient-reported anxiety, depression, and cancer worry at baseline and 3 months postintervention. RESULTS: A total of 424 families were randomized, including 601 participants (n = 296 Arm 1; n = 305 Arm 2), 90% of whom completed genetic testing (Arm 1 [87%]; Arm 2 [93%], P = .014). Arm 1 participants were significantly less likely to complete genetic testing compared with Arm 2 participants (adjusted ratio [Arm1/Arm2] 0.90, 95% confidence interval 0.78-0.98). Among participants who completed patient-reported psychological outcomes questionnaires (Arm 1 [n = 194]; Arm 2 [n = 206]), the intervention did not affect mean anxiety, depression, or cancer worry scores. CONCLUSIONS: Remote genetic education and testing can be a successful and complementary option for delivering genetics care. (Clinicaltrials.gov, number NCT03762590).

Parkinson's disease variant detection and disclosure: PD GENEration, a North American study.

Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson's disease; however, individuals with Parkinson's disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson's disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson's disease. PD GENEration is an ongoing multi-centre, observational study (NCT04057794, NCT04994015) offering genetic testing with results disclosure and genetic counselling to those in the US (including Puerto Rico), Canada and the Dominican Republic, through local clinical sites or remotely through self-enrolment. DNA samples are analysed by next-generation sequencing including deletion/duplication analysis (Fulgent Genetics) with targeted testing of seven major Parkinson's disease-related genes. Variants classified as pathogenic/likely pathogenic/risk variants are disclosed to all tested participants by either neurologists or genetic counsellors. Demographic and clinical features are collected at baseline visits. Between September 2019 and June 2023, the study enrolled 10 510 participants across >85 centres, with 8301 having received results. Participants were: 59% male; 86% White, 2% Asian, 4% Black/African American, 9% Hispanic/Latino; mean age 67.4 ± 10.8 years. Reportable genetic variants were observed in 13% of all participants, including 18% of participants with one or more 'high risk factors' for a genetic aetiology: early onset (<50 years), high-risk ancestry (Ashkenazi Jewish/Basque/North African Berber), an affected first-degree relative; and, importantly, in 9.1% of people with none of these risk factors. Reportable variants in GBA1 were identified in 7.7% of all participants; 2.4% in LRRK2; 2.1% in PRKN; 0.1% in SNCA; and 0.2% in PINK1, PARK7 or VPS35 combined. Variants in more than one of the seven genes were identified in 0.4% of participants. Approximately 13% of study participants had a reportable genetic variant, with a 9% yield in people with no high-risk factors. This supports the promotion of universal access to genetic testing for Parkinson's disease, as well as therapeutic trials for GBA1 and LRRK2-related Parkinson's disease.

Guidelines for NGS procedures applied to prenatal diagnosis by the Spanish Society of Gynecology and Obstetrics and the Spanish Association of Prenatal Diagnosis.

OBJECTIVE: This document addresses the clinical application of next-generation sequencing (NGS) technologies for prenatal genetic diagnosis and aims to establish clinical practice recommendations in Spain to ensure uniformity in implementing these technologies into prenatal care. METHODS: A joint committee of expert obstetricians and geneticists was created to review the existing literature on fetal NGS for genetic diagnosis and to make recommendations for Spanish healthcare professionals. RESULTS: This guideline summarises technical aspects of NGS technologies, clinical indications in prenatal setting, considerations regarding findings to be reported, genetic counselling considerations as well as data storage and protection policies. CONCLUSIONS: This document provides updated recommendations for the use of NGS diagnostic tests in prenatal diagnosis. These recommendations should be periodically reviewed as our knowledge of the clinical utility of NGS technologies, applied during pregnancy, may advance.

Survey of service needs to embed genome sequencing for motor neuron disease in neurology in the English National Health Service.

All people with motor neuron disease (pwMND) in England are eligible for genome sequencing (GS), with panel-based testing. With the advent of genetically targeted MND treatments, and increasing demand for GS, it is important that clinicians have the knowledge and skills to support pwMND in making informed decisions around GS. We undertook an online survey of clinical genomic knowledge and genetic counselling skills in English clinicians who see pwMND. There were 245 respondents to the survey (160 neurology clinicians and 85 genetic clinicians). Neurology clinicians reported multiple, overlapping barriers to offering pwMND GS. Lack of time to discuss GS in clinic and lack of training in genetics were reported. Neurology clinicians scored significantly less well on self-rated genomic knowledge and genetic counselling skills than genetic clinicians. The majority of neurology clinicians reported that they do not have adequate educational or patient information resources to support GS discussions. We identify low levels of genomic knowledge and skills in the neurology workforce. This may impede access to GS and precision medicine for pwMND.

Expanded targeted preconception screening panel in Israel: findings and insights.

BACKGROUND: We aimed to analyse the efficacy and added value of a targeted Israeli expanded carrier screening panel (IL-ECSP), beyond the first-tier test covered by the Israeli Ministry of Health (IMOH) and the second-tier covered by the Health Maintenance Organisations (HMOs). METHODS: A curated variant-based IL-ECSP, tailored to the uniquely diverse Israeli population, was offered at two tertiary hospitals and a major genetics laboratory. The panel includes 1487 variants in 357 autosomal recessive and X-linked genes. RESULTS: We analysed 10 115 Israeli samples during an 18-month period. Of these, 6036 (59.7%) were tested as couples and 4079 (40.3%) were singles. Carriers were most frequently identified with mutations in the following genes: GJB2/GJB6 (1:22 allele frequency), CFTR (1:28), GBA (1:34), TYR (1:39), PAH (1:50), SMN1 (1:52) and HEXA (1:56). Of 3018 couples tested, 753 (25%) had no findings, in 1464 (48.5%) only one partner was a carrier, and in 733 (24.3%) both were carriers of different diseases. We identified 79 (2.6%) at-risk couples, where both partners are carriers of the same autosomal recessive condition, or the female carries an X-linked disease. Importantly, 48.1% of these would not have been detected by ethnically-based screening tests currently provided by the IMOH and HMOs, for example, variants in GBA, TYR, PAH and GJB2/GJB6. CONCLUSION: This is the largest cohort of targeted ECSP testing, tailored to the diverse Israeli population. The IL-ECSP expands the identification of couples at risk and empowers their reproductive choices. We recommend endorsing an expanded targeted panel to the National Genetic Carrier Screening programme.

The Role of Genetic Testing in Adult CKD.

Mounting evidence indicates that monogenic disorders are the underlying cause in a significant proportion of patients with CKD. In recent years, the diagnostic yield of genetic testing in these patients has increased significantly as a result of revolutionary developments in genetic sequencing techniques and sequencing data analysis. Identification of disease-causing genetic variant(s) in patients with CKD may facilitate prognostication and personalized management, including nephroprotection and decisions around kidney transplantation, and is crucial for genetic counseling and reproductive family planning. A genetic diagnosis in a patient with CKD allows for screening of at-risk family members, which is also important for determining their eligibility as kidney transplant donors. Despite evidence for clinical utility, increased availability, and data supporting the cost-effectiveness of genetic testing in CKD, especially when applied early in the diagnostic process, many nephrologists do not use genetic testing to its full potential because of multiple perceived barriers. Our aim in this article was to empower nephrologists to (further) implement genetic testing as a diagnostic means in their clinical practice, on the basis of the most recent insights and exemplified by patient vignettes. We stress why genetic testing is of significant clinical benefit to many patients with CKD, provide recommendations for which patients to test and which test(s) to order, give guidance about interpretation of genetic testing results, and highlight the necessity for and essential components of pretest and post-test genetic counseling.

Scaling Genetic Counseling in the Genomics Era.

The development of massively parallel sequencing-based genomic sequencing tests has increased genetic test availability and access. The field and practice of genetic counseling have adapted in response to this paradigm-shifting technology and the subsequent transition to practicing genomic medicine. While the key elements defining genetic counseling remain relevant, genetic counseling service delivery models and practice settings have evolved. Genetic counselors are addressing the challenges of direct-to-consumer and consumer-driven genetic testing, and genetic counseling training programs are responding to the ongoing increased demand for genetic counseling services across a broadening range of contexts. The need to diversify both the patient and participant groups with access to genetic information, as well as the field of genetic counseling, is at the forefront of research and training program initiatives. Genetic counselors are key stakeholders in the genomics era, and their contributions are essential to effectively and equitably deliver precision medicine.

What do cancer genetic providers want us to know about variant reclassification and recontact that we are not asking? A thematic analysis of open-ended survey responses.

BACKGROUND: Accurate variant classification and relaying reclassified results to patients is critical for hereditary cancer care delivery. Over a 5- to 10-year period, 6%-15% of variants undergo reclassification. As the frequency of reclassifications increases, the issue of whether, how, when, and which providers should recontact patients becomes important but remains contentious. METHODS: The authors used inductive thematic analysis to analyze open-ended comments offered by oncologists and genetic counselors (GCs) from a large national survey. RESULTS: Of the 634 oncologists and cancer GCs, 126 (20%) offered substantive free-text comments. Four thematic areas emerged: 1) ambiguity over professional responsibility to recontact, 2) logistical challenges with recontact, 3) importance of inter-institutional communication, and 4) suggested solutions. Some oncologists felt that laboratories, not them, are responsible for recontact; others believed that ordering providers/GCs were responsible; GCs readily acknowledged their own responsibility in recontact but added important caveats. Besides the lack of up-to-date patient contact information, providers raised unique challenges with recontact: financial instability of laboratories, lack of clinical resources, contacting family members, and accumulating burden of reclassifications. There were numerous calls for developing practice guidelines on prioritizing variants for recontact and discussion on whether duty for recontact may be fulfilled via unidirectional, low touch modalities. Potential solutions to recontact including national databases and patient facing databases were discussed. CONCLUSIONS: The authors confirm previous themes of stakeholder opinions and add previously unreported contextual details to qualify those themes. Clarifying provider responsibilities through professional guidelines for reclassification and recontact addressing the subthemes identified here will better serve all constituencies.

Joint ABS-UKCGG-CanGene-CanVar consensus regarding the use of CanRisk in clinical practice.

BACKGROUND: The CanRisk tool, which operationalises the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) is used by Clinical Geneticists, Genetic Counsellors, Breast Oncologists, Surgeons and Family History Nurses for breast cancer risk assessments both nationally and internationally. There are currently no guidelines with respect to the day-to-day clinical application of CanRisk and differing inputs to the model can result in different recommendations for practice. METHODS: To address this gap, the UK Cancer Genetics Group in collaboration with the Association of Breast Surgery and the CanGene-CanVar programme held a workshop on 16th of May 2023, with the aim of establishing best practice guidelines. RESULTS: Using a pre-workshop survey followed by structured discussion and in-meeting polling, we achieved consensus for UK best practice in use of CanRisk in making recommendations for breast cancer surveillance, eligibility for genetic testing and the input of available information to undertake an individualised risk assessment. CONCLUSIONS: Whilst consensus recommendations were achieved, the meeting highlighted some of the barriers limiting the use of CanRisk in clinical practice and identified areas that require further work and collaboration with relevant national bodies and policy makers to incorporate wider use of CanRisk into routine breast cancer risk assessments.

Development of an Electronic Decision Aid Tool to Facilitate Mainstream Genetic Testing in Ovarian Cancer Patients.

BACKGROUND: Multigene panel testing is an important component of cancer treatment plans and risk assessment, but there are many different panel options and choosing the most appropriate panel can be challenging for health care providers and patients. Electronic tools have been proposed to help patients make informed decisions about which gene panel to choose by considering their preferences and priorities. MATERIALS AND METHODS: An electronic decision aid (DA) tool was developed in line with the International Patient Decision Aids Standards collaboration. The multidisciplinary project team collaborated with an external health care communications agency and the MGH Cancer Center Patient and Family Advisory Council (PFAC) to develop the DA. Surveys of genetic counselors and patients were used to scope the content, and alpha testing was used to refine the design and content. RESULTS: Surveys of genetic counselors (n = 12) and patients (n = 228) identified common themes in discussing panel size and strategies for helping patients decide between panels and in identifying confusing terms for patients and distribution of patients' choices. The DA, organized into 2 major sections, provides educational text, graphics, and videos to guide patients through the decision-making process. Alpha testing feedback from the PFAC (n = 4), genetic counselors (n = 3) and a group of lay people (n = 8) identified areas to improve navigation, simplify wording, and improve layout. CONCLUSION: The DA developed in this study has the potential to facilitate informed decision-making by patients regarding cancer genetic testing. The distinctive feature of this DA is that it addresses the specific question of which multigene panel may be most suitable for the patient. Its acceptability and effectiveness will be evaluated in future studies.

The sufficiency of genetic diagnosis in managing patients with inborn errors of immunity during prenatal care and childbearing.

Individuals with inborn errors of immunity face challenges in fertility, pregnancy, and genetic disorder transmission. Prenatal genetic counseling is crucial, especially in tribal societies with consanguineous unions. Ten families with confirmed inborn errors of immunity were studied, revealing diverse pregnancy decisions: An architect with autosomal dominant STAT-1 gain of function underwent prenatal diagnosis despite initial plans for preimplantation genetic diagnosis. In a consanguineous family, two children died from leukocyte adhesion deficiency type 1 because the father refused prenatal diagnosis. First cousins opted against terminating the second pregnancy, resulting in two children affected by Bruton disease. Another consanguineous couple, with two children afflicted by ataxia-telangiectasia, chose oocyte donation for their third child, ensuring a healthy birth. Recurrent pregnancy loss was observed in a mother subsequently diagnosed with ZAP70 deficiency. A mother with Wiskott-Aldrich syndrome child opted for in vitro fertilization, leading to a healthy birth post-prenatal diagnosis. A misdiagnosis of anaplastic anemia occurred in a family with multiple instances of Wiskott-Aldrich syndrome. A leukocyte adhesion deficiency type 1 case led to parental dissolution due to the father's refusal to acknowledge the condition. In a non-consanguineous couple, the father's diagnosis of TACI deficiency influenced the mother's decision to discontinue pregnancy post-prenatal diagnosis. Genetic diagnosis alone cannot optimize prenatal care for immune dysregulation disorders. Various factors, including patient education, societal norms, ethics, and economics, impact pregnancy decisions. Clinical immunologists must integrate these elements into guidance strategies to enhance patient outcomes.

Information needs persist after genetic counseling and testing for BRCA1/2 and Lynch Syndrome.

PURPOSE: Research has shown that cancer genetic risk is often not well understood by patients undergoing genetic testing and counseling. We describe the barriers to understanding genetic risk and the needs of high-risk persons and cancer survivors who have undergone genetic testing. METHODS: Using data from an internet survey of adults living in the USA who responded 'yes' to having ever had a genetic test to determine cancer risk (N = 696), we conducted bivariate analyses and multivariable logistic regression models to evaluate associations between demographic, clinical, and communication-related variables by our key outcome of having vs. not having enough information about genetics and cancer to speak with family. Percentages for yes and no responses to queries about unmet informational needs were calculated. Patient satisfaction with counseling and percentage disclosure of genetic risk status to family were also calculated. RESULTS: We found that a lack of resources provided by provider to inform family members and a lack of materials provided along with genetic test results were strongly associated with not having enough information about genetics and cancer (OR 4.54 95% CI 2.40-8.59 and OR 2.19 95% CI 1.16-4.14 respectively). Among participants undergoing genetic counseling, almost half reported needing more information on what genetic risk means for them and their family and how genetic testing results might impact future screening. CONCLUSION: High levels of satisfaction with genetic counseling may not give a full picture of the patient-provider interaction and may miss potential unmet needs of the patient. Accessible resources and ongoing opportunities for updating family history information could reinforce knowledge about genetic risk.

Retrospective genetic testing (Traceback) in women with early-onset breast cancer after revised national guidelines: a clinical implementation study.

PURPOSE: This study focused on identifying a hereditary predisposition in women previously diagnosed with early-onset breast cancer through a retrospective outreach activity (Traceback). The objectives were to evaluate the possible clinical implementation of a simplified Traceback strategy and to identify carriers of pathogenic variants among previously untested women. METHODS: Three hundred and fifteen Traceback-eligible women diagnosed with breast cancer at 36-40 years in Southern Sweden between 2000 and 2019 were identified and offered an analysis of the genes ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, and RAD51D through a standardized letter. Women who chose to participate were asked about their experiences through a questionnaire. The workload for the study personnel was measured and recorded. RESULTS: One hundred and seventy-six women underwent genetic testing and pathogenic variants were identified in 9.7%: ATM (n = 6), BARD1 (n = 1), BRCA1 (n = 3), CHEK2 (n = 5), and PALB2 (n = 2). Women with normal test results were informed through a standardized letter. Carriers of pathogenic variants were contacted by telephone and offered in-person genetic counseling. One hundred and thirty-four women returned the subsequent questionnaire. Most study participants were satisfied with both written pre- and post-test information and many expressed their gratitude. The extra workload as compared to routine clinical genetic counseling was modest (8 min per patient). CONCLUSION: The insights from the participants' perspectives and sentiments throughout the process support the notion that the Traceback procedure is a safe and an appreciated complement to routine genetic counseling. The genetic yield of almost 10% also suggests that the associated extra workload for genetic counselors could be viewed as acceptable in clinical implementation scenarios.

Universal genetic counseling in breast cancer patients significantly improves overall testing rates and improves completion rates in subpopulations.

PURPOSE: The NCCN guidelines recommend genetic testing in those patients at increased risk of breast cancer in order to identify candidates for increased frequency of screening or prophylactic mastectomy. However, genetic testing may now identify patients who may benefit from recently developed targeted breast cancer therapy. In order to more widely identify these patients, we implemented genetic counseling for all patients diagnosed with breast cancer. METHODS: In 2021, all patients evaluated within a Midwestern community hospital system diagnosed with breast cancer were offered genetic counseling. This group of patients was compared to a cohort of patients in 2021 who were offered genetic counseling based on NCCN guidelines. With Pearson's chi square, Fisher's Exact test, Mann-Whitney U, and multivariate regression as appropriate, individual demographic data and genetic testing completion between 2019 and 2021 were evaluated. RESULTS: A total of 973 patients were reviewed. 439 were diagnosed with breast cancer in 2019 and 534 in 2021. Demographics and stage at diagnosis (p = 0.194) were similar between years. Completion of genetic testing increased from 204 (46.5%) in 2019 to 338 (63.3%) in 2021 (p < 0.01) with the universal counseling protocol. Specifically, genetic testing completion increased significantly in older patients (p = 0.041) and patients receiving Medicare benefits (p = 0.005). The overall pathogenic variants found increased from 32 to 39 with the most common including BRCA2 (n = 11), CFTR (n = 9), CHEK2 (n = 8), BRCA1 (n = 6). CONCLUSION: Universal genetic counseling was related to a significant increase in genetic testing completion and an increase in pathogenic variants found among breast cancer patients, specifically in subpopulations which may have been previously excluded by traditional NCCN genetic testing screening guidelines.