Genetic Cancer Risk Assessment Research Articles

Abstract PO3-09-04: Identification of germline pathogenic variants to guide systemic therapy: Prevalence and spectrum of PVs among Mexican patients with metastatic breast cancer

Abstract BACKGROUND Currently, international genetic cancer risk assessment (GCRA) guidelines recommend genetic testing for the identification of germline pathogenic variants (PVs) in patients with metastatic breast cancer (MBC) to guide systemic therapy. Patients with PVs in BRCA genes are candidates to receive poly(adenosine diphosphate–ribose) polymerase inhibitors (PARPi). The prevalence of PVs in patients with HER2-negative MBC has been reported to be 10%. The proportion of MBC in low- and middle-income countries (LMIC) is higher. However, access to genetic testing in LMIC is limited and contributes to the gap in genetic epidemiology knowledge. We aimed to describe the frequency of germline PVs in breast cancer associated genes and clinic-pathologic characteristics of Mexican women with MBC. METHODS This retrospective study included Mexican women from 7 centers in Mexico, who were diagnosed with MBC and had genetic testing. Pathogenic and likely pathogenic variants were reported. Demographic, histopathological characteristics, family history and access to treatment with PARPi, were obtained from chart review. RESULTS From August 2017 to May 2023, 114 Mexican women with MBC were included, median age at diagnosis was 47 years (range 24-80 y), 42% had de novo metastatic, and 58% recurrent disease. 86.8% had infiltrating ductal carcinoma, 51.3% had HR+HER2- (n=58), 4.4% HR+HER+ (n=5), 5.3% HR-HER2+ (n=6), and 38.6% triple negative tumors (n=44). Sites of metastatic disease were as follows: 61.4% non-regional nodes (n=70), 57% bone (n=65), 40.3% lung (n=46), 30.7% liver (n=35), 15.8% central nervous system (n=18) and 7% peritoneal carcinomatosis (n=8). The frequency of PVs was 22% (25/114); 84% of the PVs were heterozygous, mainly identified in BRCA genes (BRCA1 n=12, BRCA2 n=9), and in 4 patients in other genes (PALB2 n=2, PTEN n=1, MUTYH n=1). Among PARPi candidates, 40% (10/25) received Olaparib, the majority received it on the second or subsequent lines of treatment (7/10) with a median progression free survival of 6 months (3-13 m). BRCA carriers were younger at BC diagnosis (38.5 vs. 49 years, p=0.00694) and had a significant higher proportion of family history of ovarian cancer (p=0.00039), but not for breast (p=0.06), prostate (p=0.71) or pancreatic cancer (p=0.098), compared to non-carriers. CONCLUSION We found a high frequency of PVs in BRCA genes in Mexican women with MBC. Access to the genetic testing and targeted therapy should be improve in the Mexican population in order to decrease disparities in cancer care in the Mexican Population. In addition, genetic testing allows to identify other family members at risk with cascade testing and to recommend them risk reduction strategies. Citation Format: Jose Luis Rodriguez-Olivares, Maria Fernanda Esparza-Orozco, Jose Alfredo Ramirez-Gonzalez, Roberto Ivan Sanchez-Reyes, Enrique Isay Talamantes-Gamez, Gregorio Quintero-Beulo, Gilberto Lopez-Rosas, Karla Alicia Centelles-López, Brizio Moreno-Jaime, Daniela Vazquez-Juarez, Ana Maria Hernandez-Murillo, Ilana de la Puente Tawil, Jeffrey Weitzel, Cynthia Villareal Garza, Yanin Chavarri-Guerra. Identification of germline pathogenic variants to guide systemic therapy: Prevalence and spectrum of PVs among Mexican patients with metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-09-04.

Uptake of Risk-Reducing Measures, Cascade Testing, and Related Challenges Among Carriers of Breast Cancer-Associated Germline Pathogenic Variants in Mexico.

Genetic cancer risk assessment (GCRA) provides pathogenic variant (PV) carriers with the invaluable opportunity to undertake timely cancer risk-reducing (RR) measures and initiate cascade testing (CT). This study describes the uptake of these strategies and the related barriers among breast cancer-associated germline PV carriers in Mexico. Carriers who were at least 6 months after disclosure of genetic test results at two GCRA referral centers were invited to answer a survey assessing sociodemographic characteristics, awareness of their carrier status and its implications, uptake of RR measures according to international guidelines by PV, CT initiation, and associated challenges. Of the eligible carriers, 246/384 (64%) answered the survey (median age: 44 years). Most were female (88%), married/in domestic partnership (66%), and had personal breast/ovarian cancer history (61%). PVs included BRCA1/2 (75%), CHEK2 (10%), PALB2 (5%), ATM (5%), NF1 (2%), RAD51C (2%), PTEN (1%), and TP53 (1%). Most (87%) participants were aware of their carrier status. When recommended, 37% underwent RR bilateral mastectomy, 48% RR oophorectomy, 70% annual mammogram, and 20% breast magnetic resonance imaging. Challenges hindering the uptake of RR measures included financial limitations (67%), lack of recommendation by their physician (35%), and fear (24%). Nearly all (98%) claimed sharing their results with their relatives. CT was initiated in 63% of families and was associated with carriers being married/in domestic partnership (P = .04) and believing GCRA was useful (P < .001). Despite the resource-constrained setting, relevant rates of RR measures and CT were observed. Targeted interventions to reduce out-of-pocket expenses and improve patient-physician communication and patients' understanding on carrier status are warranted to enhance the overall benefit of GCRA and ultimately improve the provision of patient-centered care to both carriers and their at-risk relatives.

Genetic counselors' and community clinicians' implementation and perceived barriers to informed consent during pre-test counseling for hereditary cancer risk.

As demand for genetic cancer risk assessment (GCRA) continues to increase, so does the sense of urgency to scale up efforts to triage patients, facilitate informed consent, and order genetic testing for cancer risk. The National Society of Genetic Counselors outlines the elements of informed consent that should be addressed in a GCRA session. While this practice resource aims to improve health equity, research on how well the elements of informed consent are implemented in practice is lacking. This retrospective and prospective mixed-methods study assessed how adequately the elements of informed consent are addressed during pre-test GCRA among 307 community clinicians (CC) and 129 cancer genetic counselors (GC), and barriers they face to addressing these elements. Results revealed that more than 90% of both cohorts consistently addressed components of at least 5 of the 10 elements of informed consent during a pre-test consultation. Technical aspects and accuracy of the test and utilization of test results were the most similarly addressed elements. Notably, GCs more often review the purpose of the test and who to test, general information about the gene(s), and economic considerations whereas CCs more often review alternatives to testing. Both cohorts reported psychosocial aspects of the informed consent process as the least adequately addressed element. Time constraints and patient-related concerns were most often cited by both cohorts as barriers to optimal facilitation of informed consent. Additional barriers reported by CCs included provider lack of awareness, experience, or education, and availability of resources and institutional support. Findings from this study may contribute to the development of alternative delivery models that incorporate supplementary educational tools to enhance patient understanding about the utility of genetic testing, while helping to mitigate the barrier of time constraints. Equally important is the use of this information to develop continuing education tools for providers.

Retrospective chart analysis to determine the impact of a patient-facing digital risk stratification tool combined with a clinical screener for hereditary cancer genetic risk assessment triage in a community oncology clinic.

The purpose of this study was to evaluate the utility of adding a clinical screener to the patient-facing digital risk stratification tool triage process for the identification of patients eligible for a genetic risk assessment for hereditary cancer. Digital risk stratification entries were retrospectively reviewed to determine the overall number of patients eligible for genetic risk assessment. These were also analyzed to determine how many patients were re-contacted by the clinical screener, and how many of those recontacted patients met criteria after their personal and family history was revised by the clinical screener. There was an 89.9% digital risk stratification triage tool completion rate, with 22.6% requiring contact from the clinical screener. Of the 640 patients who completed the digital tool, 5.9% met criteria for testing after their personal and/or family history was revised by the clinical screener. Overall, 51.1% of patients met criteria for a genetic risk assessment. The addition of a clinical screener further increased identification of patients eligible for genetic risk assessment. About half of patients who met criteria after being contacted by the clinical screener met criteria based on their personal diagnosis of cancer alone. Incorporation of a clinical screener to the digital screening process may serve to reduce barriers to patient completion of the tool and increase rates of patient identification for cancer genetic services.

Hereditary cancer testing in a diverse sample across three breast imaging centers

PurposeUp to 10% of all breast cancers (BC) are attributed to inherited pathogenic variants (PV) in BC susceptibility genes; however, most carriers of PVs remain unidentified. Here, we sought to determine the yield of hereditary cancer gene PVs among diverse women attending breast imaging centers, who could benefit from enhanced surveillance and/or risk reduction interventions.MethodsThis cross-sectional retrospective cohort study included consecutive women, unselected for personal or family cancer history, who were offered genetic testing for hereditary cancer genes at the time of breast imaging at three centers (November 2020–March 2022).ResultsAmong 1943 patients (median age: 66 years), self-reported race/ethnicity was White (34.5%), Hispanic (27.7%), African American (17.9%), Asian (4.5%), Ashkenazi Jewish (0.6%), Other (3.5%), and missing (13.0%). Thirty-nine patients (2%) were identified as carriers of a PV in an autosomal dominant clinically actionable hereditary breast and ovarian cancer (HBOC)-related or Lynch syndrome gene, most frequently, BRCA2 (6/39; 15.4%), PALB2 (8/39; 20.5%), CHEK2 (10/39; 25.6%), and PMS2 (5/39; 12.8%). Of the 34 PVs with known race/ethnicity, 47% were detected among non-White patients. Overall, 354/1,943 (18.2%) of patients met NCCN guidelines for HBOC gene testing and only 15/39 (38.5%) patients with an autosomal dominant clinically actionable PV met guidelines.ConclusionThis population health approach extended the reach of genetic cancer risk assessment in a diverse population and highlighted the limits of a guideline-based approach. This may help address inequity in access to risk-appropriate screening and cancer prevention.

Genetic cancer risk assessment for PA practice.

The roles of cancer genetics and risk assessment as areas of medicine are rapidly evolving. Genetic cancer risk assessment (GCRA) has begun to penetrate patient care for providers in all specialties and areas of expertise. To provide comprehensive patient care and thorough risk evaluation, physician associates/assistants (PAs) should have a fundamental understanding of the role of GCRA as it pertains to their patients' overall health and medical management. This article highlights the importance of GCRA services, outlines resources for PAs to gain proficiency in GCRA, and provides a walkthrough of GCRA practice development and maintenance.

Familial genetic cancer risk assessment in a male patient with pancreatic and breast cancer with a silent BRCA2 mutation

Male breast cancer (MBC) is relatively rare, accounting for &lt;1% of cancers in men. Hereditary MBC is mainly attributed to BRCA1/2 germline mutations. Accordingly, National Comprehensive Cancer Network guidelines advise genetic counseling and testing for all cases of MBCs and their unaffected family members. In this report, we present an uncommon case of a male patient in his late 50s primarily diagnosed with pancreatic cancer who later developed asynchronous bilateral hormone-positive breast cancer. Genetic testing revealed a “pathogenic/likely pathogenic” BRCA2 variant (c.8754G &gt;A, pE2918E) in the proband. Cascade testing of 34 family members identified 5 of the family members as carriers of this BRCA2 variant. Among them, two members were breast cancer affected and three were unaffected healthy carriers. Our study demonstrates the clinical relevance of this silent BRCA2 mutation and emphasizes the need for further experimental studies to elucidate its functional role in breast cancer pathology.

Chatbot Artificial Intelligence for Genetic Cancer Risk Assessment and Counseling: A Systematic Review and Meta-Analysis.

Most individuals with a hereditary cancer syndrome are unaware of their genetic status to underutilization of hereditary cancer risk assessment. Chatbots, or programs that use artificial intelligence to simulate conversation, have emerged as a promising tool in health care and, more recently, as a potential tool for genetic cancer risk assessment and counseling. Here, we evaluated the existing literature on the use of chatbots in genetic cancer risk assessment and counseling. A systematic review was conducted using key electronic databases to identify studies which use chatbots for genetic cancer risk assessment and counseling. Eligible studies were further subjected to meta-analysis. Seven studies met inclusion criteria, evaluating five distinct chatbots. Three studies evaluated a chatbot that could perform genetic cancer risk assessment, one study evaluated a chatbot that offered patient counseling, and three studies included both functions. The pooled estimated completion rate for the genetic cancer risk assessment was 36.7% (95% CI, 14.8 to 65.9). Two studies included comprehensive patient characteristics, and none involved a comparison group. Chatbots varied as to the involvement of a health care provider in the process of risk assessment and counseling. Chatbots have been used to streamline genetic cancer risk assessment and counseling and hold promise for reducing barriers to genetic services. Data regarding user and nonuser characteristics are lacking, as are data regarding comparative effectiveness to usual care. Future research may consider the impact of chatbots on equitable access to genetic services.

CATCH: Blueprint for a cancer genetic risk assessment tool for use in a diverse, underserved gynecology clinic population (163)

CATCH: Blueprint for a cancer genetic risk assessment tool for use in a diverse, underserved gynecology clinic population (163)

Proactive familial cancer risk assessment: a service development study in UK primary care.

Family history assessment can identify individuals above population-risk for cancer to enable targeted Screening, Prevention, and Early Detection (SPED). Family History Questionnaire Service (FHQS) is a resource-efficient patient-facing online tool to facilitate this. In the UK, cancer risk assessment is usually only offered to concerned individuals proactively self-presenting to their GP, leading to inequity in accessing SPED in the community. To improve access to community cancer genetic risk assessment and explore barriers to uptake. Service development project of a digital pathway using the FHQS for cancer risk assessment across four general practices within the clinical remit of the South West Thames Centre for Genomics (SWTCG). 3100 individuals aged 38-50 years were invited to complete the FHQS through either text message or email. A random selection of 100 non-responders were contacted to determine barriers to uptake. In total, n = 304/3100 (10%) registered for the FHQS. Responders were more likely to be British (63% vs 47%, P<0.001), speak English as their main language (92% vs 76%, P<0.001), and not require an interpreter (99.6% vs 94.9%, P = 0.001). Of 304 responders, 158 (52%) were automatically identified as at population-risk without full family history review. Of the remaining 146 responders, 52 (36%) required either additional screening referral (n = 23), genetics referral (n = 15), and/or advice to relatives (n = 18). Of 100 non-responders contacted, eight had incorrect contact details and 53 were contactable. Reasons for not responding included not receiving invitation details (n = 26), losing the invitation (n = 5), or forgetting (n = 4). The FHQS can be used as part of a low-resource primary care pathway to identify individuals in the community above population-risk for cancer requiring action. This study highlighted barriers to uptake requiring consideration to maximise impact and minimise inequity.

Assessment of medical knowledge toward genetic testing for individuals with hereditary breast and ovarian cancer syndrome in Brazil

Genetic testing has become increasingly used in medical practice to enable genetic cancer risk assessment. In Hereditary Breast and Ovarian Cancer syndrome (HBOC), it can be used to screen pathogenic germline variants. The access to early diagnosis, from the request until the proper interpretation of genetic tests depends on medical knowledge. The aim of this study was to evaluate the knowledge of family physicians, oncologists, geneticists and gynecologists regarding genetic testing for patients with suspected HBOC in Brazil. A cross-sectional survey of physicians was performed using a self-administered questionnaire. One hundred and ninety-two physicians answered the questionnaire (23 were geneticists, 38 gynecologists, 39 family physicians, and 92 oncologists). Only 15.4% of family physicians and 26% of gynecologists feel prepared to order genetic testing for patients with personal and/or family history of breast and/or ovarian cancer. Even though 87% of the oncologists have genetic testing available in their clinical practice, only 51.1% consider they have sufficient knowledge to manage patients after detecting a pathogenic germline variant and 17.4% do not feel comfortable interpreting them. Most oncologists and geneticists are very knowledgeable about recommendations for genetic testing order and management of HBOC patients. On the other hand, gynecologists and family physicians order genetic testing less frequently (28.9% and 7.7%, respectively) and have difficulties interpreting (26.3% and 2.3%, respectively) and managing these patients. These observations raise important issues regarding the implementation of genetic testing in Brazil, including the development of training programs for physicians from different specialties.

Connecting Black families in Houston, Texas, to hereditary cancer genetic counseling, genetic testing, and cascade testing by using a simple cancer genetic risk assessment and telegenetics.

TPS10638 Background: Hereditary breast and colorectal cancers accounts for 5-10% of all cases, but less than half of all eligible patients undergo NCCN guideline-concordant screening. This proportion is even lower among Black patients, who have a higher breast cancer and colorectal incidence and mortality. Recruitment through community organizations has been shown to identify patients who are eligible for genetic testing but have not been offered it by their doctor. Our one-page cancer genetic risk assessment (CGRA) and telegenetics were previously shown to improve adherence to genetic testing guidelines for hereditary breast and ovarian cancer. Our objective is to identify adults eligible for hereditary breast and colorectal cancer syndromes genetic testing using trusted community organizations that serve the Black community as entry points, reach them with our tailored program, and measure impact. Methods: In this prospective single-arm trial, adults of &gt; 18 years old who self-identify as Black or African American are recruited during events put together by community organizations in Houston, Texas. The CGRA was modified to encompass hereditary breast and colorectal cancer syndromes based on NCCN guidelines. To improve convenience, eligible participants can be consented and fill out the CGRA in-person or via QR code link using a smart phone. Study team members attend community events and are also available via phone to help with informed consent, CGRA, etc. Those at high risk for hereditary breast and colorectal cancer syndromes are provided with educational materials and can be sent the saliva-based kit or complete it on-site. When results of genetic testing include a pathogenic mutation (PV) or variant of uncertain significance, individuals receive telegenetic counseling and risk reduction resources, including about cascade genetic testing. Others are notified of negative results. The program includes education for interested community organization members about importance of genetic testing. The program is projected to reach 1,000 participants with 300 completing genetic testing and identification of 11 PV. The study is overseen by a Community Advisory Board. Impact will be evaluated via a multiple methods design using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) Qualitative Evaluation for Systematic Translation (QuEST) framework six months after program start. Quantitative data will be analyzed using descriptive statistics and standard tests of association. Data collected via semi-structured interviews with participants and program implementers will be audio-recorded, transcribed, double-coded, and analyzed via thematic analysis. Enrollment started December of 2022. 15 participants patients enrolled during two community events. Clinical trial information: NCT05694559 .

Spectrum of germline pathogenic variants among patients with cancer in Mexico.

10620 Background: Up to 10% of patients with cancer harbor pathogenic germline variants (PVs) in one or more cancer susceptibility genes. Genetic cancer risk assessment (GCRA) is an important tool for the management of patients with cancer. It allows the identification of candidates for structured screening protocols, risk reduction strategies, targeted therapies and cascade testing. Knowledge about the prevalence and spectrum of PVs is limited among underrepresented populations. We studied the prevalence of germline PVs in a cohort of Mexican patients with cancer. Methods: Between April 2017 and September 2022, patients with diagnosis of cancer who met clinical criteria for GCRA according to international guidelines (NCCN) and were enrolled in the international Clinical Cancer Genomics Community Research Network (CCGCRN) registry at Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran were included. Cancer risk counseling and germline multi-gene panel testing were performed. Post-test counseling and cascade testing with known PV analysis was offered. Results: 1322 patients met inclusion criteria (probands n = 1027, relatives n = 295). Among the probands, 72.4% (744/1027) were women, median age at cancer diagnosis was 48.2 years (range 1-88) and 9.8% (n = 101) had more than one primary tumor. 14.5% (149/1027) of probands had a positive result in which 152 PV were identified ( BRCA1 n = 39, BRCA2 n = 33, ATM n = 11, CHEK2 n = 11, MLH1 n = 11, TP53 n = 7, PALB2 n = 7, NF1 n = 6, MSH2 n = 5, MSH6 n = 3, PTEN n = 3, APC n = 2, BRIP1 n = 2, CDH1 n = 2, RB1 n = 2 and 1 PV in the genes: CDKN2A, MAX, MUTYH, NBN, PTCH1, RAD50, SDHA and SDHB). The frequency of PV according to cancer diagnosis was: breast 15.5% (82/527), prostate 2% (4/198), ovarian 15.6% (12/77), colorectal 26.6% (16/60) and pancreatic 11.9% (5/42). The frequency of recurrent, potentially founder PVs in their respective genes was as follows: BRCA1 del(exons9-12) 30.7% (12/39) and CHEK2 c.707T &gt; C 81.8% (9/11). Among the relatives referred for cascade testing the frequency of PV was 40% (118/295), 18.6% (55/295) had personal history of cancer with a median age at diagnosis of 47 years. Conclusions: Our results show a wide spectrum and a variable frequency of PVs among one of the largest examined cohorts of Mexican patients with cancer, with a high frequency of PVs among cases of breast, ovarian, and colorectal cancer. In contrast to reports from other populations, there was very low frequency of PVs among patients with prostate cancer. The outcomes of this study add to our understanding of the genetic epidemiology of cancer in the Mexican population, and support creating GCRA programs to improve access to multi-gene panel testing among underrepresented patients in limited resource settings.

Digital cancer genetic risk assessment in a gynecologic oncology clinic.

10612 Background: Population-based screening for hereditary cancer syndromes and referral of those who screen positive for genetic testing is a cost effective, evidence-based national health priority. However, under-recognition of hereditary cancer syndromes remains a critical concern, with fewer than 20% of individuals with Hereditary Breast and Ovarian Cancer Syndrome and Lynch Syndrome identified. Here, we evaluate the Ambry Genetics Comprehensive, Assessment, Risk, and Education (CARE) Program, a risk-stratification tool to assess eligibility for National Comprehensive Cancer Network (NCCN) genetic testing criteria and lifetime risk for breast cancer based on the Tyrer-Cuzick (version 8.0) risk algorithm. Methods: Between November 2022 and February 2023, new patients in a gynecologic oncology clinic were prompted by text message to complete CARE prior to their appointment. Those using CARE then completed a System Usability Scale (SUS), a validated 10-item questionnaire for the assessment of perceived usability. Results: Sixty patients presented for a new patient gynecologic oncology appointment and were prompted to complete CARE. The median patient age was 55 years (interquartile range, 40-68). The patients self-identified as Non-Hispanic White (44, 73%), Non-Hispanic Black (5, 8%), Asian (5, 8%), Hispanic (3, 5%), other (2, 3%), and unknown (1, 2%). All identified as female. Forty-three patients (72%) completed CARE. Among CARE users, 11 (26%) were identified as meeting criteria for genetic testing; of these, 9 (82%) proceeded with point-of-care same day genetic testing. Nine (21%) patients were eligible for enhanced breast cancer screening based on an estimated lifetime breast cancer risk of 20% or greater; of these, 100% were referred for high-risk breast screening. There were no patient demographics associated with completion of CARE. Forty-one patients (72%) completed the SUS survey; the median SUS score was 80 (interquartile range, 60-92.5), which corresponded to 85-89th percentile and a letter grade of A-. Conclusions: Implementation of a digital tool for cancer genetic risk assessment identified a quarter of patients to be eligible for genetic testing, among whom 82% completed same-day genetic testing. Additionally, the tool was reviewed favorably by patient users. Large randomized controlled trials of health information technology tools are needed to move closer to the goal of population-based hereditary cancer risk assessment.

A randomized controlled trial evaluating pretest cancer genetics educational video or in-person genetic counseling.

10597 Background: Cancer genetic testing indications are rapidly expanding to determine treatment eligibility for patients with cancer, to identify individual cancer risk as well as to select family members at higher cancer risk when a pathogenic variant (PV) has been identified in the family. Currently, international guidelines recommend that all candidates for genetic testing should have genetic counseling to make an informed decision for genetic testing. However, with the increased demand for genetic testing, innovative ways to deliver pretest information are needed, especially in limited resource settings, where genetic cancer professionals’ availability is scarce. Methods: This is a non-inferiority trial comparing a pretest educational video to in-person genetic counseling. Participants referred for genetic cancer risk assessment at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City were enrolled if they met international cancer genetic testing criteria and did not previously have genetic testing and/or counseling. The primary outcome was the uptake of genetic testing. Secondary outcomes included changes in genetic cancer knowledge, anxiety, and satisfaction using validated tools. Results: A total of 250 participants were included: 124 were randomized to the in-person genetic counseling arm and 126 to the educational video arm. Mean age was 47.9 years (SD 12.7), 86.4% were women, 37.2% had high-school or less and 86.4% had personal history of cancer (70% breast cancer). Overall, test acceptance was 100% in both arms. Cancer genetics knowledge improved in both groups: in-person from. 53 to .74 (diff .20; 95%CI .24-.26; p &lt; 0.05) and video from .51 to .68 (diff .16; 95%CI .20-.12; p &lt; 0.05). However, the in-person arm had a higher post counseling knowledge score (p 0.001). 43.5% and 42% of participants in the in-person and video arms had moderate-severe baseline anxiety. After intervention, both groups had a decrease in anxiety score: in-person from 5.2 to 4.7 (diff .58; 95% CI .09-1.08; p 0.01) and video from 4.9 to 4.1 (diff .75; 95%CI 0.42-1.08; p &lt; 0.05). Both groups were satisfied with genetic services (97.5% and 92.5%, respectively; p 0.34). Conclusions: A pretest educational video was non-inferior regarding genetic testing acceptance. It was also associated with improved genetic cancer knowledge and decreased anxiety levels. These results support the use of educational videos before genetic testing where in-person genetic counseling availability is limited. Clinical trial information: pending .

Evaluating cancer genetic services in a safety net system: overcoming barriers for a lasting impact beyond the CHARM research project

Underserved patients face substantial barriers to receiving cancer genetic services. The Cancer Health Assessments Reaching Many (CHARM) study evaluated ways to increase access to genetic testing for individuals in underserved populations at risk for hereditary cancer syndromes (HCS). Here, we report the successful implementation of CHARM in a low-resource environment and the development of sustainable processes to continue genetic risk assessment in this setting. The research team involved key clinical personnel and patient advisors at Denver Health to provide input on study methods and materials. Through iterative and collaborative stakeholder engagement, the team identified barriers and developed solutions that would both facilitate participation in CHARM and be feasible to implement and sustain long term in clinical care. With a focus on infrastructure building, educational modules were developed to increase awareness among referring providers, and standard methods of identifying and managing HCS patients were implemented in the electronic medical record. Three hundred sixty-four DH patients successfully completed the risk assessment tool within the study, and we observed a sustained increase in referrals to genetics for HCS (from 179 in 2017 to 427 in 2021 post-intervention). Implementation of the CHARM study at a low-resourced safety net health system resulted in sustainable improvements in access to cancer genetic risk assessment and services that continue even after the study ended.Trial registration NCT03426878

Abstract P2-05-02: Potential Empowerment and risk of Genetic Counseling with Genetic Breast cancer risk assessment in Personalized Health Care: Prospective Cohort Study using Genetic Counseling Outcome Scale (GCOS-24)

Abstract [Introduction] Personalized health care is recommended for the prevention and early detection of breast cancer. Advances in technology have made it possible to estimate genetic risk, PGV (pathogenic/likely-pathogenic germline variant) or PRS (polygenic risk score), in practice. However, linkage after risk assessment to personalized health care is still developing. One of the issues is how to tell the result especially in case of newly diagnosed PGV after Genetic Panel Testing or PRS. In this study, we evaluated genetic counseling (GC) using an established patient-reported outcome measure for clinical genetics services scale (Genetic Counseling Outcome Scale24 (GCOS24)) at genetic counseling for disclosure the results of the previous study, and examined the association with management after GC. [Method] We performed targeted sequencing for 11 breast cancer-related genes using peripheral blood DNA from 1995 female breast cancer patients. Of 1995 cases, 101 patients were PGV carriers, who were candidates of this study. Participants were referred to the Clinical Genetics unit, Kyoto University Hospital from 10 institutions (January 2018-March 2022). GCOS24 and relating questionaries were asked before and after GC. GCOS24 is a scale consisting of 24 items that assess five factors: decision control, cognitive control, behavioral control, emotional regulation, and hope. (In light of the current status of hereditary breast cancer care in Japan, 23 items were used.) Each item is rated on a scale of 1-7 points, for a total score of 23-161. In addition, we reviewed medical records to evaluate the post-GC management. [Results] Of the 101 cases, 38 cases were enrolled. The reasons of 63 not-enrolled cases were: 30 cases without follow-up (deaths or transfer to another hospital), 11 cases already diagnosed in clinical practice, 18 cases that did not wish to know their results, and 4 cases whose hospital were developing for hereditary breast cancer care. Median age at the time of genetic GC was 55 (min-max 30-83) years. Details of PGV cases were: BRCA2 23 cases, BRCA1 2, PALB2 4, PTEN 3, TP53 3, ATM 1, CHEK2 1 and NF1 1. GCOS24 after GC were improved than before GC. (Average 99 (min-max 17-124) vs 114 (91-138), Mean difference 23.9, 95% Confidence intervals (CI) 29.6 to 18.3). Thirty patients (79%) had higher increase in scores than 10.3, which was the previously reported Minimum Clinically Important Difference (MCID) of this scale. In all items except 4 items (#6,11,13,21), GCOS24 after GC were significantly improved than before GC. In post-GC management, 8 patients received or planned RRSO (risk reducing salpingo-oophorectomy) among 25 BRCA1/2 cases. There was a case with dysplastic cells detected in the resected ovary. After GC, average of GCOS24 in RRSO cases was 120 (95% CI 110 to 129), while average of GCOS24 of other BRCA1/2 cases was 110 (95% CI 104 to 116). On the other hand, two patients stopped visiting to the hospital because of fear after GC. Average of GCOS24 of 15 junior-high/high school graduate cases were 111 (95% CI 105 to 117), while average of GCOS24 of 23 college graduate cases were 117 (95% CI 111 to 122). [Discussion] In patients diagnosed with hereditary breast cancer by genetic panel testing, GC worked well except for 4 items. These 4 items (#6,11,13,21) were related to emotion. This study revealed there was also a risk to reject surveillance due to fear, suggesting that it is necessary to provide psychological support in some cases. Although the limitation of this study is the small number of cases, GCOS24 were high in RRSO cases, suggesting that GC played an important role when proceeding with intervention. We believe that the findings are helpful for the future implementation of genetic panel testing or PRS testing in healthy subjects for personalized health care. Citation Format: Nobuko Kawaguchi-Sakita, Noriko Senda, Yukiko Inagaki-Kawata, Hiromi Murakami, Sayaka Honda, Takahiro Yamada, Yuki Kataoka, Shoko Takahara, Shigeru Tsuyuki, Kazuhiko Yamagami, Yoshio Moriguchi, Masae Torii, Tatsushi Kato, Hirofumi Suwa, Wakako Tsuji, Eiji Suzuki, Akira Yamauchi, Ryuji Okamura, Shinji Kosugi, Masakazu Toi. Potential Empowerment and risk of Genetic Counseling with Genetic Breast cancer risk assessment in Personalized Health Care: Prospective Cohort Study using Genetic Counseling Outcome Scale (GCOS-24) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-05-02.

Abstract P6-02-05: Prevalence of non-BRCA germline pathogenic variants in Mexican women with breast cancer referred for genetic cancer risk assessment

Abstract Background: The prevalence of germline pathogenic variants in Mexican women with breast cancer who met the reference criteria for genetic cancer risk assessment (GCRA) has been previously reported as close to 20%. However, information regarding the spectrum of gPVs in genes other than BRCA in this population is limited. Methods: This prospective study included Mexican women who were diagnosed with BC and met international criteria for GCRA. Participants were enrolled in the Clinical Cancer Genomics Community Research Network (CCGCRN) registry and at two referral breast cancer centers in Mexico, the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City and at the Hospital Zambrano Hellion TecSalud, Monterrey. Participants underwent multigene panel testing (MGPT) for 37 cancer susceptibility genes. For this analysis, only the results of pathogenic and likely pathogenic variants in the index cases were reported. The demographic and molecular characteristics of the variants are described here. Results: From August 2017 to September 2021, 1020 Mexican women with BC underwent MGPT, with a median age at diagnosis of 41 y (range 20-86), of whom 206 (20.2%) were carriers. 208 gPVs were identified with BRCA1/2 representing 70% (145/208) of the gPVs (BRCA1 n=89, BRCA2 n=56). 63 (30%) of gPVs were identified in genes other than BRCA (CHEK2 n=21, PALB2 n=13, TP53 n=7, RAD51C n=5, ATM n=4, NF1 n=3, PTEN n=2, MUTYH homozygous n=2, RAD50 n=1, BRIP1 n=1, CDH1 n=1, NBN n=1, MSH2 n=1 and MSH6 n=1). The recurrent variants previously proposed as founders in the Hispanic population were frequent among those identified in their respective genes: CHEK2 c.707T&amp;gt;C 81% (17/21), PALB2 c.2167_2168delAT 46% (6/13) and BRCA1 del(exons 9-12) 18% (16/89). As a group, the 4 most frequent genes where gPVs were identified (BRCA1, BRCA2, CHEK2 and PALB2) represented 86% (179/208) of the positive results. Conclusion: Among the variants identified in this population of Mexican women with BC, the proportion of gPVs in genes other than BRCA was significant (about 1 out of 3 pts), which justifies the use of MGPT in the assessment of our population. However, a tailored panel (sequencing of BRCA1/BRCA2/CHEK2/PALB2 and MLPA for BRCA1) could be proposed in areas of Mexico with limited medical resources, including the analysis of other genes in selected patients according to clinical suspicion and family history of cancer. Citation Format: Yanin Chavarri-Guerra, Cynthia Villareal Garza, Jose Luis Rodriguez-Olivares, Dione Aguilar-y Mendez, Gregorio Quintero-Beulo, Francisco Gutierrez-Delgado, Josef Herzog, Stephen Gruber. Prevalence of non-BRCA germline pathogenic variants in Mexican women with breast cancer referred for genetic cancer risk assessment [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-02-05.

Improving Uptake of Cancer Genetic Risk Assessment in a Remote Tailored Risk Communication and Navigation Intervention: Large Effect Size but Room to Grow.

Cancer genetic risk assessment (CGRA) is recommended for women with ovarian cancer or high-risk breast cancer, yet fewer than 30% receive recommended genetic services, with the lowest rates among underserved populations. We hypothesized that compared with usual care (UC) and mailed targeted print (TP) education, CGRA uptake would be highest among women receiving a phone-based tailored risk counseling and navigation intervention (TCN). In this three-arm randomized trial, women with ovarian or high-risk breast cancer were recruited from statewide cancer registries in Colorado, New Jersey, and New Mexico. Participants assigned to TP received a mailed educational brochure. Participants assigned to TCN received the mailed educational brochure, an initial phone-based psychoeducational session with a health coach, a follow-up letter, and a follow-up navigation phone call. Participants' average age was 61 years, 25.4% identified as Hispanic, 5.9% identified as non-Hispanic Black, and 17.5% lived in rural areas. At 6 months, more women in TCN received CGRA (18.7%) than those in TP (3%; odds ratio, 7.4; 95% CI, 3.0 to 18.3; P < .0001) or UC (2.5%; odds ratio, 8.9; 95% CI, 3.4 to 23.5; P < .0001). There were no significant differences in CGRA uptake between TP and UC. Commonly cited barriers to genetic counseling were lack of provider referral (33.7%) and cost (26.5%), whereas anticipated difficulty coping with test results (14.0%) and cost (41.2%) were barriers for genetic testing. TCN increased CGRA uptake in a group of geographically and ethnically diverse high-risk breast and ovarian cancer survivors. Remote personalized interventions that incorporate evidence-based health communication and behavior change strategies may increase CGRA among women recruited from statewide cancer registries.

Implementing digital systems to facilitate genetic testing for hereditary cancer syndromes: An observational study of 4 clinical workflows

PurposeNational efforts have prioritized the identification of effective methods for increasing case ascertainment and delivery of evidence-based health care for individuals at elevated risk for hereditary cancers. MethodsThis study examined the uptake of genetic counseling and testing following the use of a digital cancer genetic risk assessment program implemented at 27 health care sites in 10 states using 1 of 4 clinical workflows: (1) traditional referral, (2) point-of-care scheduling, (3) point-of-care counseling/telegenetics, and (4) point-of-care testing. ResultsIn 2019, 102,542 patients were screened and 33,113 (32%) were identified as at high risk and meeting National Comprehensive Cancer Network genetic testing criteria for hereditary breast and ovarian cancer, Lynch syndrome, or both. Among those identified at high risk, 5147 (16%) proceeded with genetic testing. Genetic counseling uptake was 11% among the sites with workflows that included seeing a genetic counselor before testing, with 88% of patients proceeding with genetic testing after counseling. Uptake of genetic testing across sites varied significantly by clinical workflow (6% referral, 10% point-of-care scheduling, 14% point-of-care counseling/telegenetics, and 35% point-of-care testing, P < .0001). ConclusionStudy findings highlight the potential heterogeneity of effectiveness attributable to different care delivery approaches for implementing digital hereditary cancer risk screening programs.