Genetic Cancer Risk Assessment Research Articles

Uptake of Risk-Reducing Surgeries in an International Real-World Cohort of Hispanic Women.

Women with pathogenic variants (PVs) in breast cancer (BC) and ovarian cancer (OC) associated genes are candidates for cancer risk-reducing strategies. Limited information is available regarding risk-reducing surgeries (RRS) among Hispanics. The aim of this study was to describe the uptake of RRS in an international real-world experience of Hispanic women referred for genetic cancer risk assessment (GCRA) and to identify factors affecting uptake. Between July 1997 and December 2019, Hispanic women, living in the United States or in Latin America, enrolled in the Clinical Cancer Genomics Community Research Network registry were prospectively included. Demographic characteristics and data regarding RRS were obtained from chart reviews and patient-reported follow-up questionnaires. Median follow-up was 41 months. Among 1,736 Hispanic women referred for GCRA, 27.2% women underwent risk-reducing mastectomy (RRM), 25.5% risk-reducing salpingo-oophorectomy (RRSO) and, 10.7% both surgeries. Among BRCA carriers, rates of RRM and RRSO were 47.6% and 56.7%, respectively. In the multivariate analyses, being a carrier of a BC susceptibility gene (odds ratio [OR], 3.44), personal history of BC (OR, 6.22), living in the US (OR, 3.90), age ≤50 years (OR, 1.68) and, family history of BC (OR, 1.56) were associated with a higher likelihood of undergoing RRM. Carrying an OC susceptibility gene (OR, 6.72) was associated with a higher likelihood of undergoing RRSO. The rate of RRS among Hispanic women is suboptimal. PV carriers, women with personal history of cancer, and those with a family history of cancer were more likely to have RRS, with less uptake outside the US. Understanding personal and systemic factors influencing uptake may enable interventions to increase risk appropriate uptake of RRS.

Abstract B115: Intensive Course in genetic cancer risk assessment: Empowering clinicians, expanding clinical knowledge, and elevating care in underserved populations

Abstract Background: Despite efforts to integrate genetic cancer risk assessment (GCRA) services into mainstream medicine, the dearth of healthcare providers adequately trained in clinical cancer genetics remains a significant barrier to care, particularly in underserved communities. Since 2001, City of Hope has helped address this need through a distance mediated lntensive Course (IC) and Clinical Cancer Genomics Community of Practice (CCGCoP), with a focus on training and supporting clinicians who deliver care to underserved patient populations. Here we report on the reach, education, and practice outcomes from the past five annual cohorts of the IC in its pursuit to expand GCRA care to underserved areas and minority populations. Methods: Practice catchment area and patient population data were collected on the course application. Cancer genetics knowledge was assessed at baseline and immediate post-course; professional self-efficacy and practice changes were measured at baseline, immediate, and 12 months post-course. Results: Of 762 participants from five IC cohorts (2020-2024), 566 (74%) indicated they provide all or part of their care in an underserved area and/or to minority populations; 55 (10%) practice outside the U.S. Of these 566 clinicians, mean pre-to-post course knowledge scores increased 59%, and mean pre-to-post self-efficacy scores increased by 38%. Of 195 participants who completed a one-year post-course practice survey, 68 (35%) did not practice GCRA at baseline, of whom 61 (88%) reported implementing GCRA into their practice one-year post-course. Of 126 participants who were practicing GCRA at baseline, 55 (44%) reported an increase in their GCRA patient volume at one-year post-course. Open-ended feedback revealed that participants highly valued IC training and ongoing CCGCoP support for building and sustaining their GCRA skills, resources, and practices. Conclusions:Results demonstrate the efficacy of distance-mediated training and ongoing practice support in enhancing clinician competencies and knowledge of practicing GCRA therefore increasing access to GCRA services for underserved and minority patient populations. Efforts are underway to leverage the resources of the IC and CCGCoP to develop a more flexible, cost-effective course model and collaborate with champions to increase access to best practices in GCRA in diverse underserved settings across the US and internationally. Citation Format: Dev Tanna, John Luna, Alex Capasso, Kathleen Blazer. Intensive Course in genetic cancer risk assessment: Empowering clinicians, expanding clinical knowledge, and elevating care in underserved populations [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B115.

Prevalence and spectrum of germline pathogenic variants in cancer susceptibility genes among mexican patients with exocrine pancreatic cancer

BackgroundAlthough universal germline genetic testing is recommended for patients with exocrine pancreatic cancer (PC), access to genetic testing remains limited in low- and middle-income countries. This study aims to narrow the gap in our understanding of the spectrum of germline pathogenic and likely pathogenic variants (PVs) in cancer susceptibility genes in the Mexican population. MethodsThe landscape of PVs in cancer susceptibility genes was identified by next-generation sequencing multigene panel assays among patients with PC who were enrolled in the Clinical Cancer Genomics Community Research Network prospective registry in Mexico City. ResultsFrom August 2019 to April 2023, 137 patients underwent genetic testing. The median age at diagnosis was 60 years (range 36–85), 58.4 % were women, and 38.7 % were metastatic at diagnosis. The frequency of germline PVs was 16 % (n = 22): ATM 36.4 % (n = 8), CDKN2A/p16INK4A 27.3 % (n = 6), BRCA2 9.1 % (n = 2), PALB2 9.1 % (n = 2), CHEK2 9.1 % (n = 2), TP53 4.5 % (n = 1), and NF1 4.5 % (n = 1). Additionally, 2 carriers of monoallelic germline variants in MUTYH were identified. No significant differences were observed between carriers and non-carriers in terms of family history of pancreatic cancer. ConclusionsWe identified a significant frequency of actionable germline PVs in Mexicans with PC, wherein the majority were in a broad spectrum of genes associated with the homologous recombination DNA repair mechanism. Most pancreatic cancer associated PVs were detected in non-BRCA genes, so our findings support the recommendation of multigene panel testing for genetic cancer risk assessment of Mexican individuals with PC.

Are employees ready to engage in genetic cancer risk assessment in the workplace setting?

Are employees ready to engage in genetic cancer risk assessment in the workplace setting?

Addressing the need for genetic cancer risk assessment in Mexico: From establishment of a formal program to delivery innovation and expansion

PurposeThe purpose of this manuscript is to show the process of the establishment and adaptation of an oncogenetics program in Mexico. MethodsThe oncogentics program at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán was established as a traditional in-person service and adapted to include telemedicine counseling to expand services to other hospitals and persists as a mixed counseling model with research/commercial genetic testing. ResultsA total of 2222 participants were included with a median age of 47 years and 77.6% were women; 64% and 36% were enrolled in person and by phone, respectively; 91.1% had research testing, 4.7% commercial testing, 2% complementary pharma testing, and 2.1% had more than 1 testing. Results disclosure was by phone for 49.6%, in person for 43.3%, and by videocall for 7.1% of the cases. Cascade testing proportion was similar in both groups (88%), and 14.8% probands and 40.8% family members had a positive result for a pathogenic cancer susceptibility gene variant. ConclusionOur results demonstrated that genetic cancer risk assessment is feasible in limited resources settings and provide evidence that telemedicine is effective and can be used as an alternative in real-world populations. Our model could be adapted and potentially replicated in other institutions and countries that face similar barriers for health care.

Digital innovation for cancer risk assessment allows large-scale service redevelopment of regional cancer genetics service delivery.

Family-history assessment can identify individuals above population-risk for cancer to enable targeted Screening, Prevention and Early Detection (SPED). The online patient-facing cancer Family History Questionnaire Service (cFHQS) is a digitalised, resource efficient tool for family history data capture to facilitate this. The capturing of digital data from cFHQS allows for data interrogation of patients referred to Clinical Genetics for the purposes of service improvement. Digital data from 4,044 cFHQS respondents over a three-year period was collected and interrogated with respect to the number and type of familial tumour diagnoses to enable service improvement and streamlining of referral pathways. 81% of colorectal and 71% of breast screening assessments were population- or moderate-risk. Most patients who completed cFHQS reported more than one diagnosis of cancer/tumour/polyps in their family. 2.5% of family history assessment patients had a second indication that required assessment that would have been missed if single tumour type assessment was undertaken. Implementation of an innovative, digital family history data collection pathway has allowed large scale interrogation of referral patterns and assessment outcomes to enable service development. The high volume of inappropriate referrals to Clinical Genetics for population and moderate risk patients highlighted the need for dedicated secondary care pathway provision for these patients. The use of cFHQS streamlined family history assessment allows for redistribution of resources to improve equity and access to genetic cancer risk assessment.

Mexican physicians' knowledge and attitudes towards hereditary colorectal cancer risk management.

e22552 Background: Genetic cancer risk assessment (GCRA) has become an integral component of the management of patients with colorectal cancer (CRC). Understanding clinical criteria and interpreting screening tests to identify patients who should be prioritized for genetic testing is especially critical in resource-constrained settings such as Mexico, where access to genetic testing is limited. Methods: We designed a self-applicable survey consisting of 18 items, divided into three sections: 7 on knowledge, 5 on clinical approaches, and 6 on access to genetic testing. The aim was to assess the practice patterns of Mexican physicians in contact with patients at risk for hereditary CRC. Initially, the survey was piloted among oncology fellows to refine and improve its relevance and applicability. Following adjustments, it was disseminated using a QR code at the annual meeting of the Mexican Society of Oncology (SMeO) in September 2023. Descriptive statistics were performed using frequency and proportions for categorical variables and median and range for quantitative variables. Results: A total of 78 physicians completed the survey, with a median age of 37 years (range, 27-70). Among them, 47.2% were female, 82% were medical oncologists, with a median practice duration of 6 years (range, 1- 40). 52.6% practice in cancer community centers, 83.4% were employed in public primary care settings, and 60% were affiliated to academic centers. Referral criteria for GCRA was identified correctly in 66.7% who recognized age at CRC diagnosis < 50 years, 57.7% synchronous or metachronous CRC, 50% deficient mismatch repair CRC, and 37.2% PREMM5 score of ≥2.5%. Lynch syndrome, Familial Adenomatous Polyposis (FAP), and Cowden syndrome were identified as syndromes with an increased CRC risk by 76.9%, 71.8% and 56.7% of respondents, respectively. Decision-making based on likely pathogenic and pathogenic variants was indicated by 26.9% and 69.2%, while 12.8% reported making decisions based on variants of uncertain significance (VUS). Regarding clinical approach, 74.4% inquired about a family history of cancer at the initial consultation, and 66.7% referred patients for genetic counseling. The primary obstacles to accessing GCRA were the cost of genetic testing (43.6%) and the absence of medical genetics services at their centers (39.7%). Only 23% reported the availability of cascade testing within their practice. Conclusions: The identification of patients at risk of hereditary CRC was suboptimal among Mexican physicians. A high proportion of respondents were not fully qualified to interpret correctly genetic testing results. These indicate a need for awareness and educational programs to improve providers’ knowledge on predisposition cancer syndromes.

Predictive models as a clinical decision support tool for genetic cancer risk assessment among Mexican patients at risk of hereditary colorectal cancer.

10617 Background: Hereditary cancer syndromes, including Lynch syndrome (LS) with an increased risk of colorectal cancer (CRC), have prompted the development of clinical criteria and predictive models (PM) to identify at-risk individuals. However, these criteria have been validated with limited representation from the Latino population. Several factors may influence CRC penetrance, potentially leading to variations in PM performance across populations. Given that CRC ranks as the third most prevalent cancer worldwide, the increasing incidence of early-onset disease highlights the need for expanding Genetic Cancer Risk Assessment (GCRA) services. Methods: This prospective study included Mexican patients who were diagnosed with CRC and met NCCN criteria for GCRA. Participants were enrolled at two referral centers in Mexico, the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City and at the Hospital Zambrano Hellion TecSalud, Nuevo Leon. Participants' carrier risk was estimated using the PREMM5 model. Amsterdam II and revised Bethesda criteria, immunohistochemistry (IHC) for DNA mismatch repair (MMR) proteins in tumor tissue and multigene panel testing results were reviewed. For this analysis, only pathogenic and likely pathogenic (P/LP) variants in probands were reported. Results: From April 2016 to October 2023, 194 patients were included, with a median age at diagnosis of 45.0 (range 17-82) years, and 49.5% were women. P/LP variants were identified in 37.6% (n=73). 27.5% (n=50) were carriers of P/LP variants associated with LS (29 MLH1, 13 MSH2, 6 MSH6, and 2 PMS2). 11.8% (n=23) were carriers of P/LP variants in other genes (7 APC, 4 ATM, 3 CHEK2, 2 BRCA1, 2 TP53, 2 STK11, 1 PALB2, 1 BRIP1, and 1 MUTYH). Overall, carriers of PVs were diagnosed with CRC at a younger age than non-carriers (42 vs 46 years, p=0.034). The Amsterdam II criteria proved to be accurate (Sen 55%, Spe 91%, PPV 0.69, NPV 0.85), while the Bethesda criteria (Sen 98%, Spe 18%, PPV 0.29, NPV 0.96) and IHC for MMR proteins (Sen 94%, Spe 67%, PPV 0.61, NPV 0.95) were found to be highly sensitive. The area under the ROC curve for PREMM5 was 0.82 with a mean score 28.5 (2.1 – 50) in patients with LS and 6.0 (0.9 – 50) in non-carriers. Carriers of PVs had a higher rate of multiple primary malignancies than non-carriers (41.0% vs 19.0%, p=0.0014), and self-reported family history of CRC (65.7% vs 24.8%, p<0.001). Conclusions: Our results showed the PREMM5 model and IHC for MMR proteins effectively prioritized patients eligible for germline genetic testing in resource-limited settings. The performance of PREMM5 in this Mexican cohort was similar to that reported in the validation study of this model in other populations. Considering the spectrum of identified P/LP variants, the multigene panel test should be used in the comprehensive evaluation of Mexican patients with CRC.

Leveraging real-world data from multiple institutions to assess the rate of bilateral mastectomy after cancer genetics evaluations with genetic counselors.

e22551 Background: Genetic counselors (GCs) assess patients’ risk of cancer and counsel them on cancer screening and preventative measures, based on national guidelines. Prior studies have found that adherence to guideline-based care is higher after genetic counseling. Thus care provided by GCs leads to a variety of imaging and surgical services that can both improve patient outcomes and generate revenue for health systems, which can in turn help financially support cancer genetics programs. Research that quantifies such downstream services and revenue is lacking. We aimed to address this gap by using real-world data from multiple institutions to quantify the rate of bilateral mastectomies occurring after cancer genetics evaluations performed by GCs. Methods: We studied consecutive patients from a nationwide telehealth practice who underwent genetic counseling and cancer risk assessment with a GC after having germline genetic testing. Structured data obtained from multiple care sites via health information networks and manual chart review of electronic medical records was utilized to determine whether patients had bilateral mastectomies after the GC appointment. Results: Of the 460 consecutive patients seen by a GC, 30 were advised to consider bilateral mastectomy, based on their genetic test results and national guidelines. Data was available from the health information networks for all (29/29 (100%)) of these patients who live in the United States, with a mean follow-up of 2.7 years (SD 0.23). These 29 patients had a mean age of 43.3 years (SD 15.3), were all female, and carried mutations in BRCA2 (18/29 (62%)), BRCA1 (6/29 (21%)), or PALB2 (5/30 (17%)). Clinical data was collected from 468 locations, a median of 23 unique locations per patient. At the time of the GC appointment, 7/29 (24%) had active breast cancer, 19/29 (66%) were unaffected, and 3/29 (10%) had a history of previously treated breast cancer. Two patients were diagnosed with breast cancer after the GC appointment. 15/29 (52%) patients underwent bilateral mastectomy after the GC appointment, including most patients with active breast cancer (7/9 (78%)), 8/17 (47%) unaffected patients, and none (0/3 (0%)) with a previously treated breast cancer. Among those without breast cancer, the mean time from the GC appointment to the bilateral risk-reducing mastectomy was 8.6 months (SD 4.4). Conclusions: Half of patients who had bilateral mastectomy indicated because of their genetic test results elected to have mastectomy done after discussion of this guideline-based care option with a GC. As evidenced in prior research, bilateral mastectomy markedly reduces risk of breast cancer. In addition to improved patient outcomes, the revenue a health system receives from these surgeries can also help to support cancer genetics services.

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.

Importance of genetic cancer risk assessment as a strategy to stratify risk and provide precision prevention in high-risk patients and families.

Importance of genetic cancer risk assessment as a strategy to stratify risk and provide precision prevention in high-risk patients and families.

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.