Genetic Referral Research Articles

Impact of best practice advisory on genetic counseling referrals for young endometrial cancer patients

Impact of best practice advisory on genetic counseling referrals for young endometrial cancer patients

Genetic investigation and diagnosis in adults with congenital heart disease with or without structural or neurodevelopmental comorbidity: a retrospective chart review.

Genetic evaluation is indicated for individuals with congenital heart disease (CHD), especially if extracardiac anomalies are also present. Timely recognition of genetic diagnoses can facilitate medical management and as well as provide assessment of reproductive risk. At least 20% of the pediatric population with CHD has a syndrome or genetic diagnosis. Further, at least 30% have extracardiac congenital malformations and/or neurodevelopmental differences (NDD), and this is known to increase the likelihood of a genetic/syndromic diagnosis. However, little is known regarding whether these statistics also apply to the current population of adults living with CHD, many of whom were born prior to currently available genetic testing. The primary aim of this study was to determine the prevalence of documented genetic and syndromic diagnoses in a cohort of adults with CHD followed by a dedicated adult CHD (ACHD) clinic. The secondary aims were to describe genetic testing and genetic referral patterns in this population and identify the presence of extracardiac comorbidities which are known to be indicative of an underlying genetic diagnosis in the pediatric CHD population. To answer these questions, we performed a retrospective chart review on a sample of adults with CHD (excluding those with isolated bicuspid aortic valve) seen at Cincinnati Children's Hospital in the ACHD clinic between 2010-2021. Among 233 adult CHD patients, 36 (14%) had a documented genetic or syndromic diagnosis but only 29 (13.7%) had received genetic testing, while 27 (11.6%) had received genetic referrals. Furthermore, of 170 patients without any documented genetics related care (defined as genetic testing, genetic referrals, or genetic diagnosis), 35 (20%) had at least one congenital and/or neurodevelopmental comorbidity. Factors associated with individuals having received genetics related care included younger age (<40), male sex, and presence of extracardiac comorbidities. Our results indicate important gaps in genetics-related care for adults living with CHD. The subset of our cohort with congenital and/or neurodevelopmental comorbidities who received no genetic-related care, represent a population of adults with CHD who may have unrecognized genetic diagnoses.

Defining the Need for Services for Patients at High Risk of Breast Cancer at a Safety-Net Hospital: An Approach to Narrowing the Disparities Gap.

The National Accreditation Program for Breast Cancer (NAPBC) standards were recently revised to promote breast cancer (BC) risk assessment and subsequent referral for high-risk services. This project sought to estimate the proportion of patients at high risk for BC in the authors' safety-net hospital system, gauge patient interest in high-risk services, and define resources for program development. Women presenting for breast imaging during 2 weeks in 2023 were surveyed. Thirty-five patients with a history or diagnosis of BC were excluded. The Tyrer-Cuzick (TC) model version 8 was used to calculate BC risk. High/intermediate risk was defined as a 10-year risk of 5% or more, a lifetime risk of 15% or more, or both. The criteria for genetic counseling and testing referral were based on National Comprehensive Cancer Network guidelines. A total of 257 patients had a TC risk assessment showing 14.8% (n = 38) with a 10-year BC risk of 5% or more (consideration of endocrine therapy), 6.2% (n = 16) with a lifetime BC risk of 20% or more (qualifying for annual screening MRI), and 10.5% (n = 27) with a lifetime BC risk of 15% or more (consideration of high-risk screening). The criteria for genetic counseling/testing were met by 61 (23.7%) of the 257 patients. Overall, 31.5% (n = 81) qualified for high/intermediate-risk screening, risk reduction, and/or genetic assessment/testing, 92.8% of whom were interested in referrals for additional information and care. In the authors' community, almost one third of patients undergoing breast imaging qualify for BC high-risk assessment and services. The majority of the patients expressed interest in pursuing such services. These data will be used in financial planning and resource allocation to develop a high-risk program at the authors' institution in line with NAPBC guidelines. They are hopeful that these efforts will improve oncologic outcomes and survival from BC in their community.

Genetic Testing Practices and Pathological Assessments in End Stage Heart Failure Patients Undergoing Heart Transplantation and Left Ventricular Assist Device

BackgroundGenetic cardiomyopathies (CM) are increasingly recognized as causes of end-stage heart failure (ESHF). Identification of a genetic etiology in ESHF has important prognostic and family implications. However, genetic testing practices are understudied in ESHF patients. MethodsThis single-center, retrospective study included consecutive ESHF patients who underwent heart transplantation (HT) or left ventricular assist device (LVAD) from 2018 to 2023. Data, including genetic testing and pathology reports, were collected from the electronic medical record. Analyses of demographic and clinical characteristics were stratified by genetic testing completion and presence of clinically actionable variant. Logistic regression was performed to evaluate for associations between histology findings and genetic variants. ResultsA total of 529 adult patients (mean age 57 years) were included in the study and were predominantly male (79%, 422/529) and non-white (61%, 322/529). Genetic testing was performed in 54% (196/360) of patients with either non-ischemic or mixed CM. A clinically actionable result was identified in 36% (70/196) of patients, of which, only 43% (30/70) had a genetic counselor referral. The most common genetic variants were TTN (32%, 24/75), MYBPC3 (13%, 10/75), and TTR (11%, 8/75). Clinically actionable variants were identified in patients with known heart failure precipitators, such as alcohol use. In multivariable analysis, presence of interstitial fibrosis, specifically diffuse, on pathology was significantly associated with a clinically actionable variant (aOR 2.29, 95% CI [1.08-4.86], p = 0.03). ConclusionESHF patients with non-ischemic or mixed CM undergoing advanced therapies had a low uptake of genetic services, including testing and counselors, despite a high burden of genetic disease. Pathology findings, such as interstitial fibrosis, may provide insight into genetic etiology. The underutilization of services suggests a need for implementation strategies to improve uptake.

Differential Receipt of Genetic Services Among Patients With Gynecologic Cancer and Their Relatives: A Review of Challenges to Health Equity.

Up to 14% of endometrial cancers and 23% of epithelial ovarian cancers are associated with genetic predispositions. Referral for genetic testing and counseling can significantly impact a patient's oncologic outcomes. However, significant disparities in genetic referral and testing exist within medically underserved and minority populations in the United States. These disparities in care and access to care are multifactorial, often involving patient-level, health care-level, and system-level factors. In this review, we focus on disparities in genetic testing among patients with ovarian and uterine cancer, and the missed opportunities for primary cancer prevention among their relatives.

Germline genetic testing reveals pathogenic variants in uterine serous carcinoma patients

An increase in the risk of developing uterine serous carcinoma (USC) has been observed among BRCA1 and BRCA2 germline pathogenic variant carriers in the published literature. However, routine germline genetic testing is not currently incorporated into USC management guidelines. The primary objective of this study is to define the incidence of germline pathogenic variants identified through genetic counseling referrals for USC patients at our institution. A retrospective cohort study was performed of patients diagnosed with USC at a single institution over a seven-year interval. A total of 91 patients with uterine serous carcinoma were identified. Almost half of the patients were referred to genetic counseling, and just over half of referred patients (24/43, 56%) ultimately underwent germline genetic testing. Pathogenic variants were noted in 12.5% (3/24) of the patients who were tested. Pathogenic mutations were found in BRCA1, BRCA2, and MSH6. Variants of unknown significance (VUS) were seen in 16.6% (4/24) of patients. Based on our findings, we recommend integration of germline testing into the standard management of patients with USC.

Clinical Utility of Molecular Tumor Board Review for Identification of Possible Germline Pathogenic Variants on Tumor Next-Generation Sequencing Reports.

Tumor next-generation sequencing (NGS) testing identifies possible germline pathogenic variants (PGPVs), creating a dilemma for appropriate recognition, triage, and management. The objective of this study was to determine the clinical utility of an institutional molecular tumor board (MTB) in assessing tumor NGS reports for PGPVs. Our institutional MTB reviews all NGS reports to provide treatment and further testing recommendations, including genetic counseling referral and consideration of genetic testing (GC/GT). We studied the patients reviewed by the MTB who were recommended for GC/GT to determine the frequency of referral to a GC, germline test completion, rate of pathogenic germline variants (PGVs), factors related to PGVs, and germline conversion rate (GCR). Of the 2,355 patients reviewed by the MTB during the study period, 609 (25.9%) had a recommendation for GC/GT. Of the 609 with a GC/GT recommendation, only 181 (29.7%) were referred for GC/GT by their treating physicians, and only 107 (17.6%) completed GT. Of the 107 patients completing GT, 29 (26%) had a confirmed PGV. The only factors significantly associated with PGVs were testing due to a PGPV and higher mean variant allele fraction on the tumor NGS. Only 40 patients with a GC/GT recommendation (14.3%) due to a PGPV completed GT; however, the GCR was 42.5% (n = 17/40). The MTB review of PGPV is clinically valuable, identifying PGPV in 12% of patients undergoing tumor NGS and a GCR of 42.5%. Rates of GC/GT completion were relatively low due to under-referral by treating physicians. Given the high GCR, the authors encourage institutional algorithms to help increase GC/GT rates for patients found to have PGPV following tumor NGS testing.

53410 Retrospective Review of Clinicopathological Findings of Hereditary Leiomyomatosis and Renal Cell Cancer and Evaluation of FH/2SC Staining for Genetic Referral

53410 Retrospective Review of Clinicopathological Findings of Hereditary Leiomyomatosis and Renal Cell Cancer and Evaluation of FH/2SC Staining for Genetic Referral

Genetic Testing of Breast Cancer Patients with Very Early-Onset Breast Cancer (≤30 Years) Yields a High Rate of Germline Pathogenic Variants, Mainly in the BRCA1, TP53, and BRCA2 Genes.

Early-onset breast cancer constitutes a major criterion for genetic testing referral. Nevertheless, studies focusing on breast cancer patients (≤30 years) are limited. We investigated the contribution and spectrum of known breast-cancer-associated genes in 267 Greek women with breast cancer ≤30 years while monitoring their clinicopathological characteristics and outcomes. In this cohort, a significant proportion (39.7%) carried germline pathogenic variants (PVs) distributed in 8 genes. The majority, namely 36.7%, involved BRCA1, TP53, and BRCA2. PVs in BRCA1 were the most prevalent (28.1%), followed by TP53 (4.5%) and BRCA2 (4.1%) PVs. The contribution of PVs in CHEK2, ATM, PALB2, PTEN, and RAD51C was limited to 3%. In the patient group ≤26 years, TP53 PVs were significantly higher compared to the group 26-30 years (p = 0.0023). A total of 74.8% of TP53 carriers did not report a family history of cancer. Carriers of PVs receiving neoadjuvant chemotherapy showed an improved event-free survival (p < 0.0001) compared to non-carriers. Overall, many women with early-onset breast cancer carry clinically actionable variants, mainly in the BRCA1/2 and TP53 genes. The inclusion of timely testing of TP53 in these patients provides essential information for appropriate clinical management. This is important for countries where reimbursement involves the cost of genetic analysis of BRCA1/2 only.

Hereditary Cancer Clinics Improve Adherence to NCCN Germline Testing Guidelines for Pancreatic Cancer.

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

Genetic counseling and genetic testing for pathogenic germline mutations among high-risk patients previously diagnosed with breast cancer: a traceback approach

Genetic counseling and testing are more accessible than ever due to reduced costs, expanding indications and public awareness. Nonetheless, many patients missed the opportunity of genetic counseling and testing due to barriers that existed at that time of their cancer diagnoses. Given the identified implications of pathogenic mutations on patients’ treatment and familial outcomes, an opportunity exists to utilize a ‘traceback’ approach to retrospectively examine their genetic makeup and provide consequent insights to their disease and treatment. In this study, we identified living patients diagnosed with breast cancer (BC) between July 2007 and January 2022 who would have been eligible for testing, but not tested. Overall, 422 patients met the eligibility criteria, 282 were reached and invited to participate, and germline testing was performed for 238, accounting for 84.4% of those invited. The median age (range) was 39.5 (24–64) years at BC diagnosis and 49 (31–75) years at the date of testing. Genetic testing revealed that 25 (10.5%) patients had pathogenic/likely pathogenic (P/LP) variants; mostly in BRCA2 and BRCA1. We concluded that long overdue genetic referral through a traceback approach is feasible and effective to diagnose P/LP variants in patients with history of BC who had missed the opportunity of genetic testing, with potential clinical implications for patients and their relatives.

Quality improvement initiative leveraging tumor sequencing results to increase genetics referrals.

e23247 Background: Tumor sequencing can incidentally detect potential germline findings. Some laboratories include notifications on tumor sequencing reports about potential germline findings, but it is unknown how often these findings are acted on. It has been previously documented that these notices can help identify patients with hereditary cancer syndromes who may not otherwise undergo germline analysis due to a lack of personal/family history (phx/fhx) indication for genetics referral. After noting low numbers of referrals for patients with potential germline findings identified via tumor sequencing, we implemented an initiative to improve recognition of these findings as an indication for germline testing. Methods: Tumor sequencing reports for patients tested through two laboratories that include notifications of potential germline findings were reviewed. To assess germline referral rates for this indication, we identified patients with a potential germline finding noted on their report who did not have a prior referral for germline testing. Data were abstracted from laboratory portals and the electronic medical record (EMR). The initiative was developed by individuals with expertise in genetics, oncology, and quality improvement, and consisted of educational presentations at tumor boards and written resources. We compared referral rates in this patient population pre-initiative (PreI) and post-initiative (PostI) using Fisher Exact test. Data for the PreI patient cohort were from a pilot study of 4 clinics (5/2022-8/2022) while PostI data included all oncology clinics (2/2023-1/2024). Results: In the PreI cohort, 0/2 (0%) patients with a potential germline finding identified (and no other phx/fhx indication for referral) were referred for germline testing. Potential germline findings in the PreI cohort were not noted by the clinical team in the EMR. PostI, 11 patients undergoing tumor sequencing had a potential germline finding identified with no prior genetics referral; 5 were referred for germline testing and for 2 the finding was documented in the EMR, but the patient declined referral. In total, this was identified as an indication for referral in 7/11 (63.6%) patients PostI (p = 0.20). Conclusions: Tumor sequencing offers an opportunity to identify patients with hereditary cancer risk who may not meet classic phx/fhx criteria for germline testing. An initiative at our center was implemented to assist oncology providers in recognizing these referrals. While there was improvement in referral rates after the initiative, this was not significantly different, likely due to the small sample size. Analysis of our PostI cohort indications also showed that these potential germline findings are still not being consistently recognized by oncology providers, indicating a different or multi-pronged approach to identify patients with this indication for germline referral may be needed.

Improved germline screening for patients with pancreatic cancer through provider driven testing.

e16366 Background: National guidelines recommend germline genetic screening for all pancreatic cancer patients. Results provide meaningful insights into pathogenic variants and impacts both treatment selection and family screening recommendations. We previously reported on current state and the need to improve germline screening rates. Since implementing a provider-driven approach, we have seen a significant increase in testing. Our findings demonstrate the feasibility and ongoing need for novel approaches to germline screening. Methods: This is a retrospective review of 223 patients with pancreatic adenocarcinoma evaluated at the University of Virginia Health System within the calendar year of 2022 compared to the 2021 calendar year. Primary endpoints include the rate of genetic counseling referral placement, the rate of attendance of outpatient genetic counseling, and the rate of individuals who completed germline screening. Our primary data points will be compared with outcomes obtained from a prior study evaluating 210 patients with pancreatic adenocarcinoma in the calendar year of 2021 at the same academic medical center. Results: Of the 223 patients with pancreatic adenocarcinoma, only 30% (69/223) had genetic counseling referrals present in the electronic health record system (EHR). This was an improvement from the 2021 calendar year, where 19% (39/210) had referrals present in the EHR. Of those with referrals present, an improvement in the rate of genetic counseling attendance was found, from 51% (20/39) in 2021 to 58% (40/69) in 2022. There was also an improvement in the rate of germline screening completion rates; 38% (85/223) of patients evaluated in 2022 completed testing, compared to 21% (44/210) in 2021. Six percent (5/85) of tested patients in 2022 had pathogenic findings, consistent with historical incidence rates. The main provider barriers were time and testing logistics. Conclusions: Our data shows an improvement in the rates of genetic counseling referrals, the rates of genetic counseling attendance, and the rates of germline screening completion. This modest improvement is primarily related to increased awareness by our providers. We acknowledge the need for further improvements and are developing a prospective clinical trial to better educate and empower patients to understand the need and results of germline testing.

Implementation of universal germline testing in underserved patients with young onset gastrointestinal cancer.

10602 Background: Universal germline testing (UGT) in solid cancer patients increases the detection of pathogenic germline variants (PGVs) over guideline-based testing. There is a rising incidence of young onset (YO) gastrointestinal (GI) cancers (50 years and under). PGV rates in this population can be as high as 20%, highlighting the benefit of UGT. Underserved populations experience significant disparities in germline testing. The primary aim of this study is to evaluate rates of germline testing among patients with young onset (YO) GI cancers in a large safety net population and identify barriers and facilitators of testing in order to improve the process. Methods: In this retrospective study, we identified 202 patients ages 18-50 diagnosed with GI cancers between January 2019 and December 2022 at the Lyndon B. Johnson Hospital. Demographic and clinical data were collected and the rate, outcome and process of standard of care germline testing evaluated. Paired T-tests were used to identify factors associated with timeliness and completion of germline. Results: The majority of patients had colorectal (68%) followed by gastro-esophageal cancers (16%). Median age at diagnosis was 42 years. One third were diagnosed with stage IV disease. Half of all patients were recipients of financial assistance based on household income less than 150% of the Federal Poverty Level. Spanish was the primary language spoken by 58% of patients. Among all patients, 148 (73%) were referred to a genetics counselor with germline testing offered in 111 (55%) and completed in 99 (49%). PGVs were identified in 17% of patients tested while variants of uncertain significance were found in 19%. Patients with colon cancer (p&lt;0.001), microsatellite instability on immunohistochemistry (p&lt;0.001), and those with a first-degree relative with cancer (p&lt;0.001) were more likely to complete genetic testing. The average time from initial oncology visit to genetics referral was 20 weeks while that from referral to genetics appointment was 22.5 weeks. The average time from genetics appointment to completion of testing was 14.5 weeks. Patients with private insurance had a significantly shorter time to genetics referral (p&lt;0.05) while English-speakers had a longer time from referral to initial genetics appointment (p 0.019) and to completion of testing (p 0.044). Uninsured patients had significantly lengthier times to test completion (p 0.013). Conclusions: PGVs were detected in 17% of patients with YO GI cancers. Along the genetics services care delivery continuum, patient selection for genetic counselor referral, uptake of genetic testing and timeliness of testing were identified as key barriers to germline testing. Given the high detection rate and barriers to testing identified in this underserved population, we have designed a multilevel intervention aimed at optimizing the implementation of UGT in patients with YO GI cancers.

Pathogenic germline variant discovery in plasma cell disorders: Insights from genetic counseling referrals and testing.

10619 Background: Our research has shown that 10% of multiple myeloma (MM) patients harbor pathogenic or likely-pathogenic germline variants (PGVs) in cancer predisposition genes, with a significant enrichment observed in BRCA1/2 genes. PGVs are notably more common in younger MM patients and those with a personal or familial cancer history. This study presents our experience in referring plasma cell disorder (PCD) patients at increased risk for carrying PGVs, due to either clinical history or suspicious tumor NGS findings, for genetic counseling and subsequent germline testing. Methods: This retrospective study reviewed patient records from our institution's PCD clinic, focusing on those referred for a genetic evaluation between 2020 and 2024 due to suspected cancer predisposition. We compiled demographic and clinical data for these patients, reasons for referral, and cancer history of patients and their families. The uptake of germline testing, identified mutations, and subsequent recommendations for advanced cancer surveillance and prevention, including cascade testing, were also analyzed. Germline testing utilized targeted hereditary cancer panels from five companies and was conducted on DNA samples extracted from peripheral blood, saliva/buccal swabs, or skin biopsies. Results: 52 PCD patients underwent a genetic evaluation and were included in this review, comprising 31 MM, 9 smoldering MM, and 12 MGUS cases. Median age at the time of referral was 63, and 54% of patients were female. Racial composition was 62% White, 15% Black/African-American, 12% Hispanic, 2% Asian, with 10% undisclosed. 8 patients were referred due to suspicious findings in tumor NGS, while the rest were referred due to clinical suspicion. A personal history of cancer was reported by 19 patients (37%), and 49 had a first- or second-degree relative with cancer (94%). 38 patients (73%) underwent germline testing, of which 15 (39%) harbored PGVs (11 had MM, 4 had smoldering MM). 8 PGV carriers had well-established founder variants. The remaining 7 had PGVs in genes including BRCA2 (n=3), PALB2 (n=1), BLM (n=1), SMAD4 (n=1) and NTHL1 (n=1). Of note, all 8 referred for suspicious findings in tumor NGS were confirmed to harbor PGVs. All PGV-positive patients were recommended for cascade testing and enhanced cancer screening. Conclusions: Our findings indicate a 39% PGV detection rate in PCD patients referred for genetic evaluation, underscoring the potential benefit of implementing screening guidelines in this population. PGV detection led to recommendations for intensified surveillance and cascade testing in all cases, impacting both patients and their families. The discovery of BRCA2PGVs in 20% (3/15) of cases reinforces its potential role as a predisposition gene in MM, corroborating our prior findings.

Timing of genetic testing referral and genetic testing results in patients with multiple primary cancers.

10592 Background: An individual diagnosed with a metachronous or synchronous cancer that arises independently, not due to recurrence or metastasis, has multiple primary cancers (MPC). Practice guidelines recommend germline genetic testing based on specific combinations of primary cancers and ages of diagnoses but do not recommend testing for all patients with MPC. In prior work (PubMed ID 37276540), we found that patients with breast cancer are more likely to receive testing than patients with other primary cancer types. Here, we evaluated whether a first breast cancer was more likely than another first cancer type to prompt testing referral. Methods: Using Oncoshare, a breast cancer research database that integrates data from electronic medical records and the California Cancer Registry, we identified female patients with MPC diagnosed between January 2000 and June 2023 with breast cancer as either the first or second cancer and seen at Stanford University. We analyzed testing rates after first vs. second cancer diagnosis and the yield of pathogenic variants (PV). We evaluated the association between the receipt of genetic testing and the timing of breast cancer (1st or 2nd), using both univariate and multivariable logistic regression that adjusted for age at first diagnosis, race/ethnicity, and time between the first and second diagnoses. Results: 1,069 patients met the study eligibility; 75% were non-Hispanic White, and 73% had breast as the first cancer. 342 (32%) patients had testing, and 113 (33%) had at least one PV. Most patients had testing after the first cancer (44%, n=150) or after the second cancer (48%, n=165) (Table). Those with breast cancer as their first primary tended to have a higher testing rate, (OR 1.62, 95% CI 0.9-3.0), however, the statistical significance of this association was attenuated in the multivariable model with more parameters (P=0.11), possibly due to small sample size. Overall PV yield (33%) was high, consistent with a tertiary referral center. Conclusions: In this academic clinic-based sample of patients with MPC, we observed a higher testing rate when breast vs. another cancer was the first primary although it did not reach statistical significance. Additional research is needed to validate this finding in a larger cohort and determine whether similar referral patterns are observed in community practice, where most U.S. patients receive cancer care. [Table: see text]

A retrospective cohort study of genetic referral and diagnosis of Birt-Hogg-Dubé Syndrome in patients with Trichodiscoma and Fibrofolliculoma skin lesions.

Birt-Hogg-Dubé (BHD) syndrome is a genetic condition caused by pathogenic variants in the FLCN gene resulting in benign skin lesions, spontaneous pneumothorax, and increased risk for a variety of renal tumors. Skin manifestations of BHD include trichodiscoma (TD) and fibrofolliculoma (FF), which may represent the same pathologic entity. These lesions can identify BHD patients, who upon positive genetic testing can be considered for life-long surveillance for renal neoplasms. To characterize patients diagnosed with TD and FF including rates and outcomes of genetics referral. Retrospective chart reviews of patients with confirmed or possible diagnosis of TD or FF at the University of Michigan from September 2002 through October 2020 to assess pathologic findings, personal and family history of BHD manifestations, referral for genetic evaluation, and genetic testing results. 64 patients had a pathologic diagnosis of TD or FF, 16 of whom (25%) were referred to cancer genetics. Fourteen patients completed genetic evaluation, 9 of whom were diagnosed with BHD (64%), with 6 unique pathogenic variants in FLCN. Providers should consider referral for genetic evaluation for patients with biopsy-proven TD or FF, as early diagnosis of BHD provides the opportunity for early detection and treatment of other BHD-associated conditions.

Risk-reducing salpingo-oophorectomy among diverse patients with BRCA mutations at an urban public hospital: a mixed methods study

ObjectivesTo assess the association of socioeconomic demographics with recommendation for and uptake of risk-reducing bilateral salpingo-oophorectomy (rrBSO) in patients with BRCA1 and BRCA2 (BRCA1/2) mutations.DesignRetrospective cohort, semistructured qualitative interviews.Setting and...

Current approach to genetic testing and genetic evaluation referrals for adults with congenital heart disease.

Congenital heart disease (CHD) is the most common congenital anomaly. Up to 33% have an identifiable genetic etiology. Improved medical and surgical management of CHD has translated into longer life expectancy and a rapidly growing population of adults living with CHD. The adult CHD (ACHD) population did not have access during childhood to the genetic technologies available today and therefore have not had a robust genetic evaluation that is currently recommended for infants with CHD. Given this potential benefit; the aims of this study were to determine how ACHD cardiologists offer genetics services to patients and identify the indications that influence decision-making for genetics care. We performed a descriptive cross-sectional study of ACHD cardiologists. A study-developed questionnaire was distributed via emailed REDCap link. The recruitment email was sent to 104 potential respondents. The survey was open from 06/2022 to 01/2023. Thirty-five cardiologists participated in the study (response rate of 34%). Most cardiologists identified as white (77%) and male (66%). Cardiologists were more likely to refer patients to genetics (91%) than to order testing themselves (57%). Of the testing ordered, chromosomal testing (55%) was ordered more than gene sequencing (14%). Most cardiologists would refer a patient with a conotruncal lesion (interrupted aortic arch) over other indications for a genetics evaluation. There were more reported barriers to ordering genetic testing (66%) compared to referring to genetics for a genetics evaluation (23%). Cardiologists were more confident recognizing features suggestive of a genetic syndrome than ordering the correct test (p = 0.001). Regarding associations between clinical factors and current practices, more years in practice trended towards less referrals and testing. Evaluating a greater number of patients (p = 0.11) and greater confidence recognizing syndromic features (p = 0.12) and ordering the correct test (p = 0.09) were all associated with ordering more testing. Testing for microdeletion syndromes is being offered and completed in the ACHD population, however testing for single-gene disorders associated with CHD is being under-utilized. Developing guidelines for genetic testing in adults with CHD could increase access to genetic services, impact medical management, reduce uncertainty regarding prognosis, and inform recurrence risk estimates.

Abstract PO1-09-06: Patient Barriers to Genetic Counseling

Abstract Patient Barriers to Genetic Counseling Background: Access to genetic counseling is becoming more important as new targeted drugs are developed and as recommendations for testing for hereditary cancer syndromes expands. Yet, significant barriers hinder patients’ access to these services leading to a certain percentage of patients declining a genetic counseling referral (Ochoa, O’Neill). Among one of the more often cited reasons for declining genetic counseling is the cost of the consultation when it is not covered by insurance or a patient is uninsured. This potentially limits patient treatment options and can result in a missed opportunity to identify at-risk relatives. There is scant data documenting why women do not accept genetic counseling referrals and our study sought to better identify these potential barriers. In doing so we hope to enable healthcare providers and policymakers to develop strategies to ensure equitable access to these crucial services. Methods: Breast cancer patients for whom a genetic counseling referral was placed and who self-declared the inability to pay our Cancer Center’s genetic counseling fee ($126) were approached about filling out an anonymous survey regarding their reasons for declining. The survey queried, in addition to cost, other patient-related barriers to genetic testing. The survey also captured the number of first-degree relatives who might be affected by an actionable pathogenic variant. After patients were consented and completed the survey, genetic testing, paid for by the study, was offered. Results: To date, 13 patients were approached about the study and 10 patients (77%) agreed to participate, were consented and filled out surveys. Women could choose more than one reason for declining a genetic counseling referral but the most prevalent reasons cited were cost (10), worried there is nothing to be done about inherited cancers (3), concern about genetic material being taken and/or results being used against them (2), too many appointments (2). Of these 10, all (100%) elected to proceed with genetic counseling and all 10 (100%) elected to proceed with genetic testing. Two of the 10 patients (20%) tested were found to have actionable pathogenic variants (one in BRCA2 and one in CHEK2) potentially impacting 13 adult first-degree relatives. Conclusion: These preliminary findings underscore the importance of access to genetic counseling in order to facilitate appropriate genetic testing. The identification of actionable genetic mutations allows for early detection, timely interventions, and tailored management plans, ultimately leading to improved patient outcomes. By identifying cost as the most often cited reason for declining genetic counseling, healthcare providers and policymakers can develop strategies such as the implementation of financial assistance programs and universal insurance coverage for genetic counseling services in order to alleviate the financial burden and ensure equitable access to these crucial services.