Implementing a Genetic Counselor‐Led Model for Hereditary Myeloid Malignancies: A Real‐World Study

Disparities in completion of genetic testing and counseling for Lynch syndrome in high-risk patients diagnosed with endometrial cancer (601)

10605 Background: Scalable and reliable approaches are needed to assist non-genetics clinicians in assessing whether a patient meets criteria for germline genetic testing. Insurance coverage of genetic testing often depends on such assessments. RISE Risk Assessment Module: Hereditary Cancer is a brief patient-administered digital tool designed for this purpose. The tool’s assessment is based on personal and family history and is informed by national guidelines. The aim of this study was to assess the clinical validity of this digital tool by evaluating its agreement with assessments made by genetic counselors. Methods: We performed a chart review of cases from a telehealth genetic counseling practice seen July to October 2020. Extracted history was entered into the tool by the research team to model how a patient would complete the digital tool. The tool’s assessment of whether the patient met criteria for genetic testing was compared to the assessment of the genetic counselor who saw the patient. To further validate the tool, a subset of cases were analyzed for agreement between the tool and research team on which specific history-based rules in the tool’s algorithm applied for a given case. Results: The majority (121/152; 80%) of cases were female and the mean age was 52.3 (SD 15.9). Just over half of cases (85/152; 56%) had a personal history of cancer, including breast (27/85; 32%), colon (15/85; 18%), prostate (10/85; 12%), endometrial (12/85; 14%), and ovarian (7/85; 8%). 100/152 (66%) of cases met criteria for genetic testing. In 146/152 (96%) cases there was agreement between the assessments made by the tool and the genetic counselor regarding whether the patient met criteria for germline genetic testing. Nearly all disagreement (4/6; 67%) resulted from history intentionally left out of the tool as patients can rarely report them (aspects of tumor pathology 3/4; risk of having a pathogenic variant based on predictive models 1/4). For a subset of cases (62/152) we compared the tool and research team’s assessments of which aspects of the patient’s personal and family history met criteria for genetic testing. This was done by looking at which rules in the tool’s algorithm were triggered by the patient’s history. There was complete agreement between the tool and research team on which rules should be triggered. Completion of the tool took a mean of 3.3 minutes. Conclusions: The high level of agreement between the digital tool and genetic counselors supports RISE Risk Assessment Module: Hereditary Cancer as a clinically valid method of identifying individuals in need of evaluation for hereditary cancer predisposition. Complete agreement on which history-based rules applied in these cases further supports the clinical validity of the tool. Our results also suggest that the tool’s assessment can be delivered in under 5 minutes, which is critical to feasibility and scalability of the digital tool.

Genetic Counseling and Testing for Pulmonary Arterial Hypertension in the United States

1586 Background: The U.S. Preventive Services Task Force (USPSTF) recommends that women who meet family history criteria for hereditary breast and ovarian cancer (HBOC) be referred for genetic counseling. However, HBOC genetic testing is under-utilized, particularly among racial/ethnic minorities. We evaluated different methods of family history intake, including a validated family history screener, documentation in the electronic health record (EHR), and a web-based decision aid (DA). Methods: Among women undergoing screening mammography, we administered a validated family history screener to determine eligibility for BRCA genetic testing based upon USPSTF guidelines. We developed a patient-centered DA ( RealRisks) which includes modules on breast cancer risk, collection of detailed family history, and information on HBOC genetic testing. Women who met high-risk criteria for breast cancer were enrolled in an intervention trial to determine whether exposure to RealRisks increases referrals for high-risk consultations. BRCA genetic counseling/testing uptake was assessed by self-report and EHR review. Results: From November 2014 to June 2016, 3077 women completed the family history screener. Median age was 59 years (range, 29-99), including 76% Hispanic, 4% Ashkenazi Jewish, and 60% with a high school education or less. 12% met family history criteria for BRCA genetic testing based upon the family history screener, of which only 5.9% had previously undergone genetic counseling or testing. Sixty high-risk women were enrolled to access RealRisks. When family histories based upon the screener, DA, and EHR were compared, 12 (20%) had discrepancies in number of affected relatives, type of cancer, and age at diagnosis which changed eligibility for BRCA testing. Follow-up is ongoing to determine whether the DA facilitates appropriate referrals for genetic counseling. Conclusions: In a population of predominantly Hispanic and less educated women, a large proportion met USPSTF family history criteria for BRCA testing, but uptake of genetic counseling was low. Developing decision support for accurate family history intake is critical to identifying appropriate candidates for genetic referrals.

Introduction: Approximately one out of eight women get breast cancer in their lifetime, and the National Cancer Institute estimates 268,600 new diagnoses in 2019. About 5-10% of breast cancers can be attributed to a genetic predisposition. Identifying women with genetic predispositions is significant because they qualify for more intense breast cancer screening or risk reducing strategies. Unfortunately, genetic testing is often not offered until cancer is diagnosed. This traditional genetic testing model is reactive rather than proactive, and it fails to identify a large proportion of unaffected genetic mutation carriers in the United States. Purpose: Our goal was to create a proactive system for identifying women at high risk for breast cancer. We integrated an online family history software, Progeny, into our mammography center to screen unaffected women for high-risk status (Tyrer-Cuzick (TC) score ≥ 20%) and National Comprehensive Cancer Network (NCCN) genetic testing criteria. Methods: Patients undergoing breast imaging were given a computer tablet with a preprogrammed Progeny questionnaire. Progeny collects the patient’s gynecological and family history, calculates a TC risk score, and assesses NCCN genetic testing criteria. Progeny was integrated into the mammography center on 1/10/2019 and this preliminary data was collected through 6/6/2019. Summary statistics were tabulated. Results: A total of 3,129 patients were invited to complete the questionnaire. 2,474 (79.1%) completed the questionnaire and 540 (21.8%) met NCCN genetic testing criteria. The average age of those meeting NCCN criteria was 60.3 years (range: 21-94). Of the patients who completed the questionnaire, 148 (6.0%) patients were found to be high-risk due to a TC score ≥20%. Clinical Impact: We found 540 patients who qualified for genetic counseling/testing. Under the previous, reactive genetic testing model, most of these patients would not have been selected for testing unless they received a cancer diagnosis. We recommended pretest genetic counseling to all these high-risk patients. Typical oncology genetic counselors see 10.2 new patients a week and our clinic can see 15 new patients per week. It would take 36 weeks with our current clinic system for all the patients identified during the initial questionnaire trial period to see a genetic counselor for pretest counseling. This demand alone would require two full time genetic counselors to accommodate. Conclusion: Our initial experience integrating a genetic screening questionnaire into our mammography center shows that 22% of patients need genetic testing and 6% need follow-up in a high-risk breast cancer clinic. Given current staffing constraints, it would take about 9 months to genetic test and counsel the patients identified after just 6 months of screening. This estimate does not include the demand placed on genetic counselors from current referral sources, so actual wait times could be longer than 9 months. This long wait time could increase anxiety for patients and dissatisfaction for patients and providers. A new approach to offering genetic testing and counseling to these patients is needed. Future Directions: In response to this increased clinical demand, we are partnering with Progeny and Ambry Genetics to create a novel program that allows patients to receive preliminary genetic education by video and genetic testing the same day as their mammogram appointment. Ultimately, the hope is that this new, high volume, proactive high-risk prevention program will allow a larger proportion of women with a genetic predisposition to receive diagnoses of their mutations and to initiate risk reducing and life-saving treatments. With this partnership, we will better accommodate the increased patient demand for genetic testing and avoid long wait times for counseling. Citation Format: Rebecca C Luiten, Vilert A Loving, Jennifer Siettmann, Beverly Reyes, Lida A Mina. Creation of a high volume, proactive high-risk breast cancer prevention program [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-03.

Genetic counseling and testing for hereditary cancer risk in young adult women: Facilitating autonomy and informed decision making is key

Background: Up to 18% of adult hematology patients (pts) suspected of having an inherited predisposition are found to have a germline mutation leading to a hereditary hematologic disorder (HHD). Timely identification of these disorders leads to heightened surveillance for malignancies, specific treatment regimens, donor selection, transplant conditioning regimens, cascade testing in family members and supportive care. Unlike solid tumour hereditary cancer syndromes, the investigations in HHD are more complex and there is no formal consensus of referral criteria or genetic testing criteria. We describe our initial experience in this patient population at our centre, the Princess Margaret Cancer Centre (PM). We have established a workflow to initiate germline genetic testing in pts under suspicion for a HHD. This involves a collaboration with a genetics clinic to 1) capture pts based on their personal/family history of cancer and suggestive genetic findings identified on bone marrow/blood, 2) procure a skin biopsy for fibroblast culture and germline DNA extraction and 3) provide follow-up counselling and management for positive results. Aims: Our goal is to evaluate the positivity rate of germline mutations in adult hematology pts who were referred for genetics assessment. Methods: The PM is the largest leukemia Centre in Canada, and has seen over 3000 adult pts with a malignant disorder from 2015-2021 (AML:1597, MDS:472, ALL:286, MPN:664 and marrow failure:22). We performed a retrospective chart review of all adult hematology pts referred to cancer genetics service for HHD workup during this time period. Results: 116 pts (66 male, 50 female) were suspected for a HHD and referred for germline genetic testing on fibroblast DNA. 52 pts (45%) were ≤40y old and 64 pts (55%) >40y old (age range 18-86y, median 53y). 71 pts (61%) were referred with a positive family history of hematologic disorders (HD). In addition, 61 pts presented with a myeloid malignancy (46 with MDS, AML, or CML, and 15 with a MPN), 42 presented with a lymphoid malignancy (ALL, CLL, or lymphoma), 8 presented with bone marrow failure, and 5 presented with other HD. 40 pts were found to have a germline genetic mutation, 7 of which were associated with carrier status. In total, 33 (28.4%) referred pts were found to have at least one actionable germline mutation. This corresponds to a positive genetic result found in 30% of pts referred with MDS/AML, 33% of pts referred with a lymphoid malignancy, and 18% of pts referred with bone marrow failure, MPN, or other HD. Additionally, 18 (55%) of these pts had a positive family history of HD, while 15 (45%) presented with no family history of HD. Of these 33 positive cases, 13 (11.2% of all referrals) occurred in a gene associated with a hematologic malignancy and resulted in a HHD diagnosis. 20 pts were found to have a mutation in a gene associated with a non-hematologic hereditary cancer syndrome. After the implementation of a HHD genetics workflow in 2018, we saw an increase in the total number of referrals to a genetics clinic over the past seven years, with 25 pts (6 positive cases) referred between 2015-2018, and 91 pts (27 positive cases) referred between 2019-2021. Image:Summary/Conclusion: Our overall positivity rate was 28.4% which includes mutations in any hereditary cancer gene, and 11.2% for HHDs. Our high pickup rate across all age groups and the increase in the number of referrals to genetics service suggests that more pts with HD, including older pts, would benefit from consultation with specialized centres that are experienced in the evaluation and treatment of these disorders.

Community health worker supported hereditary cancer risk assessment in a large safety net hospital (429)

10614 Background: Multiple guidelines recommend hereditary cancer risk assessment for all adults, yet it rarely is performed. This is largely due to the time-consuming nature of such assessments and difficulty with access to genetic counseling for those at high risk. We designed a care model to address these issues that is suitable for both oncology and non-oncology settings. It includes a brief patient-administered and clinically validated digital hereditary cancer risk assessment tool, followed by immediate online self-scheduling features for telehealth genetic counseling, with appointments available within 48 hours. The digital tool uses a guideline-based algorithm to assess whether genetic testing for hereditary cancer risk is indicated. Here we aim to evaluate the effectiveness and timeliness of this model. Methods: We conducted a retrospective chart review of consecutive patients that engaged with this model from May 2021 to August 2023 at 32 obstetrics and gynecology clinics. We also used nationwide data from the National Society of Genetic Counselor's (NSGC) Professional Status Survey. To assess timeliness of genetic counseling appointments in this care model, we compared the time from scheduling the appointment to the start of the appointment to wait times at health systems for comparable non-urgent cancer genetic counseling appointments, from the NSGC data. Effectiveness was assessed via rates of completion of the tool and scheduling of genetic counseling. Results: 2538 patients (98% female, mean age 37 years, 3.9% with a personal history of cancer) initiated the care model and 95% (2415/2538) completed the risk assessment tool. A quarter (26% (628/2415)) met criteria for germline genetic testing. The median time to complete the tool was 2.7 minutes (IQR 2.9). At the end of the tool, patients could click a button to schedule an appointment with a genetic counselor to discuss hereditary cancer risk and genetic testing. 44% (274/628) booked an appointment. The median time from scheduling to genetic counseling appointment was 2.8 days (IQR 4.9 days), which is shorter than the median wait time for comparable genetic counseling appointments at health systems in the nationwide NSGC dataset (21 days (IQR 53 days); p<< 0.01). Conclusions: The tool completion rate, rate of patients meeting criteria, and uptake of genetic counseling indicate the model is effective. Timeliness was improved by this model, with the digital tool assessing risk in ~3 minutes, compared to previous reports of ~30 minutes for manual hereditary cancer risk assessment. In addition, the timeliness of genetic counseling appointments was markedly better than the current standard of care. These findings suggest that this care model can support physicians in providing timely guideline-recommended hereditary cancer risk assessment to their patients.

6574 Background: Trinidad and Tobago (T&T) is the southern-most Caribbean island, and according to the WHO/PAHO, it has the 2nd highest breast cancer mortality rate in the region. Notably, a large proportion of breast cancer cases in T&T occur at a young age; with nearly 36% of them being diagnosed under the age of 50. There is a known association between a younger age at diagnosis and Hereditary Breast and Ovarian Cancer syndrome (HBOC). Yet, the prevalence of HBOC mutations remains unknown in T&T, as genetic counseling and testing services are extremely limited in the region. Therefore, we sought to determine the prevalence and spectrum of HBOC mutations in T&T. Methods: At the National Radiotherapy Center, T&T’s main oncology unit, female breast cancer patients, who met NCCN criteria for further genetic counseling and testing were recruited through chart reviews. After pre-test counseling, enrolled subjects had a detailed interview about their personal breast cancer diagnosis and family history. A saliva sample was collected using an Oragene kit, and analyzed by Color Genomics Inc. for 30 genes associated with hereditary cancers. Finalized results were returned to patients by genetic counselors from Color Genomics. Results: A total of 118 female patients who met NCCN guidelines for HBOC testing received genetic testing. A majority were 50 years of age or younger (69/118, 59%). The cohort was ethnically diverse: 34% African, 15% Asian, 48% multiple ethnicity, and 3% other/unknown. A pathogenic or likely pathogenic variant (positive result) was identified in 21.2% of the cohort (25/118) - most commonly identified in the BRCA1 gene (13/25, 52%), followed by BRCA2 (5/25, 20%), PTEN (2/25, 8%), BRIP1 (1/25, 4%), CHEK2 (1/25, 4%), MSH6 (1/25, 4%), PALB2 (1/25, 4%), and RAD51C (1/25, 4%). Conclusions: We found a strikingly high HBOC germline mutation prevalence rate of 21.2% among a cohort of female breast cancer patients meeting NCCN criteria for HBOC testing in T&T. Given the growing implications of germline HBOC mutations for breast cancer treatment and prevention, our results demonstrate an urgent need for funding, as well as the development of robust genetic counseling and testing services in T&T.

Genetic testing for Parkinson’s disease (PD) is increasing globally, and genetic counseling is an important service that provides information and promotes understanding about PD genetics and genetic testing. PD research studies have initiated outreach to underrepresented regions in North America, including regions in Latin America, such as the Dominican Republic (DR); some studies may include return of genetic test results. Thus, understanding what individuals know about PD, genetic testing for PD, and their interest in speaking with a genetic counselor, is crucial when assessing readiness. In this cross-sectional study, a survey was distributed to people with Parkinson’s disease (PwP) and their unaffected biological relatives in the DR. Questions assessed genetics knowledge, attitude toward genetic testing, and interest in genetic testing and counseling. Of 45 participants, 69% scored the maximum on the attitude scale, indicating an overall positive attitude toward genetic testing; 95% indicated interest in genetic testing for PD, and 98% were at least somewhat interested in meeting with a genetic counselor. The mean PD genetics knowledge score was similar to previously published data. Through free text responses, participants expressed a desire to know more about PD treatment and management, prevention, cause, and their personal risk for PD. These results provide further evidence of readiness for genetic testing in this country but also underscore some gaps in knowledge that should be addressed with targeted educational efforts, as part of building genetic testing and counseling capacities.

The purpose ot this study was to assess the effectiveness of an educational video compared to in-person genetic counseling for cancer genetic testing candidates. Genetic cancer risk assessment is essential for tailoring oncological treatment, identifying individuals at higher risk of cancer, implementing risk-reduction strategies, and enabling family cascade testing. Pretest genetic counseling facilitates an individual's informed decision making and reduces anxiety. However, the availability of genetics specialists is limited in constrained resource settings. We conducted a randomized controlled noninferiority clinical trial comparing an educational video (intervention arm) with in-person (control arm) genetic counseling for cancer genetic testing candidates. The main outcome was genetic testing acceptance, requiring the 95% CI around the intervention difference to be less than (-)10 percentage points to claim noninferiority. Secondary outcomes included genetic knowledge, anxiety, and satisfaction. We included 250 participants who met criteria for cancer genetic testing, with a mean age of 47.9 years (standard deviation, 12.7); 86.4% were women. All participants in both arms accepted genetic testing (difference = 0% [95% CI, -0.04% to 0%]; P = 1.0). Knowledge improved in both groups: score increments were 20 (95% CI, 16 to 24; P < .05) in the control arm and 16 (95% CI, 12 to 20; P < .05) in the intervention arm. Anxiety scores decreased: -0.58 (95% CI, -0.09 to -1.08; P = .01) in the control arm and -0.75 (95% CI, -0.42 to -0.08; P < .05) in the intervention arm. Satisfaction levels were 97.5% and 92.5%, respectively (P = .34). The educational video is noninferior to in-person genetic counseling for genetic testing acceptance, improves genetic knowledge, and reduces anxiety. These findings support using educational videos to address the shortage of genetic counseling professionals.

Despite efforts to increase the availability of clinical genetic testing and counseling for Hereditary Breast and Ovarian (HBOC)-related cancers, these services remain underutilized in clinical settings. There have been few efforts to understand the public’s use of cancer genetic services, particularly for HBOC-related cancers. This analysis is based on data from the 2015 National Health Interview Survey (NHIS), a U.S.-based nationwide probability sample, to better understand the public’s use of HBOC-related clinical cancer genetic services. Bivariate analyses were used to compute percentages and examine the associations of familial cancer risk for three genetic services outcomes (ever had genetic counseling for cancer risk, ever discussed genetic testing for cancer risk with a provider, and ever had genetic testing for cancer risk). Multivariable logistic regression models were used to estimate the association of familial cancer risk and other demographic and health variables with genetic services. Most women (87.67%) in this study were at low risk based on self-reported family history of breast and ovarian cancer, 10.65% were at medium risk, and 1.68% were at high risk. Overall, very small numbers of individuals had ever had genetic counseling (2.78%), discussed genetic testing with their physician (4.55%) or had genetic testing (1.64%). Across all genetic services outcomes, individuals who were at higher familial risk were more likely to have had genetic counseling than those at lower risk (high risk: aOR = 5.869, 95% CI = 2.911–11.835; medium risk: aOR = 4.121, 95% CI = 2.934–5.789), discussed genetic testing (high risk: aOR = 5.133, 95% CI = 2.699–9.764; medium risk: aOR = 3.649, 95% CI = 2.696–4.938), and completed genetic testing (high risk: aOR = 8.531, 95% CI = 3.666–19.851; medium risk aOR = 3.057, 95% CI = 1.835–5.094). Those who perceived themselves as being more likely to develop cancer than the average woman were more likely to engage in genetic counseling (aOR = 1.916, 95% CI = 1.334–2.752), discuss genetic testing (aOR = 3.314, 95% CI = 2.463–4.459) or have had genetic testing (aOR = 1.947, 95% CI = 1.13–3.54). Personal cancer history was also a significant predictor of likelihood to have engaged in genetic services. Our findings highlight: (1) potential under-utilization of cancer genetic services among high risk populations in the U.S. and (2) differences in genetic services use based on individual’s characteristics such as self-reported familial risk, personal history, and beliefs about risk of cancer. These results align with other studies which have noted that awareness and use of genetic services are low in the general population and likely not reaching individuals who could benefit most from screening for inherited cancers. Efforts to promote public awareness of familial cancer risk may lead to better uptake of cancer genetic services.

PurposeApproximately 5–10% of breast and up to 25% of ovarian cancer cases are hereditary, predominantly associated with germline BRCA1/2 pathogenic variants. Identifying these mutations is essential for personalized treatment, prevention strategies, and cascade testing in families. However, integrating genetic testing into routine care faces substantial barriers globally and within Switzerland.MethodsThis retrospective, quantitative study analyzed 209 patients treated for non-mucinous ovarian carcinoma or primary breast cancer at the Women’s Cantonal Hospital, Lucerne (2017–2022). All patients met Swiss clinical (SAKK) criteria for genetic testing, and recommendations for counseling were documented. Data were collected via anonymized questionnaires evaluating demographics, counseling experiences, emotional responses, and testing barriers. Statistical analyses examined factors influencing counseling uptake, including timing, referral source, education, and informational resources.ResultsOut of 73 respondents (32.6% response rate), 70 questionnaires were analyzed. Acceptance of genetic counseling was 81.4%. Recommendations by gynecologists significantly enhanced uptake (p = 0.002), especially when provided postoperatively or at diagnosis (p = 0.011). Higher education levels (p = 0.009) and prior informational materials (p = 0.014) positively influenced acceptance. Emotional responses differed, with breast cancer patients reporting more fear, whereas ovarian cancer patients reported greater curiosity. Family involvement supported patient engagement, while perceptions of minimal personal benefit and family disinterest were common reasons for declining.ConclusionTimely, well-communicated recommendations and informational resources significantly improve genetic counseling uptake among breast and ovarian cancer patients. Addressing systemic and patient-specific barriers will enhance equitable access, optimize targeted therapies and preventive strategies, and should be supported by national registries, qualitative research, and digital integration.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00404-025-08138-9.

MP47-20 UNIVERSAL GERMLINE GENETIC TESTING OF PATIENTS WITH NEWLY DIAGNOSED UPPER TRACT UROTHELIAL CARCINOMA: AN INTERIM ANALYSIS