Implementation of a Population-Based Cancer Family History Screening Program for Lynch Syndrome.

OBJECTIVES: Lynch syndrome increases risks for colorectal and other cancers. Though published Lynch syndrome cancer risk-management guidelines are effective for risk-reduction, the condition remains under-recognized. The Cancer Genetics Program at an academic medical center implemented a population-based cancer family history screening program, Detecting Unaffected Individuals with Lynch syndrome, to aid in identification of individuals with Lynch syndrome. METHODS: In this retrospective cohort study, simple cancer family history screening questionnaires were used to identify those at risk for Lynch syndrome. Program navigators triaged and educated those who screened positive about hereditary cancer, and genetic counseling and testing services, offering genetic counseling if eligible. Genetic counseling was provided primarily via telephone. Genetic counselors performed hereditary cancer risk assessment and offered genetic testing via hereditary cancer panels to those eligible. Remote service delivery models via telephone genetic counseling and at-home saliva testing were used to increase access to medical genetics services. RESULTS: This program screened 212,827 individuals, over half of whom were considered underserved, and identified 133 clinically actionable genetic variants associated with hereditary cancer. Of these, 47 (35%) were associated with Lynch syndrome while notably, 70 (53%) were not associated with hereditary colorectal cancer. Of 3,344 patients offered genetic counseling after initial triage, 2,441 (73%) elected to schedule the appointment and 1,775 individuals (73%) completed genetic counseling. Among underserved patients, telephone genetic counseling completion rates were significantly higher than in-person appointment completion rates (P < .05). While remote service delivery improved appointment completion rates, challenges with genetic test completion using at-home saliva sample collection kits were observed, with 242 of 1592 individuals (15%) not completing testing. CONCLUSION: Population-based cancer family history screening and navigation can help identify individuals with hereditary cancer syndromes across diverse patient populations, but logistics of certain downstream service delivery models can impact outcomes.

Genetic variants with discordant classifications: An assessment of genetic counselor attitudes and practices.

Discordant variant classifications (DVCs) can impact patient care and pose challenges for clinicians. A survey-based study was conducted to examine genetic counselor (GC) attitudes and practices related to DVCs. Most GCs (202/229, 88%) in the study provide direct patient care across clinical specialties; review patients' genetic test results to determine if reported genetic variants have DVCs (176/202, 88%); and inform patients of known DVCs that impact medical management (165/202, 82%). DVC review, which takes 41 min (range: 5-240) on average per week, is typically prompted by the identification of a variant of uncertain significance (VUS) (160/176, 90%) and is primarily conducted using public databases (176/176, 100%). While most GCs felt it would not be ethical to knowingly provide different medical management recommendations to patients with the same genetic variant (152/229, 66%), they also stated they would rely on the variant classification on the test report (141/229, 61%) and/or the patient's personal/family history (188/229, 82%) to determine which classification to follow if a DVC is identified. Both factors are patient-specific and, inherently, could lead to differing recommendations. When posed with a hypothetical scenario in which two patients have the same genetic variant, but test reports show a DVC (pathogenic vs VUS), most GCs (179/229, 78.2%) stated they would make the same recommendation for both patients regardless of management guidelines. One-third (52/179, 29.1%) cited patient-specific factors, such as personal/family history, would impact their recommendations. Disagreements about whether the pathogenic or VUS classification should be used to make medical management recommendations were noted. Differing practices and opinions on how to manage patients with DVCs, as well as the fact that most GCs (209/229, 91.3%) have consulted with colleagues on this matter, highlight the need for more professional guidance to ensure equitable patient care.

Racial and Ethnic Disparities in Germline Genetic Testing of Patients With Young-Onset Colorectal Cancer.

BACKGROUND & AIMS: Up to 20% of younger patients (age <50 years) diagnosed with colorectal cancer (CRC) have germline mutations in cancer susceptibility genes. Germline genetic testing may guide clinical management and facilitate earlier intervention in affected relatives. Few studies have characterized differences in genetic testing by race/ethnicity. METHODS: We identified young adults (age 18-49 years) diagnosed with CRC between 2009 and 2017 in 2 health systems in Dallas, TX. We evaluated referral to genetic counseling, attendance at genetic counseling appointments, and receipt of germline genetic testing by race/ethnicity. RESULTS: Of 385 patients with young-onset CRC (median age at diagnosis 44.4 years), 176 (45.7%) were Hispanic, 98 (25.4%) non-Hispanic Black, and 111 (28.8%) non-Hispanic White. Most patients (76.9%) received immunohistochemistry (IHC) for mismatch repair proteins, and there was no difference in receipt of IHC by race/ethnicity. However, a lower proportion of Black patients were referred to genetic counseling (50.0% vs White patients 54.1% vs Hispanic patients 65.9%; P = .02) and attended genetic counseling appointments (61.2% vs 81.7% White patients vs 86.2% Hispanic patients; P < .01). Of 141 patients receiving genetic testing, 38 (27.0%) had a pathogenic or likely pathogenic variant in a cancer susceptibility gene. An additional 33 patients (23.4%) had variants of uncertain significance, of which 84.8% occurred in racial/ethnic minorities. CONCLUSIONS: In a diverse population of patients diagnosed with young-onset CRC, we observed racial/ethnic differences in referral to and receipt of germline genetic testing. Our findings underscore the importance of universal genetic testing to address racial/ethnic disparities in young-onset CRC.

Standardized applications for genetic counseling graduate programs: Opinions of program directors.

Genetic Counseling Graduate Programs (GCGPs) have progressively increased in number and class size, and implementation of the National Matching Services in 2018 was a major step toward streamlining the admissions process. Standardized applications (SAs), which have been incorporated into the admissions process for undergraduate studies as well as several professional graduate programs, could also be considered for GCGPs. In this study, we assessed the opinions of GCGP Program Directors (PDs) regarding the implementation of an SA for GCGP admissions processes. GCGP PDs participated in an anonymous online survey designed to evaluate interest in an SA and assess perceived implementation barriers. The survey collected GCGP and PD demographic information, data on current application components, and PD opinions of an SA. Thirty PDs were included in this study, and just over half (n = 16/30, 53.3%) reported their current application structure would allow for SA implementation. While 40% (n = 12/30) of respondents anticipated an SA would benefit GCGPs, an additional 23.3% (n = 7/30) anticipated no impact to GCGPs. Most respondents (n = 26/30, 86.6%) anticipated that an SA would be beneficial for GCGP applicants. The main perceived benefit to GCGPs was an efficient application process, while perceived benefits to applicants included decreased redundancy and increased application access. Perceived harms to GCGPs included more generic applications, while perceived harms to applicants included increased competition for admission to individual GCGPs. The most common SA implementation barrier cited by respondents was current administrative structures. This study demonstrates that while GCGP leadership largely perceives an SA to be beneficial for applicants, opinions on impact to GCGPs vary. While the majority of respondents perceive implementation of an SA to be feasible, there are implementation barriers that must be addressed. Interestingly, GCGP leadership had mixed perceptions about the structure of a hypothetical SA, and thus overall impact, demonstrating the need for further study.

Clinicopathological Features and Outcomes in Individuals with Breast Cancer and ATM, CHEK2, or PALB2 Mutations.

INTRODUCTION: The moderate-penetrance germline mutations ATM, CHEK2, and PALB2 are implicated in an increased risk of the development of breast cancer. Whether these mutations provide clinical utility to guide treatment strategies and prognosis remains unknown. METHODS: A retrospective case-control study from a tertiary institution compared patients with stage 0-III breast cancer, and positive for ATM, CHEK2, or PALB2 mutations, with a matched cohort selected by randomization and negative for mutations. Data acquisition included demographics, histopathologic, treatment, and clinical outcome variables. RESULTS: A total of 145 patients with breast cancer (144 female and 1 male) were analyzed-74 mutation-positive patients (24 ATM, 26 CHEK2, 24 PALB2) and 71 mutation-negative patients. Mutation-positive patients compared with mutation-negative patients had increased family history of breast cancer (79.7 vs. 52.9%, p < 0.001) and tumor size > 2.0 cm (63.1% vs. 42.3%, p = 0.015). Patients with prior knowledge of mutational status were more likely to proceed with total mastectomy and prophylactic mastectomy (74.5% vs. 25.5%, p < 0.02; and 65.5% vs. 34.5%, p < 0.001, respectively). The unadjusted recurrence rate was higher in mutation-positive patients compared with mutation-negative patients (24.3 vs. 8.5%, p = 0.01), although mutation status was not predictive for recurrence in Cox regression analysis. CONCLUSIONS: Patients positive for ATM, CHEK2, or PALB2 mutations had increased tumor size and were more likely to undergo extensive surgeries. Mutation status was not predictive of recurrence, although this lack of effect may have been mitigated by lower rates of recurrence in those who pursued total mastectomy. Further studies are needed to confirm these findings.

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 1.2021.

Identifying individuals with hereditary syndromes allows for timely cancer surveillance, opportunities for risk reduction, and syndrome-specific management. Establishing criteria for hereditary cancer risk assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provides recommendations for the assessment and management of patients at risk for or diagnosed with high-risk colorectal cancer syndromes. The NCCN Genetic/Familial High-Risk Assessment: Colorectal panel meets annually to evaluate and update their recommendations based on their clinical expertise and new scientific data. These NCCN Guidelines Insights focus on familial adenomatous polyposis (FAP)/attenuated familial adenomatous polyposis (AFAP) syndrome and considerations for management of duodenal neoplasia.

Adapting genetic counseling operations amidst the COVID-19 pandemic.

The COVID-19 pandemic caused significant disruptions to the delivery of genetic counseling services and clinical operations. Understanding how these pivots in practice affected patient care across both a county hospital system and academic medical center can help provide models of clinical operations for other genetic counselors. Programmatic data were analyzed between March 18, 2020 and September 18, 2020, including visit completion rates and genetic testing completion outcomes for genetic counseling services during the COVID-19 pandemic. In addition to analyzing the effects on patient care, we provide commentary on technological adaptations that aided our operations, billing practices, onboarding and engaging new and existing staff, and coordination of education and outreach opportunities. Through this work, we highlight barriers encountered and successful adaptations that will influence future clinical practices and may guide other providers in the development of strategies to meet their clinical and operational needs.

Prevalence of Variant Reclassification Following Hereditary Cancer Genetic Testing.

Importance: Variant reclassification is an important component of hereditary cancer genetic testing; however, there are few published data quantifying the prevalence of reclassification. Objective: Retrospective cohort study of individuals who had genetic testing from 2006 through 2016 at a single commercial laboratory. Design, Setting, and Participants: A retrospective cohort of individuals who had genetic testing between 2006 and 2016 at a single commercial laboratory was assessed. Variants were classified as benign, likely benign, variant of uncertain significance, likely pathogenic, or pathogenic. Retrospective chart reviews were conducted for patients from the University of Texas Southwestern (UTSW) Medical Center. Exposures: Hereditary cancer genetic testing. Main Outcomes and Measures: Frequency of and time to amended reports; frequency and types of variant reclassification. Results: From 2006 through 2018, 1.45 million individuals (median [interquartile range] age at testing, 49 years [40.69-58.31 years], 95.6% women) had genetic testing, and 56.6% (n = 821 724) had a personal history of cancer. A total of 1.67 million initial tests were reported and 59 955 amended reports were issued due to variant reclassification. Overall, 6.4% (2868 of 44 777) of unique variants were reclassified. Reclassification to a different clinical category was rare among unique variants initially classified as pathogenic or likely pathogenic (0.7%, 61 of 9112) or benign or likely benign (0.2%, 15 of 8995). However, 7.7% (2048 of 26 670) of unique variants of uncertain significance were reclassified: 91.2% (1867 of 2048) were downgraded to benign or likely benign (median time to amended report, 1.17 years), 8.7% (178 of 2048) were upgraded to pathogenic or likely pathogenic variants (median time to amended report, 1.86 years). Because most variants were observed in more than 1 individual, 24.9% (46 890 of 184 327) of all reported variants of uncertain significance were reclassified. Conclusions and Relevance: Following hereditary cancer genetic testing at a single commercial laboratory, 24.9% of variants of uncertain significance were reclassified, which included both downgrades and upgrades. Further research is needed to assess generalizability of the findings for other laboratories, as well as the clinical consequences of the reclassification as a component of a genetic testing program.

Genetic Counseling Assistants: an Integral Piece of the Evolving Genetic Counseling Service Delivery Model.

This study explores the potential impact of the genetic counseling assistant (GCA) position on the efficiency of the genetic counseling field, evaluates attitudes regarding expansion of the genetic counseling field to include the GCA, and presents data on GCA endeavors and GCA job tasks as reported by GCAs, certified genetic counselors (CGCs), and program directors (PDs). Data on GCA roles and attitudes toward different aspects of the GCA position were collected via surveys of CGCs who have worked with GCAs, PDs who have and have not had experience with GCAs in their programs, and GCAs. We analyzed responses from 63 individuals: 27 PDs, 22 CGCs, and 14 GCAs. GCAs' impact on efficiency was calculated via internal analysis of genetic patient volume per genetic counselor within the University of Texas Southwestern (UTSW) patient database prior to, and since the addition of, a GCA to the practice. The response rates for PDs, CGCs, and GCAs were 27 %, 79 %, and 61 %, respectively. Every CGC stated the GCA increased their efficiency. CGCs with a GCA reported a 60 % average increase in patient volume. This figure was congruent with internal data from the UTSW cancer genetics program (58.5 % increase). Appropriate responsibilities for GCAs as reported by CGCs and PDs (>90 %) include: data entry, shipping tests, administrative tasks, research, and ordering supplies. Regarding GCAs delivering test results, there was response variation whether this should be a job duty: 42 % of CGCs agreed to GCAs delivering negative results to patients, compared to 22 % of program directors. Twenty-two percent of PDs expressed concern about the job title "Genetic Counseling Assistant." Ninety percent of CGCs felt that GCA was a career path to becoming a CGC, compared to 42 % of PDs. Eighty-three percent of GCAs who decided to apply to CGC graduate programs were accepted. We conclude the addition of a GCA to a genetic counseling practice contributes to increased efficiency and is one way to expand the reach of the profession.

The current state of cancer genetic counseling access and availability.

PURPOSE: Genetic risk assessment and counseling by a qualified genetics professional are recommended to ensure high-quality care for individuals at risk of hereditary cancer. Timely access to genetic services provided by a genetic counselor (GC) is essential, especially in cases where genetic testing results may affect impending surgical decisions. METHODS: A survey of GCs who specialize in cancer genetics was performed to assess service delivery models and ability to accommodate urgent cases. RESULTS: Over half of all respondents indicated that urgent patients can be seen for consultation the same day or within 1-2 business days, and almost all respondents indicated that urgent cases can be seen within 1 week. Most respondents indicated that urgent cases are seen by a GC only with no physician involved. CONCLUSIONS: The results of this survey of GCs demonstrate that timely access to cancer genetic counseling by GCs in an urgent setting is available.Genet Med 18 4, 410-412.