Transferring care to enhance access to early-phase cancer clinical trials: Protocol to evaluate a novel program.

Involving diverse populations in early-phase (phase I and II) cancer clinical trials is critical to informed therapeutic development. However, given the growing costs and complexities of early-phase trials, trial activation and enrollment barriers may be greatest for these studies at healthcare facilities that provide care to the most diverse patient groups, including those in historically underserved communities (e.g., safety-net healthcare systems). To promote diverse and equitable access to early-phase cancer clinical trials, we are implementing a novel program for the transfer of care to enhance access to early-phase cancer clinical trials. We will then perform a mixed-methods study to determine perceptions and impact of the program. Specifically, we will screen, recruit, and enroll diverse patients from an urban, integrated safety-net healthcare system to open and active early-phase clinical trials being conducted in a university-based cancer center. To evaluate this novel program, we will: (1) determine program impact and efficiency; and (2) determine stakeholder experience with and perceptions of the program. To achieve these goals, we will conduct preliminary cost analyses of the program. We will also conduct surveys and interviews with patients and caregivers to elucidate program impact, challenges, and areas for improvement. We hypothesize that broadening access to early-phase cancer trials conducted at experienced centers may improve equity and diversity. In turn, such efforts may enhance the efficiency and generalizability of cancer clinical research.

Heterogeneity in familial clustering of metabolic syndrome components in the multiethnic GENNID study.

OBJECTIVE: Metabolic syndrome (MetS) is defined by clustering of cardiometabolic components, which may be present in different combinations. The authors evaluated clustering in individuals and extended families within and across ancestry groups. METHODS: The prevalence of different combinations of MetS components (high fasting glucose, low high-density lipoprotein cholesterol, high triglycerides, high blood pressure, and abdominal obesity) was estimated in 1651 individuals (340 families) self-reporting as European American (EA), Hispanic/Mexican American (MA), African American (AA), and Japanese American (JA). Odds ratios were estimated using logistic regression with generalized estimating equations comparing individual MetS components, number, and combinations of components for each ancestry group versus EA. RESULTS: Clustering of all five components (Combination #16) was more prevalent in EA (29.9%) and MA (25.2%) individuals than in AA (18.7%) and JA (15.5%) individuals. Compared with EA individuals, AA individuals were 64% and 66% less likely to have high triglycerides and low high-density lipoprotein cholesterol, whereas JA individuals were 85% and 56% less likely to have abdominal obesity and high blood pressure, respectively. Compared with EA individuals, the odds of having two, four, or five components were at least 77% lower in JA individuals, whereas the odds of having three, four, or five components were at least 3.79 times greater in MA individuals. CONCLUSIONS: Understanding heterogeneity in MetS clustering may identify factors important in reducing health disparities.

Practices and Views of US Oncologists and Genetic Counselors Regarding Patient Recontact After Variant Reclassification: Results of a Nationwide Survey.

PURPOSE: Over a 5-year or 10-year period, between 6% and 15% of germline cancer genetic variants undergo reclassification. Up-to-date interpretation can clarify a variant's clinical significance and guide patient management. As the frequency of reclassifications increase, the issue of whether, how, when, and which providers should recontact patients with information about reclassification becomes important. However, the field lacks research evidence and definitive guidance from professional organizations about how providers should recontact patients. We compared the perspectives of US oncologists and cancer genetic counselors (GCs) to describe their practices and views regarding recontact. MATERIALS AND METHODS: We developed a survey using themes identified from semistructured interviews with oncologists and GCs and administered it in a national sample of oncologists and GCs between July and September 2022. RESULTS: In total, 634 respondents completed the survey including 349 oncologists and 285 GCs. On frequency of recontacting patients with reclassified results, 40% of GCs reported recontacting often compared with 12.5% of oncologists. Neither group reported recording patient preference for recontact on electronic medical record (EMR). Both groups agreed that all reclassified variants, even those that do not affect clinical management, should be returned to patients. They also reported that recontact via EMR messages, mailed letters, and phone calls from GC assistants were more suitable for downgrades. By contrast, face-to-face meetings and phone calls were preferred for upgrades. Remarkably, oncologists were more likely to endorse face-to-face return of results and were more likely to endorse return through a nongenetics provider compared to GCs. CONCLUSION: These data on current recontact practices and opinions provide a foundation for developing guidelines with explicit recommendations on patient recontact that can help maximize clinical effect while considering provider preferences for recontact within resource-constrained genomic practice settings.

A multicenter study of clinical impact of variant of uncertain significance reclassification in breast, ovarian and colorectal cancer susceptibility genes.

BACKGROUND: Clinical interpretation of genetic test results is complicated by variants of uncertain significance (VUS) that have an unknown impact on health but can be clarified through reclassification. There is little empirical evidence regarding VUS reclassification in oncology care settings, including the prevalence and outcomes of reclassification, and racial/ethnic differences. METHODS: This was a retrospective analysis of persons with and without a personal history of cancer carrying VUS (with or without an accompanying pathogenic or likely pathogenic [P/LP] variant) in breast, ovarian, and colorectal cancer predisposition genes seen at four cancer care settings (in Texas, Florida, Ohio, and New Jersey) between 2013 and 2019. RESULTS: In 2715 individuals included in the study, 3261 VUS and 313 P/LP variants were reported; 8.1% of all individuals with VUS experienced reclassifications and rates varied significantly among cancer care settings from 4.81% to 20.19% (overall p < 0.001). Compared to their prevalence in the overall sample, reclassification rates for Black individuals were higher (13.6% vs. 19.0%), whereas the rates for Asian individuals were lower (6.3% vs. 3.5%) and rates for White and Hispanic individuals were proportional. Two-year prevalence of VUS reclassification remained steady between 2014 and 2019. Overall, 11.3% of all reclassified VUS resulted in clinically actionable findings and 4.6% subsequently changed individuals' clinical managements. CONCLUSIONS: The findings from this large multisite study suggest that VUS reclassification alters clinical management, has implications for precision cancer prevention, and highlights the need for implementing practices and solutions for efficiently returning reinterpreted genetic test results.

Use of breast surveillance between women with pathogenic variants and variants of uncertain significance in breast cancer susceptibility genes.

BACKGROUND: Use of surveillance mammography and magnetic resonance imaging (MRI) has been understudied among women with variant of uncertain significance (VUS) compared to pathogenic and likely pathogenic variants (P/LP). METHODS: Using data from two cancer settings, we calculated use of risk-reducing mastectomy (RRM) and surveillance during each 13-month span after genetic testing up to 6 years afterwards for a cohort of genetically elevated risk women. RESULTS: Of 889 women, VUS carriers were less likely to undergo RRM compared to those with P/LP (hazard ratio [HR], 0.17; p = <.001) and high-risk women were more likely to undergo RRM than average-risk women (HR, 3.91; p = .005). Longitudinally, surveillance use among unaffected women decreased from 49.8% in the first year to 31.2% in the sixth year after genetic testing. In comparison, a greater proportion of women with a personal history of breast cancer underwent surveillance, which increased from 59.3% in the first year to 63.6% in the sixth year after genetic testing. Mammography rates did not differ between women with P/LP and VUS within the first 13 months after genetic testing and up to 4 years afterward. Over the first 4 years after genetic testing, women with VUS were less likely to undergo annual MRIs compared to P/LP. CONCLUSION: The authors found that VUS, whether in high or moderate penetrance breast cancer susceptibility genes, was associated with lower use of annual breast MRI compared to P/LP variants and equivalent use of annual mammography. These results add important evidence regarding VUS-related breast surveillance.

Are beliefs about the importance of genetics for cancer prevention and early detection associated with high risk cancer genetic testing in the U.S. Population?

Public attitudes towards germline genetic testing for inherited cancers have been found to be generally positive. Past research demonstrated that diverse causal beliefs and contextual factors are associated with uptake of genetic testing. However, it is unclear how beliefs about genetically informed cancer prevention and early detection ultimately shape testing behaviors. We used data from the National Health Information National Trends Survey (HINTS 5 Cycle 4) to evaluate these beliefs and the relationship between beliefs related to cancer genetics and participation in cancer genetic testing. Overall, 5.24% of the total weighted sample underwent cancer genetic testing, of whom 70.5% (n = 141) had no personal history of cancer, whereas others had a personal diagnosis of breast, ovarian, or colorectal cancer (23.0%), or other cancers (6.5%). In adjusted multivariable analysis, testing was positively associated with personal history of breast, ovarian, or colorectal cancer (OR = 28.37, 95% CI: 10.19-79.04), female sex (OR = 2.97, 95% CI: 1.41-6.26), having high cancer worry (OR = 4.78, 95%: 2.19-10.45), and negatively associated with being Hispanic (OR = 0.37, 95%: 0.16-0.86) or non-Hispanic Asian (OR = 0.12, 95% CI: 0.04-0.33). Belief in the importance of genetics for early detection of cancer was associated with testing (OR = 18.03, 95% CI: 4.07-79.79), whereas belief in the importance of genetics for cancer prevention was not. The association between testing and belief about the importance of genetics for early detection of cancer, but not cancer prevention, is a surprising finding that warrants further research. Better understanding of these beliefs and their potential impact on test uptake may inform population genetic testing efforts.

Helping Patients Understand and Cope with BRCA Mutations.

PURPOSE OF REVIEW: Individuals carrying germline mutations in BRCA1/2 have unique psychosocial and educational needs that must be met to ensure informed clinical decision-making. In this review, we highlight the strategies used in clinical practice to support patients' needs as well as currently available pre- and post-disclosure support interventions. RECENT FINDINGS: Clinical risk communication is complicated by the uncertainty associated with gene penetrance, inconclusive results, variable effectiveness of surgical and screening interventions, and inadequate awareness of clinical genetics. Interventions to support patients' psychosocial needs, and strategies for effective and scalable clinical risk communication are in routine use and largely effective at meeting patients' needs. Research is underway to develop newer supportive resources; however, the inadequate representation of all mutation carriers persists. Effective clinical risk communication strategies, decision support aids, written educational materials, and supportive psychosocial tools can together have a large impact on meeting BRCA carriers' supportive needs.

Home-Based Spirometry Telemonitoring After Allogeneic Hematopoietic Cell Transplantation: Mixed Methods Evaluation of Acceptability and Usability.

BACKGROUND: Home-based spirometry (HS) allows for the early detection of lung complications in recipients of an allogeneic hematopoietic cell transplant (AHCT). Although the usability and acceptability of HS are critical for adherence, patient-reported outcomes of HS use remain poorly understood in this setting. OBJECTIVE: The aim of this study is to design a longitudinal, mixed methods study to understand the usability and acceptability of HS among recipients of AHCT. METHODS: Study participants performed HS using a Bluetooth-capable spirometer that transmitted spirometry data to the study team in real time. In addition, participants completed usability questionnaires and in-depth interviews and reported their experiences with HS. Analysis of interview data was guided by the constructs of performance expectancy, effort expectancy, and social influence from the Unified Theory of Acceptance and Use of Technology model. RESULTS: Recipients of AHCT found HS to be highly acceptable despite modest technological barriers. On average, participants believed that the HS was helpful in managing symptoms related to AHCT (scores ranging from 2.22 to 2.68 on a scale of 0-4) and for early detection of health-related problems (score range: 2.88-3.12). Participants viewed HS favorably and were generally supportive of continued use. No significant barriers to implementation were identified from the patient's perspective. Age and gender were not associated with the patient perception of HS. CONCLUSIONS: Study participants found HS acceptable and easy to use. Some modifiable technical barriers to performing HS were identified; however, wider implementation of pulmonary screening is feasible from the patient's perspective.

Increasing referral of at-risk women for genetic counseling and BRCA testing using a screening tool in a community breast imaging center.

BACKGROUND: Genetic evaluation and testing for hereditary breast and ovarian cancer (HBOC) remain suboptimal. The authors evaluated the feasibility of using a screening tool at a breast imaging center to increase HBOC assessment referrals. METHODS: A brief questionnaire based on the National Comprehensive Cancer Network HBOC genetic counseling referral guidelines was developed and added to the standard intake forms of patients undergoing mammography at a community breast imaging center from 2012 through 2015. Patients who met the criteria in the guidelines were referred for genetic counseling. RESULTS: A total of 34,851 patients were screened during the study period, and 1246 (4%) patients were found to be eligible for referral; 245 of these patients made a genetic counseling appointment, and 142 patients received genetic counseling. Forty patients (28%) had a personal history of breast cancer but were not previously tested. Following counseling, 105 patients were tested for BRCA1/2. Eight patients (8%) tested positive for a pathogenic mutation and nine (9%) had a variant of unknown significance. Although they tested negative, many patients met the criteria to add breast magnetic resonance imaging to their screening due to greater than 20% lifetime breast cancer risk based on their family cancer history. This study led to improved clinical risk management in 67% of the patients who underwent genetic counseling. CONCLUSIONS: This study shows that large-scale screening of patients for HBOC syndromes at time of breast imaging is practical and highly feasible. The screening tool identified women with actionable BRCA1/2 mutations and mutation-negative but high-risk women, leading to significant changes in their risk management; these women would otherwise have been missed. LAY SUMMARY: Hereditary breast and ovarian cancer (HBOC) caused by pathogenic mutations in breast cancer genes (BRCA1/BRCA2) increase an individual's lifetime risk of getting HBOC. Identifying these high-risk individuals and using proven preventive clinical risk management strategies can significantly reduce their lifetime risk of HBOC. Using an innovative family cancer history questionnaire, 34,000 women were screened at a community breast imaging center, and genetic counseling and testing were provided to eligible women from the screening. Several women at high risk for HBOC were identified and this led to positive clinical risk management changes. These women would have been missed if not for intervention.

Clinical Cancer and Direct-to-Consumer Genetic Test Result-Sharing Behavior: Findings from HINTS 2020.

INTRODUCTION: Sharing genetic test results with different stakeholders such as family members, healthcare providers and genetic counselors (HCP/GCs), spouses/partners, and friends is a health behavior of clinical importance in genomic medicine. METHODS: Using nationally representative population-based data collected from the Health Information National Trends Survey (HINTS 5, cycle 4), we identified the prevalence and factors associated with genetic test result-sharing behavior for high-risk cancer tests, genetic health risk tests, and ancestry tests within four groups: HCP/GCs, first-degree relatives (FDRs), spouse/partner, and friend/other. RESULTS: Overall, 68.4% of those who underwent high-risk cancer genetic testing shared their results with FDRs, whereas 89.9% shared with HCP/GCs. In adjusted multivariable analyses, women were nine times more likely than men to share (p = 0.006), and those with a personal history of cancer were less likely to share with HCP/GCs (OR = 0.025, p ≤ 0.001). Of those tested for genetic health risk, 66.5% shared with HCP/GCs, 38.7% with FDRs, 66.6% with a spouse/partner, 12.8% with a friend, and 14.1% did not share results with anyone. Of those who underwent ancestry testing, very few shared results with HCP/GCs (2.6%), whereas modest sharing was reported with FDRs, spouses/partners, and friends. DISCUSSION: These data add empirical evidence about the population prevalence of genetic information sharing and serve as a metric for public engagement with genetic testing.

Contralateral Prophylactic Mastectomy among Women with Pathogenic Variants in BRCA1/2: Overall Survival, Racial, and Ethnic Differences.

Background: Patients with unilateral breast cancer carrying pathogenic variants in BRCA1/2 have the option to undergo contralateral prophylactic mastectomy (CPM). However, differences in CPM use and survival outcomes following CPM are poorly understood in this high-risk population, in part due to a lack of data from contemporary clinical cohorts. The objective of this study was to evaluate post-CPM overall survival (OS) and related racial/ethnic differences in a contemporary clinical cohort. Methods: We retrospectively reviewed the medical records of women with a personal history of unilateral breast cancer carrying pathogenic variants in BRCA1/2 who were diagnosed between 1996 and 2012. Genetic test results, self-reported demographic characteristics, and clinical factors were abstracted from electronic medical records. Results: Of 144 BRCA-positive patients, the majority were White (79.2%, n = 114). Overall, 56.1% (n = 81) of all BRCA1/2 carriers chose to undergo CPM, with no racial/ethnic difference in CPM election (p = 0.78). Of 81 patients who underwent CPM, there is strong evidence of a difference in survival between the racial/ethnic groups, with White patients having the highest OS compared to non-White patients (p = 0.001). Of the 63 patients who did not undergo CPM, there is no racial/ethnic difference in overall survival (p = 0.61). In multivariable cox regression, adjusted for demographic and clinical characteristics, OS was significantly lower among non-Whites than in Whites (HR = 0.39, p = 0.04). Conclusions: Evaluation of a contemporary clinical cohort of BRCA-positive women with unilateral breast cancer showed no racial/ethnic difference in CPM use, but there was a significant difference in post-CPM overall survival.

Uptake of cancer risk management strategies among women who undergo cascade genetic testing for breast cancer susceptibility genes.

BACKGROUND: Uptake of cancer risk management based on inherited predispositions, which encompasses bilateral mastectomy (BLM), bilateral salpingo-oophorectomy (BSO), and intensified screening, is the primary motivation for cascade testing for hereditary breast and ovarian cancer (HBOC). However, long-term outcome data for cascade testers are lacking. METHODS: Medical records were abstracted for all unaffected women with pathogenic variants in HBOC genes from 2 cancer hospitals (2013-2019) with at least 1 year of follow-up to compare the uptake of surgery and screening between cascade and noncascade testers. RESULTS: Cascade testers (79.8%) were younger than noncascade testers (mean age, 37.6 vs 43.5 years; P = .002). Among women aged ≥40 years, 43% underwent BLM, and 71.6% underwent BSO, with no significant difference in uptake between cascade and noncascade testers. The mean time to BSO among cascade testers was shorter among women aged ≥40 years versus those aged <40 years (11.8 vs 31.9 months; P = .04); no such difference was observed among noncascade testers. Mammography and breast magnetic resonance imaging rates were low in the recorded 6 years for both groups after genetic counseling. CONCLUSIONS: Management uptake among cascade testers is high with rates comparable to those for unaffected BRCA-positive women. A large proportion of women act on cascade test results, and this represents a novel report of utilization of cancer management strategies.

Clinical management among individuals with variant of uncertain significance in hereditary cancer: A systematic review and meta-analysis.

Improper medical use of variant of uncertain significance (VUS) remains a concern in hereditary cancer genetic testing. The goal of this study was to assess the association between pathogenic and likely pathogenic (P/LP), VUS, and benign and likely benign (B/LB) genetic test results and cancer-related surgical and screening management. Systematic searches of Medline, Embase, EBSCO CINAHL Plus, and PsycINFO were conducted from 1946 to August 26, 2020. Eligible studies included individuals with cancer genetic test result and surgical or screening management outcomes. We reviewed 885 abstracts and 22 studies that reported relevant surgical and screening outcomes were included. Meta-analysis revealed significantly higher surgical rates among individuals with P/LP than among those with VUS for therapeutic mastectomy with contralateral prophylactic mastectomy (OR = 7.35, 95% CI, 4.14-13.64), prophylactic mastectomy (OR = 3.05, 95% CI, 1.5-6.19), and oophorectomy (OR = 6.46, 95% CI, 3.64-11.44). There were no significant differences in therapeutic mastectomy, or breast conservation or lumpectomy rates between individuals with P/LP and VUS, or in any outcomes between patients with VUS and B/LB. Studies evaluating screening outcomes were limited, and results were conflicting. Comprehensive analysis do not indicate that a significant number of individuals with VUS results undergo inappropriate clinical management.

Factors Influencing Discussion of Cancer Genetic Testing with Health-Care Providers in a Population-Based Survey.

INTRODUCTION: Discussion of cancer genetic testing with health-care providers (HCPs) is necessary to undergo testing to inform cancer risk assessment and prevention. Given the rapid evolution in genetic testing practice in oncology, we describe the current landscape of population-level cancer genetic testing behaviors. METHODS: A questionnaire including items regarding discussion of cancer genetic testing with HCPs was administered to a nonprobability sample (N = 2,029) of the Texas population. RESULTS: Overall, 11% of respondents discussed cancer genetic testing with HCPs. In multivariable analysis, discussion was significantly related to having a personal history of breast/ovarian/colon cancer (OR = 11.57, 95% CI = 5.34-25.03), personal history of other cancer (OR = 3.18, 95% CI = 1.69-5.97), and health information-seeking behaviors (OR = 1.73, 95% CI = 1.12-2.66). Surprisingly, respondents who believed that inherited predispositions in addition to other modifiable risk factors cause cancer were less likely to discuss genetic testing compared to those who did not believe that inherited cancer predispositions cause cancer (OR = 0.54, 95% CI = 0.36-0.79). DISCUSSION: The high discussion rate may be attributed to increased public awareness of genetic testing and adoption of more inclusive clinical genetic testing guidelines. The findings suggest that efforts to increase public awareness of the utility of genetic testing on personalized cancer risk assessment and cancer prevention are needed.

The FamilyTalk randomized controlled trial: patient-reported outcomes in clinical genetic sequencing for colorectal cancer.

As genetics gains favor in clinical oncology, it is important to address patient concerns around confidentiality, privacy, and security of genetic information that might otherwise limit its utilization. We designed a randomized controlled trial to assess the social impact of an online educational tool (FamilyTalk) to increase family communication about colorectal cancer (CRC) risk and screening. Of 208 randomized participants, 149 (71.6%) returned six-month surveys. Overall, there was no difference in CRC screening between the study arms. Privacy and confidentiality concerns about medical and genetic information, reactions to genetic test results, and lifestyle changes did not differ between arms. Participants with pathogenic or likely pathogenic (P/LP) and variant of uncertain significance (VUS) results were more likely than those with negative results to report that the results accurately predicted their disease risks (OR 5.37, p = 0.02 and OR 3.13, p = 0.02, respectively). This trial demonstrated no evidence that FamilyTalk impacted patient-reported outcomes. Low power, due to the limited number of participants with P/LP results in the overall sample, as well as the short follow-up period, could have contributed to the null findings.

What improves the likelihood of people receiving genetic test results communicating to their families about genetic risk?

OBJECTIVE: We currently rely on probands to communicate genetic testing results and health risks within a family to stimulate preventive behaviors, such as cascade testing. Rates of guidelines-based cascade testing are low, possibly due to low frequency or non-urgent communication of risk among family members. Understanding what is being communicated and why may help improve interventions that increase communication and rates of cascade testing. METHODS: Participants (n = 189) who were to receive both positive and negative colorectal cancer (CRC) sequencing results completed surveys on family communication, family functioning, impact of cancer in the family, and future communication of risk and were participants in eMERGE3. Questions were taken from existing surveys and administered electronically using email and a web driven tool. RESULTS: Common family member targets of CRC risk communication, before results were received, were mothers and fathers, then sisters and grandchildren and finally, children and brothers. A communication impact score of 0.66 (sd = 0.83) indicated low-to-moderate communication impact. Age and education were significantly associated with frequency of familial communication, but not on the cancer-related impact of familial communication. CONCLUSIONS: There is infrequent communication about cancer risk from probands to family members. PRACTICE IMPLICATIONS: These results demonstrate an opportunity to help families improve communication.

Disclosure of familial implications of pathogenic variants in breast-cancer genes to patients: Opportunity for prompting family communication.

Familial communication of pathogenic genetic variants is necessary to maximize the clinical utility of genetic testing and its public health benefits. Insights to family communication considerations may be obtained from existing clinical documentation available in medical records. The goal of this study was to describe and characterize information about family communication of pathogenic variants and cascade genetic testing from genetic counseling summary notes. We completed structured content analysis of 656 summary notes describing pathogenic variants in breast cancer genes, for patients seen at a tertiary cancer center. Patients were 89.5% female, median age of 49 years, 32.6% non-White, and were counseled by 23 unique genetic counselors (GCs) with mean post-certification experience of 3.7 years. Cascade genetic testing was documented in 92.2% of all notes. Specific relatives (i.e., relationship to patient) who would benefit from genetic counseling and cascade testing were referenced in 33.1% of notes. Specific risk messaging was 2.5 times more likely to be present in notes of high- compared to moderate-risk genes (OR=2.53, 95% CI: 1.71-3.80), and when summary notes indicated the presence of a friend or relative (OR=2.29, 95% CI: 1.50-3.48). Summary notes frequently attempted to contextualize the patients' familial relationships by referencing positive family communication patterns (41.6%) or negative communication issues (2.4%) and included various strategies to address barriers to communication and assist relatives with cascade testing. Overall, GCs consistently documented family communication recommendations when pathogenic variants are identified on patients' genetic testing, albeit with heterogeneous use of specific communication prompts.

Impact of a Genetic Evaluation Initiative to Increase Access to Genetic Services for Adolescent and Young Adults at a Tertiary Cancer Hospital.

Purpose: Adolescents and young adults (AYAs) with cancer are at increased risk for inherited cancer predisposition syndromes. Genetic counseling (GC) is important for accurate risk assessment, diagnosis, and management of inherited cancers. Numerous barriers prevent AYA access to genetic services. This study describes outcomes of a genetic evaluation initiative (GEI) regarding utilization of genetic services among AYAs. Methods: To improve AYA access to GC, the AYA program at UT MD Anderson Cancer Center implemented GEI, a process for identifying and referring eligible patients for GC. We collected retrospective electronic medical record data between July 12, 2018 and July 12, 2019 to capture AYA's clinical characteristics, genetic referral, scheduled appointments, counseling, testing, and results. Results: In total, 516 AYAs were referred to the AYA clinic during the study period with a median age of first cancer diagnosis of 17 years. One hundred sixty-six AYAs were identified who would benefit from genetic evaluation, 57 (34.3%) of whom had previously undergone counseling. One hundred nine patients were recommended for referral to GC, and 64.2% (70/109) were referred by the AYA team. To date, 58.6% (41/70) met with a genetic counselor and 75.6% (31/41) completed genetic testing, which yielded 1 pathogenic, 2 uncertain, and 29 benign results. Conclusion: The GEI resulted in a 72.0% relative increase in the rate of GC utilization and represents a novel approach to increasing AYA patient access to cancer genetic services in this population.

Relationship between genetic knowledge and familial communication of CRC risk and intent to communicate CRCP genetic information: insights from FamilyTalk eMERGE III.

Successful translation of genetic information into patient-centered care and improved outcomes depends, at least in part, on patients' genetic knowledge. Although genetic knowledge is believed to be an important facilitator of familial communication of genetic risk information, empirical evidence of this association is lacking. We examined whether genetic knowledge was related to frequency of current familial communication about colorectal cancer and polyp (CRCP) risk, and future intention to share CRCP-related genomic test results with family members in a clinical sample of patients. We recruited 189 patients eligible for clinical CRCP sequencing to the eMERGE III FamilyTalk randomized controlled trial and surveyed them about genetic knowledge and familial communication at baseline. Participants were primarily Caucasian, 47% male, average age of 68 years, mostly well educated, and with high-income levels. Genetic knowledge was positively associated with future-intended familial communication of genetic information (odds ratio = 1.11, 95% confidence interval: 1.02-1.23), but not associated with current communication of CRC risk (ß = 0.01, p = .58). Greater current communication of CRC risk was associated with better family functioning (ß = 0.04, p = 8.2e-5). Participants' genetic knowledge in this study was minimally associated with their intended familial communication of genetic information. Although participants have good intentions of communication, family-level factors may hinder actual follow through of these intentions. Continued focus on improving proband's genetic knowledge coupled with interventions to overcome family-level barriers to communication may be needed to improve familial communication rates.

Perceptions of provider's epistemic authority in response to variant of uncertain significance-related recommendations.

Uncertain genetic information such as variants of uncertain significance (VUS) is often encountered by patients in clinical cancer genetic testing. Although healthcare providers facilitate patient's understanding of VUS-associated empirical risk and its medical implications, patients' understanding and perceptions of risk often differ and may be based on subjective evaluations such as their perception of provider's epistemic authority (EA). This study examines the hypothesis that individuals attribute greater EA to genetic counselors (GCs) (compared to gastrointestinal oncologists) and to providers who recommend more active VUS-related recommendations (compared to inactive). In a factorial experiment, 652 adult participants recruited on Amazon Mechanical Turk were block-randomized to read one of 10 different types of VUS-related scenarios in the context of colon cancer (5 recommendation types × 2 provider types). GCs were attributed higher EA than gastrointestinal oncologists (p = <.001). Active recommendations (comprehensive, check back, wrong) were attributed lower EA (M = 3.67, SD = 0.79) compared to the inactive (stand by, disregard) (M = 3.89, SD = 0.67) (p-value = <.001). The wrong recommendation was attributed lowest EA compared to the four correct recommendations (mean difference = -0.34, -0.45, -0.35, and -0.44, respectively; p = .002), which, when dropped from the analysis, showed no difference between the correct active and inactive recommendations (3.78 vs. 3.89, p = .095). The higher EA attributed to GCs is encouraging and possibly explained by increased public awareness of the genetic counseling profession. The lack of difference in EA attributed to various correct, yet incomplete forms of VUS-related recommendation indicates that individuals may be unaware of and thus completely rely on providers for complex medical topics like VUS. Communicating VUS-related uncertainty warrants caution and further research to elucidate best practices and outcomes.