Remotely Delivered Cancer Genetic Testing in the Making Genetic Testing Accessible (MAGENTA) Trial: A Randomized Clinical Trial.

Importance: Requiring personalized genetic counseling may introduce barriers to cancer risk assessment, but it is unknown whether omitting counseling could increase distress. Objective: To assess whether omitting pretest and/or posttest genetic counseling would increase distress during remote testing. Design, Setting, and Participants: Making Genetic Testing Accessible (MAGENTA) was a 4-arm, randomized noninferiority trial testing the effects of individualized pretest and/or posttest genetic counseling on participant distress 3 and 12 months posttest. Participants were recruited via social and traditional media, and enrollment occurred between April 27, 2017, and September 29, 2020. Participants were women aged 30 years or older, English-speaking, US residents, and had access to the internet and a health care professional. Previous cancer genetic testing or counseling was exclusionary. In the family history cohort, participants had a personal or family history of breast or ovarian cancer. In the familial pathogenic variant (PV) cohort, participants reported 1 biological relative with a PV in an actionable cancer susceptibility gene. Data analysis was performed between December 13, 2020, and May 31, 2023. Intervention: Participants completed baseline questionnaires, watched an educational video, and were randomized to 1 of 4 arms: the control arm with pretest and/or posttest genetic counseling, or 1 of 3 study arms without pretest and posttest counseling. Genetic counseling was provided by phone appointments and testing was done using home-delivered saliva kits. Main Outcomes and Measures: The primary outcome was participant distress measured by the Impact of Event Scale 3 months after receiving the results. Secondary outcomes included completion of testing, anxiety, depression, and decisional regret. Results: A total of 3839 women (median age, 44 years [range 22-91 years]), most of whom were non-Hispanic White and college educated, were randomized, 3125 in the family history and 714 in the familial PV cohorts. In the primary analysis in the family history cohort, all experimental arms were noninferior for distress at 3 months. There were no statistically significant differences in anxiety, depression, or decisional regret at 3 months. The highest completion rates were seen in the 2 arms without pretest counseling. Conclusions and Relevance: In the MAGENTA clinical trial, omitting individualized pretest counseling for all participants and posttest counseling for those without PV during remote genetic testing was not inferior with regard to posttest distress, providing an alternative care model for genetic risk assessment. Trial Registration: ClinicalTrials.gov Identifier: NCT02993068.

Ethical, legal, and social implications (ELSI) and challenges in the design of a randomized controlled trial to test the online return of cancer genetic research results to U.S. Black women.

BACKGROUND: A central challenge to precision medicine research efforts is the return of genetic research results in a manner that is effective, ethical, and efficient. Formal tests of alternate modalities are needed, particularly for racially marginalized populations that have historically been underserved in this context. METHODS: We are conducting a randomized controlled trial (RCT) to test scalable modalities for results return and to examine the clinical utility of returning genetic research results to a research cohort of Black women. The primary aim is to compare the efficacy of two communication modalities for results return: 1) a conventional modality that entails telephone disclosure by a Board-certified genetic counselor, and 2) an online self-guided modality that entails results return directly to participants, with optional genetic counselor follow-up via telephone. The trial is being conducted among participants in the Black Women's Health Study (BWHS), where targeted sequencing of 4000 participants was previously completed. RESULTS: Several ethical, legal, and social implications (ELSI) and challenges presented, which necessitated substantial revision of the original study protocol. Challenges included chain of custody, re-testing of research results in a CLIA lab, exclusion of VUS results, and digital literacy. Bioethical principles of autonomy, justice, non-maleficence, and beneficence were considered in the design of the study protocol. CONCLUSION: This study is uniquely situated to provide critical evidence on the effectiveness of alternative models for genetic results return and provide further insight into the factors influencing access and uptake of genetic information among U.S. Black women. CLINICALTRIALS: gov: NCT04407611.

Implementing digital systems to facilitate genetic testing for hereditary cancer syndromes: An observational study of 4 clinical workflows.

PURPOSE: National efforts have prioritized the identification of effective methods for increasing case ascertainment and delivery of evidence-based health care for individuals at elevated risk for hereditary cancers. METHODS: This study examined the uptake of genetic counseling and testing following the use of a digital cancer genetic risk assessment program implemented at 27 health care sites in 10 states using 1 of 4 clinical workflows: (1) traditional referral, (2) point-of-care scheduling, (3) point-of-care counseling/telegenetics, and (4) point-of-care testing. RESULTS: In 2019, 102,542 patients were screened and 33,113 (32%) were identified as at high risk and meeting National Comprehensive Cancer Network genetic testing criteria for hereditary breast and ovarian cancer, Lynch syndrome, or both. Among those identified at high risk, 5147 (16%) proceeded with genetic testing. Genetic counseling uptake was 11% among the sites with workflows that included seeing a genetic counselor before testing, with 88% of patients proceeding with genetic testing after counseling. Uptake of genetic testing across sites varied significantly by clinical workflow (6% referral, 10% point-of-care scheduling, 14% point-of-care counseling/telegenetics, and 35% point-of-care testing, P < .0001). CONCLUSION: Study findings highlight the potential heterogeneity of effectiveness attributable to different care delivery approaches for implementing digital hereditary cancer risk screening programs.

Internet-Based Germline Genetic Testing for Men With Metastatic Prostate Cancer.

PURPOSE: Germline mutations in DNA repair genes are present in approximately 10% of men with metastatic prostate cancer (mPC), and guidelines recommend genetic germline testing. Notable barriers exist, including access to genetic counseling, insurance coverage, and out-of-pocket costs. The GENTleMEN study was designed to determine the feasibility of an Internet-based, patient-driven germline genetic testing approach for men with mPC. PATIENTS AND METHODS: In this prospective cohort study, men with mPC provided informed consent via an Internet-based platform and completed a questionnaire including demographics and family cancer history. Supporting medical data were also collected. Genetic testing was performed using the Color Genomics 30-gene targeted panel of cancer predisposition genes on a mailed saliva sample. Men whose test results identified a germline pathogenic or likely pathogenic variant received results by phone or telehealth genetic counseling; other participants received results by email with an option for phone-based or telehealth genetic counseling. RESULTS: As of August 18, 2021, 816 eligible men were consented, of whom 68% (551) completed genetic testing, and 8.7% (48 of 551) were found to carry a pathogenic or likely pathogenic variant in a germline DNA repair gene: CHEK2 (17), BRCA2 (15), ATM (6), NBN1 (3), BRCA1 (2), PALB2 (2), PMS2 (2), and MSH6 (1). Participants were more likely to complete the testing process if they were non-Hispanic White, married, highly educated, or from a higher-income bracket. CONCLUSION: Here, we show the feasibility of delivering germline (inherited) genetic testing by a voluntary, patient-driven, Internet-based platform to men with mPC. Preliminary results show rates of germline DNA repair mutations, consistent with other cohorts. Although feasible for some, reduced steps for participation, more dedicated diverse outreach and participant support, and identification and addressing of additional barriers is needed to ensure equitable access and optimization.

Affordable Care Act state Medicaid expansion and human papillomavirus vaccination among adolescent and young adult US women: A national study.

OBJECTIVE: To ascertain the impact of Affordable Care Act (ACA) state Medicaid expansion on human papillomavirus (HPV) vaccination among both adolescent and young adult US women. DATA SOURCES: We used state-level data on ACA Medicaid expansion and individual-level data on US women aged 15-25 years living at or below 138% of the Federal Poverty Level (FPL) from the 2011-2017 waves of the National Survey of Family Growth (N = 2408). STUDY DESIGN: We conducted a quasi-experimental study examining the association between ACA state Medicaid expansion and HPV vaccination initiation among eligible adolescent and young adult US women. METHODS: We used linear probability modeling within a difference-in-differences approach, adjusting for individual- and state-level covariates. PRINCIPAL FINDINGS: Adjusting for individual- and state-level covariates, we found a negative association between Medicaid expansion and HPV vaccination among US women aged 15-25 years living in low-income households in the first year post-expansion (coefficient: -15.9 percentage points; 95% confidence interval [CI]: -30.1, -1.6 points). In contrast, we observed a positive association in the third year post-expansion (coefficient: 20.5 percentage points; 95% confidence interval [CI]: -1.8, 42.9 points). CONCLUSIONS: Medicaid expansion may have increased HPV vaccination among adolescent and young adult US women over time. Additional research is needed to identify the mechanisms and differential effects of Medicaid expansion on HPV vaccination among diverse subgroups of US women.

Barriers, interventions, and recommendations: Improving the genetic testing landscape.

Individual, provider, clinic, and societal level barriers have been shown to undermine the potential impact of genetic testing. The current approach in the primary care setting places an exorbitant burden on both providers and patients. Current literature provides insight into how to address barriers across multiple levels (patient, provider, clinic, system) and at multiple stages in the testing process (identification, referral, counseling, and testing) but interventions have had limited success. After outlining the current approach to genetic testing in the primary care setting, including the barriers that prevent genetic testing uptake and the methods proposed to address these issues, we recommend integrating genetic testing into routine medical care through population-based testing. Success in efforts to increase the uptake of genetic testing will not occur without significant changes to the way genetic services are delivered. These changes will not be instantaneous but are critical in moving this field forward to realize the potential for cancer risk genetic assessment to reduce cancer burden.

An Accessible Communication System for Population-Based Genetic Testing: Development and Usability Study.

BACKGROUND: Genetic testing uptake is low, despite the well-established connection between pathogenic variants in certain cancer-linked susceptibility genes and ovarian cancer risk. Given that most major insurers cover genetic testing for those with a family history suggestive of hereditary cancer, the issue may lie in access to genetic testing. Remotely accessible web-based communication systems may improve awareness, and uptake, of genetic testing services. OBJECTIVE: This study aims to present the development and formative evaluation of the multistep web-based communication system required to support the implementation of, and access to, genetic testing. METHODS: While designing the multistep web-based communication system, we considered various barriers and facilitators to genetic testing, guided by dimensions of accessibility. In addition to conducting usability testing, we performed ongoing assessments focusing on the function of the web-based system and participant response rates, with the goal of continuing to make modifications to the web-based communication system as it is in use. RESULTS: The combined approach of usability testing and expert user experience consultation resulted in several modifications to the multistep web-based communication system, including changes that related to imagery and content, web accessibility, and general organization of the web-based system. All recommendations were made with the goal of improving the overall accessibility of the web-based communication system. CONCLUSIONS: A multistep web-based communication system appears to be an effective way to address many potential barriers to access, which may otherwise make genetic testing difficult for at-risk individuals to participate in. Importantly, some dimensions of access were easy to assess before study recruitment, but other aspects of the communication system required ongoing assessment during the implementation process of the Making Genetic Testing Accessible study.

Using Social Media to Facilitate Communication About Women's Testing: Tool Validation Study.

BACKGROUND: Strong participant recruitment practices are critical to public health research but are difficult to achieve. Traditional recruitment practices are often time consuming, costly, and fail to adequately target difficult-to-reach populations. Social media platforms such as Facebook are well-positioned to address this area of need, enabling researchers to leverage existing social networks and deliver targeted information. The MAGENTA (Making Genetic Testing Accessible) study aimed to improve the availability of genetic testing for hereditary cancer susceptibility in at-risk individuals through the use of a web-based communication system along with social media advertisements to improve reach. OBJECTIVE: This paper is aimed to evaluate the effectiveness of Facebook as an outreach tool for targeting women aged ≥30 years for recruitment in the MAGENTA study. METHODS: We designed and implemented paid and unpaid social media posts with ongoing assessment as a primary means of research participant recruitment in collaboration with patient advocates. Facebook analytics were used to assess the effectiveness of paid and unpaid outreach efforts. RESULTS: Over the course of the reported recruitment period, Facebook materials had a reach of 407,769 people and 57,248 (14.04%) instances of engagement, indicating that approximately 14.04% of people who saw information about the study on Facebook engaged with the content. Paid advertisements had a total reach of 373,682. Among those reached, just <15% (54,117/373,682, 14.48%) engaged with the page content. Unpaid posts published on the MAGENTA Facebook page resulted in a total of 34,087 reach and 3131 instances of engagement, indicating that around 9.19% (3131/34,087) of people who saw unpaid posts engaged. Women aged ≥65 years reported the best response rate, with approximately 43.95% (15,124/34,410) of reaches translating to engagement. Among the participants who completed the eligibility questionnaire, 27.44% (3837/13,983) had heard about the study through social media or another webpage. CONCLUSIONS: Facebook is a useful way of enhancing clinical trial recruitment of women aged ≥30 years who have a potentially increased risk for ovarian cancer by promoting news stories over social media, collaborating with patient advocacy groups, and running paid and unpaid campaigns. TRIAL REGISTRATION: ClinicalTrials.gov NCT02993068; https://clinicaltrials.gov/ct2/show/NCT02993068.

Socioeconomic Status and Interest in Genetic Testing in a US-Based Sample.

Cancer is a significant burden, particularly to individuals of low socioeconomic status (SES). Genetic testing can provide information about an individual's risk of developing cancer and guide future screening and preventative services. However, there are significant financial barriers, particularly for individuals of low SES. This study used the Early Detection of Genetic Risk (EDGE) Study's patient baseline survey (n = 2329) to evaluate the relationship between socioeconomic status and interest in pursuing hereditary cancer genetic testing. Analysis was completed for two interest outcomes-overall interest in genetic testing and interest in genetic testing if the test were free or low cost. Many demographic and SES variables were predictors for interest in genetic testing, including education, income, and MacArthur Subjective Social Scale (SSS). After controlling for the healthcare system, age, and gender, having a higher education level and a higher household income were associated with greater general interest. Lower SSS was associated with greater interest in genetic testing if the test was free or low cost. If genetic testing is the future of preventative medicine, more work needs to be performed to make this option accessible to low-SES groups and to ensure that those services are used by the most underserved populations.

Learning from and Leveraging Multi-Level Changes in Responses to the COVID 19 Pandemic to Facilitate Breast Cancer Prevention Efforts.

The coronavirus pandemic (COVID-19) has had multilevel effects on non-COVID-19 health and health care, including deferral of routine cancer prevention and screening and delays in surgical and other procedures. Health and health care use has also been affected by pandemic-related loss of employer-based health insurance, food and housing disruptions, and heightened stress, sleep disruptions and social isolation. These disruptions are projected to contribute to excess non-COVID-19 deaths over the coming decades. At the same time municipalities, health systems and individuals are making changes in response to the pandemic, including modifications in the environmental to promote health, implementation of telehealth platforms, and shifts towards greater self-care and using remote platforms to maintain social connections. We used a multi-level biopsychosocial model to examine the available literature on the relationship between COVID-19-related changes and breast cancer prevention to identify current gaps in knowledge and identify potential opportunities for future research. We found that COVID-19 has impacted several aspects of social and economic life, through a variety of mechanisms, including unemployment, changes in health care delivery, changes in eating and activity, and changes in mental health. Some of these changes should be reduced, while others should be explored and enhanced.

The Role of Stress in Breast Cancer Incidence: Risk Factors, Interventions, and Directions for the Future.

Stress is a common belief among breast cancer patients and the public to explain variation in breast cancer incidence. Epidemiological studies interrogating the relationship between stress and cancer have reported mixed results. The impact of the topic and the lack of consensus has sparked this review of the literature to investigate gaps in knowledge and identify areas of research. We first present a brief summary of the biopsychosocial model generally used to conduct research on stress. We then divide the overview of the literature into areas of research focus. These include the role of distressing life events in breast cancer incidence, the role of adverse childhood events in later breast cancer incidence, the importance of race and socioeconomic status (SES) as social determinants of breast cancer incidence, and the specific role of chronic stress in relation to breast cancer. For each topic, we discuss the potential of stress as a risk factor and possible intervention strategies that could reduce the effects of stress. We then identify further research questions to be probed to fill the gaps in knowledge. We conclude with a discussion of future research directions for stress research as it relates to breast cancer incidence.

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.

Risk Ladder, Table, or Bulleted List? Identifying Formats That Effectively Communicate Personalized Risk and Risk Reduction Information for Multiple Diseases.

BACKGROUND: Personalized medicine may increase the amount of probabilistic information patients encounter. Little guidance exists about communicating risk for multiple diseases simultaneously or about communicating how changes in risk factors affect risk (hereafter "risk reduction"). PURPOSE: To determine how to communicate personalized risk and risk reduction information for up to 5 diseases associated with insufficient physical activity in a way laypeople can understand and that increases intentions. METHODS: We recruited 500 participants with <150 min weekly of physical activity from community settings. Participants completed risk assessments for diabetes, heart disease, stroke, colon cancer, and breast cancer (women only) on a smartphone. Then, they were randomly assigned to view personalized risk and risk reduction information organized as a bulleted list, a simplified table, or a specialized vertical bar graph ("risk ladder"). Last, they completed a questionnaire assessing outcomes. Personalized risk and risk reduction information was presented as categories (e.g., "very low"). Our analytic sample (N = 372) included 41.3% individuals from underrepresented racial/ethnic backgrounds, 15.9% with vocational-technical training or less, 84.7% women, 43.8% aged 50 to 64 y, and 71.8% who were overweight/obese. RESULTS: Analyses of covariance with post hoc comparisons showed that the risk ladder elicited higher gist comprehension than the bulleted list (P = 0.01). There were no significant main effects on verbatim comprehension or physical activity intentions and no moderation by sex, race/ethnicity, education, numeracy, or graph literacy (P > 0.05). Sequential mediation analyses revealed a small beneficial indirect effect of risk ladder versus list on intentions through gist comprehension and then through perceived risk (bIndirectEffect = 0.02, 95% confidence interval: 0.00, 0.04). CONCLUSION: Risk ladders can communicate the gist meaning of multiple pieces of risk information to individuals from many sociodemographic backgrounds and with varying levels of facility with numbers and graphs.

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.

Design of a study to implement population-based risk assessment for hereditary cancer genetic testing in primary care.

Identifying patients with high genetic risk for cancer has important clinical ramifications, but hereditary cancer risk is often not identified because of testing barriers at both the provider and patient level. It is unknown how to best implement appropriate genetic testing and follow-up care into an operating primary care clinic. Implementation studies to date have been conducted in high resourced facilities under optimal conditions, often not at the clinic level. This study aims to compare and evaluate two population-wide engagement strategies for identifying members of a primary care clinic's population with a family or personal history of cancer and offering high-risk individuals genetic testing for cancer susceptibility mutations. The two engagement strategies are: 1) point of care screening (POC), conducted when a patient is scheduled for an appointment and 2) direct patient engagement (DPE), where outreach provides the patient an opportunity to complete screening online on their own time. The study will identify changes, problems, and inefficiencies in clinical flow during and after the implementation of risk assessment and genomic testing for cancer risk across primary care clinics. It will also evaluate the effects of the two engagement strategies on patient, provider, and clinic leader outcomes, including perceptions of benefits, harms, and satisfaction with the engagement strategy and process of cancer risk assessment and genetic testing, across gender, racial/ethnic, socioeconomic, and genetic literacy divides. Finally, the study will evaluate the cost-effectiveness and budget impact of each engagement strategy.

Sexual Orientation Identity Disparities in Mammography Among White, Black, and Latina U.S. Women.

Purpose: Our goal was to examine sexual orientation identity disparities in mammography in relationship to race/ethnicity among U.S. women. Methods: Using nationally representative 2013-2017 National Health Interview Survey data, we used multivariable logistic regression to estimate the odds of receiving a mammogram in the past year in relationship to sexual orientation identity among White, Black, and Latina U.S. women 40-75 years of age (N = 45,031) separately, adjusting for demographic factors. We also assessed whether socioeconomic and health care factors attenuated sexual orientation identity disparities in mammography across racial/ethnic groups. Results: Among White women, bisexual women had significantly lower adjusted odds of mammography compared to heterosexual women (odds ratio = 0.70, 95% confidence interval: 0.50-0.99). Among Black women, the adjusted odds of mammography were significantly higher among bisexual women relative to heterosexual women (2.53, 1.08-5.92). Black lesbian women appeared to have lower adjusted odds of mammography compared to their heterosexual counterparts; however, this difference was not statistically significant (0.80, 0.46-1.38). Similarly, among Latina women, lesbian women also seemed to have lower adjusted odds of mammography relative to heterosexual women, but this disparity was also not statistically significant (0.64, 0.37-1.13). Adding socioeconomic factors completely attenuated the disparity between White bisexual and heterosexual women (0.76, 0.52-1.10). Conclusions: Sexual orientation identity disparities in receiving a mammogram in the past year differed in relationship to race/ethnicity among White, Black, and Latina U.S. women. Additional research with larger samples of Black and Latina lesbian and bisexual women is needed to more accurately estimate and explain observed differences.

Perceptions of risk and reward in BRCA1 and BRCA2 mutation carriers choosing salpingectomy for ovarian cancer prevention.

Salpingectomy with interval oophorectomy has gained traction as an ovarian cancer prevention strategy, but is not currently recommended for high risk women. Nevertheless, some choose this approach. We aimed to understand risk perception and plans for oophorectomy in BRCA1 and BRCA2 (BRCA) mutation carriers choosing salpingectomy for ovarian cancer prevention. This was a longitudinal survey study of BRCA mutation carriers who underwent bilateral salpingectomy to reduce ovarian cancer risk. An initial written questionnaire and telephone interview was followed by annual phone interviews. 22 women with BRCA mutations were enrolled. Median follow-up was three years. The median age at salpingectomy was 39.5 years (range 27-49). Perceived lifetime ovarian cancer risk decreased by half after salpingectomy (median risk reduction 25%, range 0-40%). At final follow-up, five (22.7%) had undergone oophorectomy and five women (22.7%) were not planning to undergo completion oophorectomy. BRCA mutation carriers who had salpingectomy after the recommended age of prophylactic surgery (vs. before the recommended age) were less likely to plan for future oophorectomy (28.6% vs. 66.7%, p = 0.037). All women were satisfied with their decision to undergo salpingectomy with eighteen (81.8%) expressing decreased cancer-related worry. There were no diagnoses of ovarian cancer during our study period. In conclusion, most BRCA mutation carriers undergoing risk-reducing salpingectomy are satisfied with their decision and have lower risk perception after salpingectomy, though some older mutation carriers did not plan on future oophorectomy. Salpingectomy with delayed oophorectomy in BRCA mutation carriers remains investigational and should preferably be performed within a clinical trial to prevent introduction of an innovation before safety has been proven.

Exploring relatives' perceptions of participation, ethics, and communication in a patient-driven study for hereditary cancer variant reclassification.

Effective communication of genetic information within families depends on several factors. Few studies explore intra-familial communication of variant of uncertain significance (VUS) results or active collaboration between family members to classify VUS. Our qualitative study aimed to describe the experiences of individuals asked by family members to participate in the FindMyVariant study, a patient-driven family study which aimed to reclassify a clinically identified familial VUS in a hereditary cancer gene. We collected feedback from 56 individuals from 21 different families through phone interviews and written correspondence, transcribed the interviews, and performed thematic analysis on all text. We describe themes from three main topics: participation, ethical considerations, and study impacts. Participation in the FindMyVariant study, defined as returning a sample for targeted genotyping, was motivated by convenience and a desire to help the family, oneself, and science. Relatives were generally responsive to invitations to participate in FindMyVariant from another family member. Those who declined to participate did so due to concerns about research program confidentiality rather than family dynamics. No major ethical issues arose in response to the patient-driven study structure, and no major changes in stress and anxiety, medical care, or behavior occurred. Participation in patient-driven familial VUS classification studies has a neutral or positive impact on family health communication. While it is important to design studies to minimize familial coercion, intra-familial confidentiality breaches, and misinterpretation of genetic results, these were not major concerns among relatives in this study. Clinicians and laboratories may consider encouraging familial communication about genetic variants using family members as liaisons.