Genetic epidemiology of ovarian cancer and prospects for polygenic risk prediction.

Epithelial ovarian cancer (EOC) is a heterogeneous disease with a major heritable component. The different histotypes of invasive disease - high grade serous, clear cell, endometrioid and mucinous - are associated with different underlying genetic susceptibility and epidemiological and lifestyle risk factors, all of which contribute to the different biology and clinical characteristics of each histotype. A combination of familial and population based sequencing studies, and genome wide association studies (GWAS) have identified a range of genetic susceptibility alleles for EOC comprising rare but highly penetrant genes (e.g. BRCA1, BRCA2) that are responsible for familial clustering of ovarian cancer cases; more moderate penetrance susceptibility genes (e.g. BRIP1, RAD51C/D, MSH6); and multiple common but low penetrance susceptibility alleles identified by GWAS. Identifying genetic risk alleles for ovarian cancer has had a significant impact on disease prevention strategies; for example it is now routine clinical practice for individuals with germline BRCA1 and BRCA2 mutations to undergo risk reducing salpingo-oophorectomy. Because ovarian cancers are commonly diagnosed at a late clinical stage when the prognosis is poor, the continued development of genetic risk prediction and prevention strategies will represent an important approach to reduce mortality due to ovarian cancer. Advances in genomics technologies that enable more high-throughput genetic testing, combined with research studies that identify additional EOC risk alleles will likely provide further opportunities to establish polygenic risk prediction approaches, based on combinations of rare high/moderate penetrance susceptibility genes and common, low penetrance susceptibility alleles. This article reviews the current literature describing the genetic and epidemiological components of ovarian cancer risk, and discusses both the opportunities and challenges in using this information for clinical risk prediction and prevention

Cancer Counseling of Low-Income Limited English Proficient Latina Women Using Medical Interpreters: Implications for Shared Decision-Making.

In cancer genetic counseling (CGC), communication across language and culture challenges the model of practice based on shared decision-making. To date, little research has examined the decision-making process of low-income, limited English proficiency (LEP) patients in CGC. This study identified communication patterns in CGC sessions with this population and assessed how these patterns facilitate or inhibit the decision-making process during the sessions. We analyzed 24 audio recordings of CGC sessions conducted in Spanish via telephone interpreters at two public hospitals. Patients were referred for risk of hereditary breast and ovarian cancer; all were offered genetic testing. Audio files were coded by two bilingual English-Spanish researchers and analyzed using conventional content analysis through an iterative process. The 24 sessions included 13 patients, 6 counselors, and 18 interpreters. Qualitative data analyses identified three key domains - Challenges Posed by Hypothetical Explanations, Misinterpretation by the Medical Interpreter, and Communication Facilitators - that reflect communication patterns and their impact on the counselor's ability to facilitate shared decision-making. Overall, we found an absence of patient participation in the decision-making process. Our data suggest that when counseling LEP Latina patients via medical interpreter, prioritizing information with direct utility for the patient and organizing information into short- and long-term goals may reduce information overload and improve comprehension for patient and interpreter. Further research is needed to test the proposed counseling strategies with this population and to assess how applicable our findings are to other populations

Cancer Counseling of Low-Income Limited English Proficient Latina Women Using Medical Interpreters: Implications for Shared Decision-Making.

In cancer genetic counseling (CGC), communication across language and culture challenges the model of practice based on shared decision-making. To date, little research has examined the decision-making process of low-income, limited English proficiency (LEP) patients in CGC. This study identified communication patterns in CGC sessions with this population and assessed how these patterns facilitate or inhibit the decision-making process during the sessions. We analyzed 24 audio recordings of CGC sessions conducted in Spanish via telephone interpreters at two public hospitals. Patients were referred for risk of hereditary breast and ovarian cancer; all were offered genetic testing. Audio files were coded by two bilingual English-Spanish researchers and analyzed using conventional content analysis through an iterative process. The 24 sessions included 13 patients, 6 counselors, and 18 interpreters. Qualitative data analyses identified three key domains - Challenges Posed by Hypothetical Explanations, Misinterpretation by the Medical Interpreter, and Communication Facilitators - that reflect communication patterns and their impact on the counselor's ability to facilitate shared decision-making. Overall, we found an absence of patient participation in the decision-making process. Our data suggest that when counseling LEP Latina patients via medical interpreter, prioritizing information with direct utility for the patient and organizing information into short- and long-term goals may reduce information overload and improve comprehension for patient and interpreter. Further research is needed to test the proposed counseling strategies with this population and to assess how applicable our findings are to other populations

Comparison of up-front cash cards and checks as incentives for participation in a clinician survey: a study within a trial.

BackgroundEvidence is needed regarding effective incentive strategies to increase clinician survey response rates. Cash cards are increasingly used as survey incentives; they are appealing because of their convenience and because in some cases their value can be reclaimed by investigators if not used. However, their effectiveness in clinician surveys is not known. In this study within the BRCA Founder OutReach (BFOR) study, a clinical trial of population-based BRCA1/2 mutation screening, we compared the use of upfront cash cards requiring email activation versus checks as clinician survey incentives.MethodsParticipants receiving BRCA1/2 testing in the BFOR study could elect to receive their results from their primary care provider (PCP, named by the patient) or from a geneticist associated with the study. In order to understand PCPs' knowledge, attitudes, experiences and willingness to disclose results we mailed paper surveys to the first 501 primary care providers (PCPs) in New York, Boston, Los Angeles and Philadelphia who were nominated by study participants to disclose their BRCA1/2 mutation results obtained through the study. We used alternating assignment stratified by city to assign the first 303 clinicians to receive a $50 up-front incentive as a cash card (N = 155) or check (N = 148). The cash card required PCPs to send an activation email in order to be used. We compared response rates by incentive type, adjusting for PCP characteristics and study site.ResultsIn unadjusted analyses, PCPs who received checks were more likely to respond to the survey than those who received cash cards (54.1% versus 41.9%, p = 0.046); this remained true when we adjusted for provider characteristics (OR for checks 1.61, 95% CI 1.01, 2.59). No other clinician characteristics had a statistically significant association with response rates in adjusted analyses. When we included an interaction term for incentive type and city, the favorable impact of checks on response rates was evident only in Los Angeles and Philadelphia.ConclusionsAn up-front cash card incentive requiring email activation may be less effective in eliciting clinician responses than up-front checks. However, the benefit of checks for clinician response rates may depend on clinicians' geographic location.Trial registrationClinicalTrials.gov ( NCT03351803 ), November 24, 2017

Comparison of up-front cash cards and checks as incentives for participation in a clinician survey: a study within a trial.

BackgroundEvidence is needed regarding effective incentive strategies to increase clinician survey response rates. Cash cards are increasingly used as survey incentives; they are appealing because of their convenience and because in some cases their value can be reclaimed by investigators if not used. However, their effectiveness in clinician surveys is not known. In this study within the BRCA Founder OutReach (BFOR) study, a clinical trial of population-based BRCA1/2 mutation screening, we compared the use of upfront cash cards requiring email activation versus checks as clinician survey incentives.MethodsParticipants receiving BRCA1/2 testing in the BFOR study could elect to receive their results from their primary care provider (PCP, named by the patient) or from a geneticist associated with the study. In order to understand PCPs' knowledge, attitudes, experiences and willingness to disclose results we mailed paper surveys to the first 501 primary care providers (PCPs) in New York, Boston, Los Angeles and Philadelphia who were nominated by study participants to disclose their BRCA1/2 mutation results obtained through the study. We used alternating assignment stratified by city to assign the first 303 clinicians to receive a $50 up-front incentive as a cash card (N = 155) or check (N = 148). The cash card required PCPs to send an activation email in order to be used. We compared response rates by incentive type, adjusting for PCP characteristics and study site.ResultsIn unadjusted analyses, PCPs who received checks were more likely to respond to the survey than those who received cash cards (54.1% versus 41.9%, p = 0.046); this remained true when we adjusted for provider characteristics (OR for checks 1.61, 95% CI 1.01, 2.59). No other clinician characteristics had a statistically significant association with response rates in adjusted analyses. When we included an interaction term for incentive type and city, the favorable impact of checks on response rates was evident only in Los Angeles and Philadelphia.ConclusionsAn up-front cash card incentive requiring email activation may be less effective in eliciting clinician responses than up-front checks. However, the benefit of checks for clinician response rates may depend on clinicians' geographic location.Trial registrationClinicalTrials.gov ( NCT03351803 ), November 24, 2017

The BRCA founder outreach study: Initial results of a digital health model.

2007 Background: NCCN now endorses BRCA founder mutation genetic testing (GT) via longitudinal studies in all Ashkenazi Jewish (AJ) individuals. The BRCA Founder OutReach (BFOR) study offers pre-GT online education with posttest engagement of primary care providers (PCPs). Methods: The study in 4 US cities enrolls those age > 25 with > 1 AJ grandparent. Participants enroll online with chatbot and video education, have GT at local centers, receive results from their PCP or BFOR staff, and are surveyed 12 weeks post disclosure and annually for 5 years. Univariate analyses and multivariable (MV) logistic regression models were used to evaluate characteristics associated with not completing GT, selecting PCP to disclose GT, and positive GT. Results: As of January 2020, 4754 participants consented (77.5% female, median age 51); 37.7% never previously considered GT. Cancer family histories (FHx) were 56.4% low risk (LR), 36.4% high risk (HR), and 7.2% had a familial mutation (FM). To date, 3658 participants (76.9%) completed and 677 (14.2%) did not complete GT; the remainder are pending. Only 34.8% of participants selected PCP to disclose GT, and 42.6% of PCPs agreed. Of the 124 mutation carriers (3.4%) identified, 60.5% had a FM. At the 12-week survey, 65.4% of mutation carriers planned to proceed with recommended screening or scheduled risk reducing surgery; 3.5% of those with negative GT and HR FHx reported further GT. Satisfaction was high (mean 9.58/10, SD 1.12) and unrelated to result (p>.05). Conclusions: A digital model for founder mutation testing engaged those with LR FHx and no prior experience with GT. Older participants were more likely to complete the study. Males were less likely to enroll but more likely to carry mutations. The majority of those who tested positive had a FM. A minority of results were disclosed by PCPs. Continued follow up is needed to determine long term outcomes. [Table: see text

Challenges and Opportunities in Engaging Primary Care Providers in BRCA Testing: Results from the BFOR Study

PurposeEngaging primary care providers (PCPs) in BRCA1/2 testing and results disclosure would increase testing access. The BRCA Founder OutReach (BFOR) study is a prospective study of BRCA1/2 founder mutation screening among individuals of Ashkenazi Jewish descent that sought to involve participants' PCPs in results disclosure. We used quantitative and qualitative methods to evaluate PCPs' perspectives, knowledge, and experience disclosing results in BFOR.MethodsAmong PCPs nominated by BFOR participants to disclose BRCA1/2 results, we assessed the proportion agreeing to disclose. To examine PCP's perspectives, knowledge, and willingness to disclose results, we surveyed 501 nominated PCPs. To examine PCPs' experiences disclosing results in BFOR, we surveyed 101 PCPs and conducted 10 semi-structured interviews.ResultsIn the BFOR study overall, PCPs agreed to disclose their patient's results 40.5% of the time. Two hundred thirty-four PCPs (46.7%) responded to the initial survey. Responding PCPs were more likely to agree to disclose patients' results than non-responders (57.3% vs. 28.6%, p<0.001). Among all respondents, most felt very (19.7%) or somewhat (39.1%) qualified to share results. Among PCPs declining to disclose, insufficient knowledge was the most common reason. In multivariable logistic regression, feeling qualified was the only variable significantly associated with agreeing to disclose results (OR 6.53, 95% CI 3.31, 12.88). In post-disclosure surveys (response rate=55%), PCPs reported largely positive experiences. Interview findings suggested that although PCPs valued the study-provided educational materials, they desired better integration of results and decision support into workflows.ConclusionBarriers exist to incorporating BRCA1/2 testing into primary care. Most PCPs declined to disclose their patients' BFOR results, although survey respondents were motivated and had positive disclosure experiences. PCP training and integrated decision support could be beneficial.Trial registrationClinicalTrials.gov (NCT03351803), November 24, 2017