Risk For Hereditary Breast And Ovarian Cancer Research Articles

Targeted sequencing for hereditary breast and ovarian cancer in BRCA1/2-negative families reveals complex genetic architecture and phenocopies

Approximately 20% of breast cancer cases are attributed to increased family risk; yet variation in BRCA1/2 can only explain 20-25% of cases. Historically, only single gene or single variant testing were common in at-risk family members, and further sequencing studies were rarely offered after negative results. In this study, we applied an efficient and inexpensive targeted sequencing approach to provide molecular diagnoses in 245 human samples representing 134 BRCA mutation negative (BRCAX) hereditary breast and ovarian cancer (HBOC) families recruited from 1973-2019 by Dr. Henry Lynch. Sequencing identified 391 variants, which were functionally annotated and ranked based on their predicted clinical impact. Known pathogenic CHEK2 breast cancer variants were identified in five BRCAX families in this study. While BRCAX was an inclusion criterion for this study, we still identified a pathogenic BRCA2 variant (p.Met192ValfsTer13) in one family. A portion of BRCAX families could be explained by other hereditary cancer syndromes that increase HBOC risk: Li-Fraumeni Syndrome (gene: TP53) and Lynch Syndrome (gene: MSH6). Interestingly, many families carried additional Variants of Undetermined Significance (VOUSs) that may further modify phenotypes of syndromic family members. Ten families carried more than one potential VOUS suggesting the presence of complex multi-variant families. Overall, nine BRCAX HBOC families in our study may be explained by known likely-pathogenic/pathogenic variants, and six families carried potential VOUSs, which require further functional testing. To address this, we developed a functional assay where we successfully re-classified one family’s PMS2 VOUS as benign.

Abstract PO4-09-08: Perceptions and Experiences of Black Women on Family History Sharing and Genetic Testing for Hereditary Breast and Ovarian Cancer

Abstract Black women experience significant disparities in morbidity and mortality related to hereditary breast and ovarian cancer (HBOC). Early identification of women with HBOC is essential for proactive screening and timely diagnosis. However, evidence suggests that Black women receive genetic testing for HBOC at lower rates than their White counterparts. We conducted in-depth qualitative interviews with 107 Black women with a personal or family history of breast or ovarian cancer, to understand their perceptions of their familial risk of HBOC and interest in genetic testing. In phase 1 of this study, participants were recruited from the networks of patient support organizations and historically Black sororities representing mostly highly educated and well insured patients. In phase 2, participants were recruited from a family medicine safety net clinic in Jacksonville, FL for socioeconomic diversity. Participants in both cohorts frequently expressed a lack of awareness about their family cancer history and identified many barriers to family disclosure of a cancer diagnosis. These include a culture of silence around medical issues and a belief that personal difficulties should be kept to oneself. Practical and cultural barriers to family history sharing were magnified among those with lower socioeconomic status. Many participants in both cohorts indicated a strong desire to understand their own risk of HBOC. They also expressed interested in genetic testing to proactively mitigate risk to themselves and future generations. Understanding of the potential relevance of HBOC testing to one’s personal health and post-test actionability was variable across both groups, although perceptions of genetic testing were generally favorable. These findings suggest that culturally tailored educational materials and alternative clinical modalities to collect family health history may be beneficial to improve timely identification of Black women who meet NCCN Guidelines for HBOC testing. Specifically, greater attention should be given to addressing barriers that led to underestimation of HBOC risk among patients experiencing disparities driven by adverse social determinants of health. Citation Format: Kirsten Riggan, Jane Yap, Ewan Cobran, Michele Halyard, Sarah James, Marion Kelly, Daphne Phillips, Megan Allyse. Perceptions and Experiences of Black Women on Family History Sharing and Genetic Testing for Hereditary Breast and Ovarian Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-09-08.

Young Women's Perspectives on Being Screened for Hereditary Breast and Ovarian Cancer Risk During Routine Primary Care

PurposeThe U.S. Preventive Services Task Force recommends screening women to identify individuals eligible for genetic counseling based on a priori hereditary breast and ovarian cancer syndrome (HBOC) risk (i.e., risk assessment). However, risk assessment has not been widely integrated into primary care. This qualitative study explored young women's views on implementing routine HBOC risk assessment with a focus on equity and patient-centeredness. MethodsWe conducted group discussions with young women (aged 21–40 years) receiving care in an integrated health care system. Discussion groups occurred in two phases and used a modified deliberative approach that included a didactic component and prioritized developing consensus. Twenty women participated in one of three initial small group discussions (phase one). All 20 were invited to participate in a subsequent large group discussion (phase two), and 15 of them attended. FindingsKey themes and recommendations were as follows. Risk assessment should be accessible, contextualized, and destigmatized to encourage participation and reduce anxiety, particularly for women who do not know their family history. Providers conducting risk assessments must be equipped to address women's informational needs, relieve emotionality, and plan next steps after positive screens. Finally, to minimize differential screening uptake, health care systems must prioritize equity in program design and contribute to external educational and outreach efforts. ConclusionYoung women see pragmatic opportunities for health systems to optimize HBOC screening implementation.

Talking about Familial Breast and Ovarian Cancer Risk-Evaluation of a Psychosocial Training Module for Gynecologists in Germany.

Primary care gynecologists are increasingly integrated into the care of patients with hereditary breast and ovarian cancer (HBOC) risks. These physicians should not only have basic genetic knowledge; they should also feel able to sensitively address an increased HBOC risk and deal with emotional, stressful situations in this context. Our project aimed at developing a training module, 'iKNOWgynetics', addressing psychosocial challenges in the context of HBOC care for primary care gynecologists. We developed the psychosocial training module in three phases: first, we conducted an online survey with n = 35 women with a family history of breast or ovarian cancer to assess patients' experiences and needs. Second, based on the results of the needs assessment, we developed the training module. Third, we evaluated the training by assessing physicians' (n = 109) self-efficacy with regard to communication skills in the context of HBOC before and after the training. In the needs assessment, seven psychosocial themes emerged. These themes, complementing a review of the literature, informed the training curriculum. The training was divided into two parts: (1) communicating with women before genetic testing and (2) care co-management for women with HBOC after genetic testing. After the training, participants reported a significant increase in self-efficacy in three domains: communicating empathetically, educating patients in a comprehensible way and dealing with emotionally challenging situations. Our results highlight the relevance of psychosocial issues for patients with HBOC. A genetic literacy training module that integrates aspects of psychosocial care increases physicians' confidence in dealing with emotionally challenging situations before and after their patients' genetic testing. Thus, such trainings may improve the care of women with hereditary cancer risks.

Abstract A067: Perceptions and experiences of Black women on hereditary breast and ovarian cancer genetic testing

Abstract Black women experience significant disparities in morbidity and mortality related to hereditary breast and ovarian cancer (HBOC). Early identification of women with HBOC is essential for proactive screening and timely diagnosis but evidence suggests that Black women receive genetic testing for HBOC at lower rates than their White counterparts. To understand Black women’s perspectives on HBOC genetic testing and potential factors influencing this decision, we conducted in-depth qualitative interviews with 107 Black women with a personal or family history of breast or ovarian cancer. Participants were recruited via the networks of patient support organizations and sororities as well as at a family medicine safety net clinic in Jacksonville, FL. Participants frequently expressed a lack of awareness about their family cancer history; many cancer patients stated that they only became aware of extensive family history upon their own diagnosis. Lack of family history sharing was attributed to a culture of silence around medical issues and a desire to protect family members from difficult information. However, most participants indicated a strong desire to understand their own risk of HBOC and were interested in genetic testing. Participants with a personal diagnosis were motivated to undergo HBOC genetic testing to reduce the risk for future generations. Clinical experiences with the offer of HBOC genetic testing were variable, with a few expressing that they had to make repeated inquiries from a provider to understand the relevance of the test to their own health. These findings suggest that investigation into alternative clinical modalities to collect family health history may be beneficial to identify Black women who meet NCCN Guidelines for HBOC testing. In contrast to the literature suggesting hesitancy for HBOC genetic testing, many participants perceived genetic results as having a positive impact for their medical decision-making and family's health. The development of patient materials and provider education on cultural and social factors that influence the uptake of HBOC genetic testing is also needed. Citation Format: Kirsten A. Riggan, Michele Halyard, Sarah E. James, Marion Kelly, Daphne Phillips, Megan A. Allyse. Perceptions and experiences of Black women on hereditary breast and ovarian cancer genetic testing [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A067.

Prevalence of germline mutations in women with breast and/or ovarian cancer in a tertiary care center in Pune, India

In India, the incidence of breast cancer accounted for 1,78,361 cases, whereas ovarian cancer accounts for 45,701 cases, according to Globocan Report 2020. These cancers are known to have a hereditary basis, and >10% of them are associated with pathogenic BRCA1 and BRCA2 mutations. The prevalence of BRCA1 and BRCA2 varies across various Indian studies and is reported to be 2.9–28%. However, gene mutations other than BRCA1 and BRCA2 which are shown to increase the risk of hereditary breast and ovarian cancer (HBOC) are underreported. Objectives: The objective of this study was to estimate the prevalence of deleterious germline mutations among women with breast and/or ovarian cancer. Material and Methods: A cross-sectional study was conducted in the department of oncology at a super specialty hospital. Patients were enrolled based on the current National Comprehensive Cancer Network guidelines for genetic risk and evaluation of HBOC. Demographic and clinical information was extracted from the electronic medical records of the hospitals from 2018 to 2021. Next-generation sequencing (NGS) was performed on the extracted DNA using a custom capture kit and classified based on the American College of Medical Genetics. Results: A total of 94 patients suspected of having HBOC were examined for deleterious germline mutations. The median age of the patient was 46 years (range: 38–57 years). Breast and ovarian cancer patients constituted 64.9% and 35.1%, respectively. The overall mutation detection rate was 25.5%. The positive mutation detection rate was 26.2% and 24.2% in breast and ovarian cancer, respectively, whereas the variant of uncertain significance rate was 18.03% and 24.2%, respectively. Among the pathogenic mutations, BRCA1 was the most common mutation in women with breast cancer (81.3%). In ovarian cancer, it was 50%. BRCA2 mutation was more prevalent in ovarian cancer (50%). Conclusion: Our study reports a higher prevalence of germline BRCA1 and BRCA2 mutations in breast and ovarian cancer as compared to other studies. Genetic testing can be offered to high-risk women regardless of family history. This will be useful during diagnosis and help physicians in planning subsequent treatment.

Addressing disparities in the uptake of genetic counseling and testing in African American women; rationale, design and methods

BackgroundGenetic counseling and testing (GCT) informs risk reduction and management strategies in women at risk for carrying a pathogenic variation in the BRCA1 or BRCA2 (BRCA1/2) genes. African American (hereinafter referred to as Black) women are less likely to receive GCT services for hereditary breast and ovarian cancer (HBOC). The objective of this work was to examine existing literature regarding successful culturally tailored GCT interventions for Black women and to describe the rationale and protocol for a randomized feasibility trial to test the efficacy of a culturally tailored GCT intervention. Methods/designThe For Our Health (FOH) study is a two-arm randomized control trial designed to test the efficacy of a video intervention to promote the uptake of GCT among Black women with a high risk of HBOC. The culturally tailored video intervention targets key beliefs, knowledge gaps, misconceptions, and key anticipated emotions relevant for GCT. After completing the baseline survey, 50 women at risk of HBOC will be randomized (1:1) to one of two trial arms: a YouTube video intervention or a publicly available fact sheet. Final assessments will immediately follow receipt of either video or fact sheet. ConclusionFew studies have tested interventions to improve GCT uptake among Black women. The FOH trial will fill an important scientific gap in knowledge regarding strategies to reduce disparities in GCT among Black women at risk of HBOC.

Advancing health equity: A qualitative study assessing barriers and facilitators of implementing hereditary breast and ovarian cancer risk screening tools in community-based organizations.

Genetic counseling and testing (GCT) inform cancer management for persons at risk for hereditary breast and ovarian cancer (HBOC). Community-based organizations (CBOs) may play a role in identifying at-risk Latinx individuals to connect them to GCT but data are lacking. Two academic centers and their four CBO partners planned to implement a validated questionnaire for HBOC risk screening ("HBOC risk screening tool"). This study aimed to assess CBO's preferences for HBOC risk screening tools, as well as the barriers and facilitators anticipated for future implementation. Pre-implementation focus groups were conducted with CBO's staff. Discussions centered on current practices to identify and refer at-risk patients. During the discussion, staff were asked to select one out of five validated HBOC risk screening tools to implement and to discuss anticipated barriers/facilitators for implementation. The four focus groups were coded and qualitative analyzed following the Consolidated Framework for Implementation Research (CFIR) and Health Equity domains. All CBOs chose the Family History Screen 7 (FHS-7). Participants (N = 35) highlighted how the FHS-7 was easy to adapt to better fit the target population and changing guidelines. They had positive attitudes toward implementing the screening tool, stressed how the culture of the organization positioned them to reach the target population, and noted barriers in different CFIR domains (e.g., low knowledge about HBOC and GCT referrals; scarce available resources). Participants pointed to barriers related to health equity domains including limited access to GCT and follow-up care for uninsured and underinsured populations, challenges obtaining accurate family history, and immigration-related barriers. CBOs highlighted the importance of partnering with other stakeholders to overcome barriers. Findings emphasize the need to develop multi-level implementation strategies to overcome barriers and leverage facilitators. This study can inform the development of implementation toolkits for CBOs to implement HBOC screening tools to advance health equity.

Understanding cancer genetic risk assessment motivations in a remote tailored risk communication and navigation intervention randomized controlled trial

ABSTRACT Background National guidelines recommend cancer genetic risk assessment (CGRA) (i.e. genetic counseling prior to genetic testing) for women at increased risk for hereditary breast and ovarian cancer (HBOC). Less than one-half of eligible women obtain CGRA, leaving thousands of women and their family members without access to potentially life-saving cancer prevention interventions. Purpose The Genetic Risk Assessment for Cancer Education and Empowerment Project (GRACE) addressed this translational gap, testing the efficacy of a tailored counseling and navigation (TCN) intervention vs. a targeted print brochure vs. usual care on CGRA intentions. Selected behavioral variables were theorized to mediate CGRA intentions. Methods Breast and ovarian cancer survivors meeting criteria for guideline-based CGRA were recruited from three state cancer registries (N = 654), completed a baseline survey, and were randomized. TCN and targeted print arms received the brochure; TCN also participated in a tailored, telephone-based decision coaching and navigation session grounded in the Extended Parallel Process Model and Ottawa Decision Support Framework. Participants completed a one-month assessment. Logistic regression was used to compare the rate of CGRA intentions. CGRA intentions and theorized mediator scores (continuous level variables) were calculated using mixed model analysis. Results CGRA intentions increased for TCN (53.2%) vs. targeted print (26.7%) (OR = 3.129; 95% CI: 2.028, 4.827, p < .0001) and TCN vs. usual care (23.1%) (OR = 3.778, CI: 2.422, 5.894, p < .0001). Perceived risk (p = 0.023) and self-efficacy (p = 0.035) mediated CGRA intentions in TCN. Conclusions Improvements in CGRA intentions and theorized mediators support the use of a tailored communication intervention among women at increased HBOC risk. (Clinicaltrials.gov: NCT03326713.) Trial registration: ClinicalTrials.gov identifier: NCT03326713.

Cost-Effectiveness of BRCA 1/2 Genetic Test and Preventive Strategies: Using Real-World Data From an Upper-Middle Income Country.

Although BRCA1/2 genetic testing in developed countries is part of the reality for high-risk patients for hereditary breast and ovarian cancer (HBOC), the same is not true for upper-middle-income countries. For that reason, this study aimed to evaluate whether the BRCA1/2 genetic test and preventive strategies for women at high risk for HBOC are cost-effective compared to not performing these strategies in an upper-middle-income country. Adopting a payer perspective, a Markov model with a time horizon of 70 years was built to delineate the health states for a cohort of healthy women aged 30 years that fulfilled the BRCA1/2 testing criteria according to the guidelines. Transition probabilities were calculated based on real-world data of women tested for BRCA1/2 germline mutations in a cancer reference hospital from 2011 to 2020. We analyzed 275 BRCA mutated index cases and 356 BRCA mutation carriers that were first- or second-degree relatives of the patients. Costs were based on the Brazilian public health system reimbursement values. Health state utilities were retrieved from literature. The BRCA1/2 genetic test and preventive strategies result in more quality-adjusted life years (QALYs) and costs with an incremental cost-effectiveness ratio of R$ 11,900.31 (U$ 5,504.31)/QALY. This result can represent a strong argument in favor of implementing genetic testing strategies for high-risk women even in countries with upper-middle income, considering not only the cancer prevention possibilities associated with the genetic testing but also its cost-effectiveness to the health system. These strategies are cost-effective, considering a willingness-to-pay threshold of R$ 25,000 (U$ 11,563.37)/QALY, indicating that the government should consider offering them for women at high risk for HBOC. The results were robust in deterministic and probabilistic sensitivity analyses.

Understanding Cancer Genetic Risk Assessment Intentions in a Tailored Risk Communication Intervention Randomized Controlled Trial

Background: Pathogenic variants in cancer predisposition genes increase second, hereditary cancer risk among women with breast and/or ovarian cancer, and primary cancers in their relatives. National guidelines recommend cancer genetic risk assessment (CGRA) (genetic counseling and/or genetic testing) for women at increased hereditary breast and ovarian cancer (HBOC) risk. Yet, less than half of high risk women, including rural dwellers and racial minorities have accessed CGRA. Purpose: The Genetic Risk Assessment for Cancer Education and Empowerment Project (GRACE), a superiority trial, addressed this translational gap, testing the efficacy of a targeted print brochure (TP) vs tailored counseling and navigation (TCN) vs usual care (UC) on CGRA intentions. TCN targeted behavioral variables theorized to mediate CGRA intentions. We believe GRACE is the first study of its kind promoting guideline-based CGRA to women at increased HBOC risk. Methods: CGRA-eligible women were recruited from three state cancer registries (N=641), completed a baseline survey, and randomized to TCN, TP or UC. TP and TCN received the mailed educational brochure. TCN also engaged in a telephone-based decision coaching and navigation session using motivational interviewing and tailored materials based on the Extended Parallel Process Model and Health Action Process Approach. Participants completed a follow-up survey at one month. Results: TCN improved CGRA intentions compared to TP (0.64, p&amp;lt;0.001, CI 0.32, 0.97) and UC (0.69, p&amp;lt;0.001, CI 0.37, 1.02). Theoretical targets, perceived risk (0.77, p=0.02, CI 0.11, 1.44) and self-efficacy (0.67, p=0.04, CI 0.05, 1.28) mediated CGRA intentions in TCN. Stratification showed increases in CGRA intentions for TCN vs TP among non-Hispanic Whites, Hispanics, urban dwellers, and women with low health literacy and no family history of breast and/or ovarian cancer (FBOC). In TCN, perceived self-efficacy improved in women with no FBOC. Conclusions: Improvements in CGRA intentions and theorized mediators support use of tailored risk communication interventions in Hispanics and women with low health literacy and no FBOC. Further tailoring may improve CGRA intentions in Blacks, other minorities, rural dwellers, and women with high health literacy and FBOC.

OP012: Perceptions of breast and ovarian cancer risk and genetic testing among Non-Hispanic Black women

Non-Hispanic Black (NHB) women experience health disparities from familial and hereditary breast and ovarian cancer (HBOC) compared to other racial and ethnic groups, including 40% higher mortality from breast cancer compared to non-Hispanic White women. One potential factor in these disparities includes lower uptake of HBOC genetic testing. This study explores potential factors for the lower use of HBOC genetic testing in NHB women and their families. Understanding these factors is critical to improving uptake of HBOC testing in the NHB community and improving HBOC racial and ethnic health disparities. A national sample of NHB women with personal or family history of HBOC were recruited through patient support organizations, historically Black colleges and university sororities, professional organizations for women of African descent, and snowball sampling. Participants were interviewed using an interview guide developed by content experts and a community advisory board. Interviews were audio recorded and transcribed verbatim. Interview transcripts were qualitatively analyzed using NVivo12 according to the principles of grounded theory. Sixty-one NHB women with personal (n=37, breast; n=6, ovarian) or family history (n=14, breast; n=2, ovarian; n=2 breast/ovarian) of HBOC participated in a qualitative interview. Participants reported on their own awareness of their family history of HBOC prior to their own diagnosis and how this informed their assessment of their pre-diagnostic risk of HBOC. The impact of family culture and cohesion, including perceptions of a familial ‘culture of silence’ around the sharing of personal or family medical history were also identified as potential barriers to awareness of HBOC risk. Thirty participants with a personal history and seven participants with family history received HBOC genetic testing upon recommendation of their provider or following their own request. Those that declined HBOC genetic testing described misperceptions of HBOC inheritance or expressed a belief that such testing would not be personally beneficial. Participants were also asked to describe family members’ interest in cascade testing and their reasons for accepting or declining HBOC genetic testing. Many participants felt that their daughters would be interested in HBOC genetic testing, but that siblings and other extended family members would decline out of belief that the results would have limited personal utility to themselves and/or their offspring or that a potential positive result would result in distress and life-long worry. Family members’ education status and views on healthcare were also thought to be important factors in their decision. This study is the largest qualitative study of its kind in NHB women with a personal or family history of breast and/or ovarian cancer. These findings suggests that there are significant barriers to HBOC genetic testing in the NHB community, including cultural factors influencing risk perception and the uptake of cascade testing. Culturally sensitive community outreach on the disparate impact of breast and ovarian cancer and how genetic testing may improve NHB cancer outcomes may improve uptake of HBOC genetic testing among at-risk NHB families.

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

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. 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. 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. 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. 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.

Hereditary Breast and Ovarian Cancer Screening Syndrome Profile in Women Diagnosed with Breast Cancer from Paraná State Southwest.

This study evaluated the risk of the hereditary breast and ovarian cancer (HBOC) syndrome in patients with breast cancer by using the Family History Screening 7 (FHS-7) tool, a validated low-cost questionnaire with high sensitivity able to screen the HBOC risk in the population. Women diagnosed with breast cancer (n = 101) assisted by the Unified Health System at the 8th Regional Health Municipal Office of the state of Paraná answered the FHS-7, and the results were analyzed using IBM SPSS Statistics for Windows, Version 25.0. software (IBM Corp., Armonk, NY, USA). The risk of HBOC was 19.80% (n = 20). Patients at risk exhibited aggressive tumor characteristics, such as high-grade tumors (30%), presence of angiolymphatic emboli (35%), and premenopausal at diagnosis (50%). Significant associations between the prevalence of high-grade tumors were observed in women younger than 50 years at diagnosis with HBOC (p = 0.003). Our findings suggest a possible family inheritance associated with worse clinical features in women with breast cancer in this population, indicating that HBOC investigation can be initially performed with low-cost instruments such as FHS-7.

Measuring the impact and sustainability of a statewide program for identifying minority and underserved clients at risk for hereditary breast and ovarian cancer (HBOC): An eight-year follow up including transitions during the COVID pandemic.

e18546 Background: The Georgia Breast Cancer Genomics Program was created with 2011-2014 funding from the Centers for Disease Control and Prevention and the Georgia Department of Public Health (GDPH). In collaboration with GDPH and the Georgia Center for Oncology Research and Education (Georgia CORE), the goal of the program has been to reduce disparities among high-risk minority and underserved women. The objective of this study is to report the 8-year surveillance data for women at increased risk for HBOC in statewide public health centers. The effect of the COVID pandemic on the program and sustainability is also reported. Methods: From 11/1/2012-12/31/2020, the program provided education, outreach and collected surveillance data using an online genetics referral screening tool as recommended by USPSTF. Providers in 159 counties and health centers across Georgia were educated in cancer family history collection and appropriate referral to genetics. When an individual was found to be at high risk, she was referred to the Georgia CORE Genetics Advanced Practice Nurse for additional education, genetic testing and follow-up. Results: Online screenings attributable to GDPH totaled 29,087 with 1,656 positive screens. 28 % of clients were less than 25 years of age and 56 % ranged from 25-54. Race: 33 % white, 41 % black, 15 % Hispanic and 11 % other or N/A. 92 % of referrals were uninsured. Genetic testing was started or completed on 430 clients. 36 individuals declined testing after counseling (reconsideration, insurance, unknown reasons) and were provided with contact information. 47 (11%) pathogenic, clinically significant mutations were identified including 37 (79 %) HBOC related mutations and 10 (21 %) Lynch related mutations. Variants of uncertain significance were identified in 90 (21 %) clients, with multiple variants in 40 of those. 27 clients have been served through GDPH for physician consultation and surveillance. 13 were referred to area resources: one diagnosed with cancer, and 7 chose referral to other health care providers. Because of the pandemic, the program transitioned to telecommunications and remote access to testing in 5/2020. From 5/2020-12/2020, 34 clients completed testing (41% minority, all uninsured). 10 (29%) clinically significant mutations were identified and heightened surveillance initiated. Conclusions: The GDPH and Georgia CORE collaborative genomics program has served clients over the past 8 years, adjusting to changing resources while reaching a significant number of minority and underserved women. The program successfully converted to remote services during the COVID pandemic. Lessons learned from this transition have been incorporated into planning for future program sustainability.

Use of a Standardized Tool to Identify Women at Risk for Hereditary Breast and Ovarian Cancer

ObjectiveTo increase rates of identification and genetic counseling referral for women at risk of hereditary breast and ovarian cancer (HBOC). DesignEvidence-based practice improvement initiative. Setting/Local ProblemPrivate suburban obstetric and gynecologic (OB/GYN) practice in Tennessee with no standardized process for HBOC risk assessment or referral to genetic services. ParticipantsProvider-led women's health care teams delivering well-woman care for women ages 18 years and older. Intervention/MeasurementsWe implemented the use of a standardized familial risk assessment tool and clinical decision-making algorithm. Preimplementation and postimplementation risk identification and genetic services referral rates were measured, as was clinicians’ compliance with using the risk assessment tool. The aim of the initiative was to increase identification and referral rates by 25 percentage points. ResultsWomen at risk of HBOC in the postimplementation group were 25.9 times more likely to be identified as being at risk (OR = 25.88, 95% confidence interval [10.78, 62.14]) and 31.5 times more likely to be offered referral to genetic counseling (OR = 31.50, 95% CI [13.37, 74.22]) compared with those in the preimplementation group. Rates of risk identification and referral to genetic counseling for women at risk of HBOC improved by 58.2 and 69.3 percentage points, respectively, surpassing the aims of this initiative and showing statistical significance of p < .001 for both indices. ConclusionThe use of a standardized risk assessment tool and process for HBOC risk identification and genetic referral resulted in a significant increase in the identification and referral of women at risk in this setting. Early identification of women with HBOC is a crucial first step in increasing the use of enhanced screening and interventions that can reduce HBOC-associated cancer morbidity and mortality.

Familial pancreatic cancer: who should be considered for genetic testing?

Determining how many female patients who underwent breast imaging meet the eligibility criteria for genetic testing for familial pancreatic cancer (FPC). A total of 42,904 patients seen at the Newton-Wellesley Hospital between 2007 and 2009 were retrospectively reviewed. The first four categories were based on pancreatic cancer-associated syndromes: (1) hereditary breast and ovarian cancer (HBOC), (2) Lynch syndrome (LS), (3) familial atypical multiple mole melanoma (FAMMM), and (4) family history of FPC (FH-FPC). PancPRO (5) and MelaPRO (6) categories were based on risk scores from Mendelian risk prediction tool. Exactly 4445 of 42,904 patients were found to be in at least one of the six risk categories. About 5.7% of patients were classified as being at high risk for HBOC, 2.3% as being at high risk for LS, 0.1% as being at high risk for FAMMM, 0.1% as being at high risk for FH-FPC, 2.7% as being at high risk based on PancPRO, and 0.2% as being at high risk based on MelaPRO. About 10.4% of the female patients were classified as being at high risk for FPC. This finding emphasizes the importance of applying criteria to the general population, in order to ensure that individuals with high risk are identified early.

Process evaluation of a culturally targeted video for Latinas at risk of hereditary breast and ovarian cancer.

This paper presents a process evaluation of a culturally targeted narrative video about hereditary breast and ovarian cancer (HBOC) for Latina women at risk for HBOC. Spanish-speaking Latina women at risk for HBOC participated in a single arm study (n=40). Participants watched the video developed by the authors and responded to surveys. We used mixed methods to assess theoretical constructs that are hypothesized mediators of narrative interventions (i.e., transportation or engagement, identification with characters, emotions) and implementation outcomes (e.g., acceptability). Descriptive statistics summarized theoretical constructs and implementation outcomes. We conducted Mann-Whitney U tests to assess the differences in theoretical and implementation outcomes between participants who were affected versus. unaffected and participants with different levels of education and health literacy. We used the consensual qualitative research framework to analyze qualitative data. Participants' mean age was 47.1years (SD=9.48). Most participants were high school graduates or less (62.5%). Acceptability of the video was extremely high (Md=10.0, IQR=0.2, scale 1-10). Most (82.5%) suggested video dissemination be through social media. Participants were highly engaged (Md=5.7, IQR=1.5, scale 1-7), strongly identified with the main character (Md=8.7, IQR=2.6, scale 1-10), and reported experiencing mostly positive emotions (Md=9.5, IQR=2.8, scale 1-10). Participants with low health literacy and affected participants reported a significantly higher identification with the main character (p<.05). Qualitative data reinforced the quantitative findings. Women reported gaining knowledge, correcting misconceptions, and feeling empowered. Our culturally targeted video is highly acceptable and targets mechanisms of behavior change for narrative interventions. The video is easily disseminable and can be used as an education tool for patients including affected and unaffected women and patients with different education and health literacy levels. Future studies should test the impact of the video in enhancing genetic counseling and testing uptake.

"It wasn't just for me": Motivations and implications of genetic testing for women at a low risk of hereditary breast and ovarian cancer syndrome.

Genetic testing for hereditary breast and ovarian cancer (HBOC) due to pathogenic variants in BRCA1 or BRCA2 is why most women present to familial cancer centers. Despite being assessed as low risk for HBOC, many women proceed with genetic testing. This study explored the genetic testing experiences of unaffected women at low risk of HBOC to clarify what motivates these women to have testing, and what are the implications of the results. A qualitative approach was taken. Participants included women who had genetic testing for HBOC from 2016-2018 at the Parkville Familial Cancer Centre in Melbourne, Australia. In-depth, semi-structured interviews were conducted, and thematic analysis was undertaken on transcripts; transcripts were coded, codes were organized into a hierarchical system of categories/subcategories, and key themes were identified. Analysis of 19 transcripts identified five themes: family underpinned all motivators for HBOC genetic testing; health professionals were influential throughout the process; participants were planning for a positive result; results influenced screening-anxiety and frequency; and negative results gave participants relief in many different ways. The three participants with positive results reported feeling shocked at the results and empowered giving this information to family members. Women at low HBOC risk may be motivated to seek genetic testing, and access to this is increasingly offered through non-genetic health professionals. Professionals can support clients through genetic testing by recognizing familial experiences, providing accurate information, addressing risk perceptions, and understanding cancer anxiety felt by many women.

Population genetic screening for hereditary breast and ovarian cancer in at-risk patients: A novel testing and prevention model for community hospitals reveals high mutation rates rurally.

1575 Background: Genetic testing for at risk non-cancer patients continues to increase (Guo F, et al Cancer 2020). We identified a high risk of familial breast and ovarian cancer in rural eastern North Carolina, and created a systematic approach for genetic screening, counseling and testing. Methods: A family history questionnaire was designed to assess for the risk for hereditary breast and ovarian cancer (HBOC) using NCCN guidelines, and used at key intake points within the unaffected population to determine eligibility for genetic testing. First it was offered at the time of all mammograms. Second, we offered it in the primary gynecology care setting to capture younger patients not participating in screening mammography. Patients meeting HBOC criteria were sent a letter and two phone calls to schedule genetic counseling. Analysis via descriptive statistics. Results: 3000 rural women screened using our systematic approach to genetic risk assessment. 22.4% (673/3000) of female patients met NCCN criteria for HBOC panel testing. All offered consultation and counseling. With a backlog to see patients due to higher than expected accrual, 217 patients have completed pre-test genetic counseling, 201 completed local 19-gene panel test, and 201 had post-test counseling. Germline mutations (=&gt;1) that predict for genetic susceptibility to cancer(s) occur in 7.8% of our screened and tested population. Currently 1 in 400 patients screened in our unaffected population carry a BRCA mutation, and 1 in 200 carry some pathogenic mutation that increases risk for HBOC. Conclusions: This rural model of screening and prevention of at risk patients for HBOC is successful at detecting pathogenic mutations in unaffected patients before they are diagnosed with cancer. Interestingly, the rate of positivity in the unaffected population (meeting criteria) is as high as the known breast cancer population rate of germline mutations (5-10%), validating the use of testing guidelines with our model. Discovering this susceptibility before a cancer diagnosis resulted in appropriate high risk management with prevention and risk reduction strategies. We plan to expand this model to the male screening population in 2021, and streamline genetic assessment and testing for the larger population at risk by engaging more rural primary care clinics over time to increase testing compliance. We also plan to consider broader gene panels as newer mutations become linked to HBOC. Clinical trial information: UMCIRB 19-001052.