Genetic cancer risk knowledge among Mexican pathogenic variant carriers.

Women with pathogenic variants (PVs) in breast cancer (BC) and ovarian cancer (OC) associated genes are candidates for cancer risk-reducing strategies. Limited information is available regarding risk-reducing surgeries (RRS) among Hispanics. The aim of this study was to describe the uptake of RRS in an international real-world experience of Hispanic women referred for genetic cancer risk assessment (GCRA) and to identify factors affecting uptake. Between July 1997 and December 2019, Hispanic women, living in the United States or in Latin America, enrolled in the Clinical Cancer Genomics Community Research Network registry were prospectively included. Demographic characteristics and data regarding RRS were obtained from chart reviews and patient-reported follow-up questionnaires. Median follow-up was 41 months. Among 1,736 Hispanic women referred for GCRA, 27.2% women underwent risk-reducing mastectomy (RRM), 25.5% risk-reducing salpingo-oophorectomy (RRSO) and, 10.7% both surgeries. Among BRCA carriers, rates of RRM and RRSO were 47.6% and 56.7%, respectively. In the multivariate analyses, being a carrier of a BC susceptibility gene (odds ratio [OR], 3.44), personal history of BC (OR, 6.22), living in the US (OR, 3.90), age ≤50 years (OR, 1.68) and, family history of BC (OR, 1.56) were associated with a higher likelihood of undergoing RRM. Carrying an OC susceptibility gene (OR, 6.72) was associated with a higher likelihood of undergoing RRSO. The rate of RRS among Hispanic women is suboptimal. PV carriers, women with personal history of cancer, and those with a family history of cancer were more likely to have RRS, with less uptake outside the US. Understanding personal and systemic factors influencing uptake may enable interventions to increase risk appropriate uptake of RRS.

IA23: Steps to address the profound disparity in access to genetic cancer risk assessment in Mexico: Documenting hereditary breast and ovarian cancer and the beginning of a prevention program

Introduction: GCRA, which includes genetic counseling and testing, identifies individuals at hereditary cancer risk. Despite recognition of GCRA as standard-of- care, Latinas remain underrepresented in clinics and little is known about their experience. Our study examines the effect of an adapted motivational interviewing (AMI) telephone intervention on GCRA uptake. Perceived personal control (PPC) assesses cognitive, behavioral and decisional locus of control relative to the possibility of having a hereditary condition. Purpose: 1) Evaluate the effect of an AMI intervention on GCRA uptake 2) Explore baseline PPC and how it is affected by GCRA and AMI Procedures: English or Spanish speaking adult Latinas, who met NCCN criteria for BRCA testing were eligible and approached when scheduling their GCRA at two safety-net hospitals and one cancer center. Participants were randomized to an AMI intervention, time-and-attention control health habits (HH), or usual care (UC). The 9-item validated PPC instrument (scored 0-2, no PPC to full PPC) was administered in participants’ preferred language at baseline, pre- and post-GCRA. Results: Of the 478 Latinas who consented, 152 (32%) were randomized to both the AMI and UC arms, and the remaining 174 (36%) assigned to the HH arm. Spanish was the primary language for 76% (n=362). The majority had a history of cancer (79%, n=375) and most (64%, n=241) were undergoing treatment at the time of GCRA. There was no difference in the demographics of each arm (p>0.22). There was no difference in GCRA uptake by arm with 79% (n=379) keeping their appointment. Baseline PPC: PPC scores were not different between the arms for total PPC (AMI = 1.36, HH = 1.36, UC = 1.37; p = 0.67). Domain scores were: cognitive = 1.22, behavioral = 1.32 and decisional = 1.54. Post-GRCA PPC: PPC increased 12% for the cohort and in the arms, with no difference in the magnitude of increase between arms (p>0.68). The greatest increase was observed in cognitive PPC (>17%) across the cohort. In the AMI arm, total PPC increased 11% for those with cancer (p=0.043) and English speakers had an increase of 20% compared to 11% for Spanish speakers. Behavioral PPC increased by 14% in both the AMI and UC arms (p=0.004). Decisional PPC increased 8.9% in the AMI arm (p=0.026). Conclusions: PPC scores increased post-GCRA, with no between-arm differences, suggesting that the shared exposure to GCRA may increase PPC for Latinas. AMI did not impact GCRA uptake, though we did observe an increase in PPC scores in this arm for English speakers and those with cancer. Therefore, the addition of AMI to GCRA may be particularly effective in increasing PPC for some patients. The most significant increases in post-GCRA PPC were observed in cognitive PPC, likely reflecting the educational focus of GCRA but also supports a need for focus on approaches to enhance decisional and behavioral control. This is further supported by our finding that an increase in decisional control was only seen in the AMI arm. This merits further exploration and study. Citation Format: Charité Ricker, Bita Nehoray, Guadalupe M. Carvajal, Kathleen R. Blazer, Sharon Sand, Kimlin Ashing, April Vang, Kai Wang, Nancy Feldman, Jeffrey N. Weitzel. Genetic cancer risk assessment (GCRA) increases perceived personal control in Latinas at risk for hereditary breast and ovarian cancer [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-049.

Germline genetic testing for cancer risk offers opportunities for decision-making about screening and clinical risk management for individuals and their family members. Despite increasing availability of cancer genetic testing, Black individuals are still much less likely to receive or engage with testing compared to non-Hispanic white individuals. We sought to identify individual level factors influencing knowledge about and attitudes toward cancer genetic testing among Black women with and without breast cancer. Participants included 925 women from the Black Women’s Health Study who had previously provided a biospecimen for research and were invited to have their cancer genetic research findings confirmed via a CLIA-certified laboratory and learn their results as part of a randomized controlled trial. Prior to confirmation testing, all women completed a baseline questionnaire about personal and family history of cancer; prior genetic testing for hereditary cancer; and knowledge, attitudes, and confidence in one’s ability to use genetic information (genetics self-efficacy). We used linear regression to evaluate individual-level factors influencing cancer genetics knowledge, attitudes, and self-efficacy. Overall, mean knowledge score was 12.3 out of 16 (SD, 2.5); there were no differences in knowledge score between women who had a personal history of breast cancer and those who did not. While the majority of women answered most questions correctly, 20-30% of women were unable to correctly answer questions about validity of test results, clinical implications of a variant of uncertain significance, and legal protections against health insurance discrimination. Younger age, higher educational attainment, being married, and having had prior genetic testing were statistically significant predictors of higher total knowledge score. There were no differences in mean knowledge scores by first degree family history of breast cancer or personal history of breast or other cancer. Predictors of favorable attitudes and genetics self-efficacy included younger age, higher educational attainment, and being married. Women with a personal history of breast cancer had somewhat more favorable attitudes toward genetic testing compared to those with no prior history of breast cancer. In multivariable adjusted models, higher total knowledge was associated with more favorable attitudes and higher self-efficacy. In this cohort of highly educated Black women, overall cancer genetics knowledge was relatively high; however, evaluation of individual knowledge questions revealed opportunities for improvement in specific areas. Older women, those with lower educational attainment, and women who are not married or living as married may benefit from more targeted education about genetic cancer testing. Further, despite the role genetic testing currently plays in guiding cancer treatment, Black women who had breast cancer did not have higher knowledge scores than those without breast cancer and therefore may also benefit from targeted education. Citation Format: Kimberly A. Bertrand, Michelle Trevino-Talbot, Maggie Rudderman, Maureen Flynn, Howard J. Cabral, Julie R. Palmer, Catharine Wang. Knowledge, attitudes, and self-efficacy toward cancer genetic testing among Black women with and without breast cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B101.

Selection of family members for communication of cancer risk and barriers to this communication before and after genetic cancer risk assessment

The management of cancer risk for BRCA pathogenic variants (PV) carriers varies depending on countries, with different strategies. However, some strategies lack of cost-effectiveness evidence. This study fills this gap assessing the cost-effectiveness of a combined ovarian cancer (OC) surveillance and prevention strategy in BRCA1/2 PV carriers. The developed Markov decision model simulated the progression of breast cancer and OC in BRCA1/2 PV carriers separately. The model estimated benefits and costs associated with three OC surveillance strategies: Surveillance-Surgery (SS), annual surveillance until salpingo-oophorectomy (SO) and radical mastectomy (RM) at appropriate age; Only-Surgery (OS), without surveillance, and No preventive Intervention (NI). Extensive literature review informed the model. The analysis adopted the Italian NHS perspective and a lifetime horizon, with direct healthcare costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio as outcome measures. Base-case, deterministic and probabilistic sensitivity analyses were performed. In BRCA1 PV carriers, SS yielded lifetime cost savings of €8 382 and €2 008 compared to NI and OS, respectively, while also gaining 2.65 and 0.45 QALYs per patient. Similar trends were observed for BRCA2 PV carriers. Sensitivity analyses confirmed SS as the dominant strategy across all scenarios, with a > 80% probability of being most cost-effective at a willingness-to-pay threshold of €20 000 per QALY gained. Combined OC surveillance and prevention strategy for BRCA1/2 PV carriers at appropriate age represents a highly cost-effective approach compared to surgical prophylaxis alone or no intervention. Periodical counselling in a multidisciplinary team affects high surgical acceptance rates, that are crucial for maximizing the effectiveness of such programs. Some countries advise transvaginal ultrasound and CA125 tests every 6 months from age 30, along with risk-reducing surgery. Annual surveillance until salpingo-oophorectomy and mastectomy saves costs over surgery alone or no preventive measures. High surgical acceptance rates are crucial for maximizing the effectiveness of this programs.

e22552 Background: Genetic cancer risk assessment (GCRA) has become an integral component of the management of patients with colorectal cancer (CRC). Understanding clinical criteria and interpreting screening tests to identify patients who should be prioritized for genetic testing is especially critical in resource-constrained settings such as Mexico, where access to genetic testing is limited. Methods: We designed a self-applicable survey consisting of 18 items, divided into three sections: 7 on knowledge, 5 on clinical approaches, and 6 on access to genetic testing. The aim was to assess the practice patterns of Mexican physicians in contact with patients at risk for hereditary CRC. Initially, the survey was piloted among oncology fellows to refine and improve its relevance and applicability. Following adjustments, it was disseminated using a QR code at the annual meeting of the Mexican Society of Oncology (SMeO) in September 2023. Descriptive statistics were performed using frequency and proportions for categorical variables and median and range for quantitative variables. Results: A total of 78 physicians completed the survey, with a median age of 37 years (range, 27-70). Among them, 47.2% were female, 82% were medical oncologists, with a median practice duration of 6 years (range, 1- 40). 52.6% practice in cancer community centers, 83.4% were employed in public primary care settings, and 60% were affiliated to academic centers. Referral criteria for GCRA was identified correctly in 66.7% who recognized age at CRC diagnosis < 50 years, 57.7% synchronous or metachronous CRC, 50% deficient mismatch repair CRC, and 37.2% PREMM5 score of ≥2.5%. Lynch syndrome, Familial Adenomatous Polyposis (FAP), and Cowden syndrome were identified as syndromes with an increased CRC risk by 76.9%, 71.8% and 56.7% of respondents, respectively. Decision-making based on likely pathogenic and pathogenic variants was indicated by 26.9% and 69.2%, while 12.8% reported making decisions based on variants of uncertain significance (VUS). Regarding clinical approach, 74.4% inquired about a family history of cancer at the initial consultation, and 66.7% referred patients for genetic counseling. The primary obstacles to accessing GCRA were the cost of genetic testing (43.6%) and the absence of medical genetics services at their centers (39.7%). Only 23% reported the availability of cascade testing within their practice. Conclusions: The identification of patients at risk of hereditary CRC was suboptimal among Mexican physicians. A high proportion of respondents were not fully qualified to interpret correctly genetic testing results. These indicate a need for awareness and educational programs to improve providers’ knowledge on predisposition cancer syndromes.

Background: Long-term follow-up surveys of Spanish-speaking Latina patients at increased risk for hereditary breast cancer who completed genetic cancer risk assessment (GCRA) in our underserved clinics revealed a need for ongoing education and support. Consequently, we invited patients back for a half-day educational conference, employing mixed methods research to better understand their medical and social/cultural issues and needs.Aims: The conference aims were to: 1) share medical advances in GCRA and cancer screening and prevention recommendations and resources and 2) explore GCRA-related experiences and needs, and access to risk-appropriate care.Methods: Invitees were Latina patients with personal and/or family history of breast cancer who completed GCRA between 2001-2009 and their family members. The conference, conducted entirely in Spanish, was held at the regional county medical facility where our underserved clinic is conducted. Educational information was delivered by podium-presentations, expert and patient panel discussions and interactive sessions and community resource booth exhibits. Mixed methods research (surveys and Audio Response System [ARS] mediated interaction and discussion) was used to explore GRCA experiences and access to care.Results: The 71 primarily Spanish speaking (96%) participants ranged in age from 18 to 71 years (mean age, 44), were female (93%), had children (78%), and had at least completed high school (71%). Of the 41 patient-participant, 78% were accompanied by at least one family member and/or friend. Thirty (73%) had a personal history of breast cancer; 4 also had ovarian cancer. Of the 35 tested, 20 (57%) were BRCA positive. Nearly all participants (96%) completed the voluntary survey and post-conference evaluation. On average, 87% responded to eight ARS questions related to the GCRA process and access to care. The majority of patient-participant (71%) understood why they were referred for GCRA, 15% did not, and 13% were uncertain. Eighty percent understood their cancer risk; however 20% expressed a need for more risk information. Although 83% understood cancer screening recommendations, 17% were unsure and requested more information. Interestingly, only 5% reported lack of access to care. More than 75% found the GCRA process stressful and desired more support and preparedness for sharing information with relatives. All responders (96%) reported that the conference met their expectations, valued the resources provided, and suggested allocating more time for questions in a future conference.Conclusion: The interactive conference format was highly rated and effective in providing Latina breast cancer patients and family members with ongoing education and support following GCRA, and provided important information to guide improvement in the risk assessment process. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3073.

1554 Background: Medically underserved women bear a disproportionate burden of breast cancer (BC) mortality. Early detection is vital for reducing BC deaths. Cancer genetic risk assessment (CGRA) provides an opportunity to identify women at highest risk so that risk-adapted screening can be implemented. The effect of CGRA on mammography adherence among underserved women is unknown. Methods: We conducted a study to test the feasibility of performing cancer genetic risk assessment (CGRA) as part of standard primary healthcare at two Federally Qualified Health Centers in Chicago, IL. Racial/ethnically diverse women age 25-69 without a personal history of BC underwent CGRA at the time of an annual well-visit and received the result from their PCP. Medical record review provided data on mammography adherence. Demographic data and measures of perceived BC risk, BC cultural beliefs, fatalism, and BC worry were collected with an enrollment survey. McNemar’s test compared the rate of adherence to screening mammography before and after implementation of CGRA, defined as completing a screening mammogram within 18 months prior to or following CGRA, resp., among women eligible for screening (age > 40 at study enrollment). Logistic regression models tested for associations between mammography adherence and demographic characteristics/health beliefs. Results: Data was available for 90 participants with increased BC risk (IR) who were eligible for screening and 98 eligible, average risk (AR) participants (in total, 61% black and 37% Latina). Overall, adherence improved from 38% at baseline to 49% following CGRA (p = 0.03). Adherence increased from 35% to 51% among IR participants (p = 0.04), and from 40% to 47% among AR participants (p = 0.39). Data on predictors of adherence will be presented. Conclusions: Implementing CGRA as a standard component of primary healthcare improved adherence to screening mammography among racial/ethnically diverse underserved women. The effect was seen primarily in those with increased risk. This intervention could be used to improve uptake of mammography in the subgroup of underserved women who benefit the most from screening.

Some communities and populations lack access to genetic cancer risk assessment (GCRA) and testing. This is particularly evident in safety-net institutions, which serve a large segment of low-income, uninsured individuals. We describe the experience of a safety-net clinic with limited resources in providing GCRA and BRCA1/2 testing. We compared the proportion and characteristics of high-risk women who were offered and underwent GCRA and genetic testing. We also provide a description of the mutation profile for affected women. All 125 patients who were offered GCRA accepted to undergo GCRA. Of these, 72% had a breast cancer diagnosis, 70% were Hispanic, 52.8% were non-English speakers, and 66% did not have health insurance. Eighty four (67%) were offered genetic testing and 81 (96%) agreed. Hispanic women, those with no medical insurance, and those with a family history of breast cancer were significantly more likely to undergo testing (p > 0.01). Twelve of 81 (15%) patients were found to have deleterious mutations, seven BRCA1, and five BRCA2. Our experience shows that it is possible to offer GCRA and genetic testing even in the setting of limited resources for these services. This is important given that a large majority of the low-income women in our study agreed to undergo counseling and testing. Our experience could serve as a model for similar low-resource safety-net health settings.

Over 90% of people with hereditary cancer syndromes in the United States remain unidentified. The Genetic Cancer Risk Detector (GARDE) is an open-source, electronic health record (EHR)-integrated, digital health platform that can facilitate genetic cancer risk assessment and genetic testing. This study evaluates its budget impact on health care institutions. A budget impact analysis was performed from the perspective of a US health care provider system over a 3-year horizon. Data from the BRIDGE randomized controlled trial data from the University of Utah Health (UHealth) were used, where eligible primary care patients were screened for genetic cancer risk via GARDE. Costs of GARDE were categorized across planning, implementation, and operational phases. Revenue projections were based on Centers for Medicare & Medicaid Services reimbursement rates. Scenario analyses varied uptake of interventions, surveillance intervals, reimbursement rates, and implementation scale. Of 1,444 patients identified by GARDE at UHealth and enrolled in the BRIDGE trial, 205 completed genetic testing, with 15 found to carry pathogenic variants. The total 3-year implementation cost was $29,217 US dollars (USD). Revenue from guideline-recommended procedures totaled $86,563 USD, yielding a net positive budget impact of $57,347 USD. Most revenue (76.4%) was generated by surgical risk-reduction procedures. Scenario analyses revealed high sensitivity to cancer risk-reducing surgery uptake and implementation scale. Modeling 100% uptake of risk-reducing surgeries increased revenue to $128,102 USD, while 20-fold scaling of the implementation population increased revenue to $1.7 million USD. Commercial insurance reimbursement assumptions further amplified revenue. GARDE enables scalable hereditary cancer risk assessment within a health care provider system. Even with modest uptake, it yields a positive financial return, and significantly greater revenue is achievable with broader implementation. These findings support adoption of EHR-integrated tools to enhance clinical outcomes in precision cancer prevention and risk management, in an economically viable manner.

BackgroundClinical management of women carrying a germline pathogenic variant (PV) in the BRCA1/2 genes demands for accurate age-dependent estimators of breast cancer (BC) risks, which were found to be affected by a variety of intrinsic and extrinsic factors. Here we assess the contribution of polygenic risk scores (PRSs) to the occurrence of extreme phenotypes with respect to age at onset, namely, primary BC diagnosis before the age of 35 years (early diagnosis, ED) and cancer-free survival until the age of 60 years (late/no diagnosis, LD) in female BRCA1/2 PV carriers.MethodsOverall, estrogen receptor (ER)-positive, and ER-negative BC PRSs as developed by Kuchenbaecker et al. for BC risk discrimination in female BRCA1/2 PV carriers were employed for PRS computation in a curated sample of 295 women of European descent carrying PVs in the BRCA1 (n=183) or the BRCA2 gene (n=112), and did either fulfill the ED criteria (n=162, mean age at diagnosis: 28.3 years, range: 20 to 34 years) or the LD criteria (n=133). Binomial logistic regression was applied to assess the association of standardized PRSs with either ED or LD under adjustment for patient recruitment criteria for germline testing and localization of BRCA1/2 PVs in the corresponding BC or ovarian cancer (OC) cluster regions.ResultsFor BRCA1 PV carriers, the standardized overall BC PRS displayed the strongest association with ED (odds ratio (OR) = 1.62; 95% confidence interval (CI): 1.16–2.31, p<0.01). Additionally, statistically significant associations of selection for the patient recruitment criteria for germline testing and localization of pathogenic PVs outside the BRCA1 OC cluster region with ED were observed. For BRCA2 PV carriers, the standardized PRS for ER-negative BC displayed the strongest association (OR = 2.27, 95% CI: 1.45–3.78, p<0.001).ConclusionsPRSs contribute to the development of extreme phenotypes of female BRCA1/2 PV carriers with respect to age at primary BC diagnosis. Construction of optimized PRS SNP sets for BC risk stratification in BRCA1/2 PV carriers should be the task of future studies with larger, well-defined study samples. Furthermore, our results provide further evidence, that localization of PVs in BC/OC cluster regions might be considered in BC risk calculations for unaffected BRCA1/2 PV carriers.

Background: The prevalence of germline pathogenic variants in Mexican women with breast cancer who met the reference criteria for genetic cancer risk assessment (GCRA) has been previously reported as close to 20%. However, information regarding the spectrum of gPVs in genes other than BRCA in this population is limited. Methods: This prospective study included Mexican women who were diagnosed with BC and met international criteria for GCRA. Participants were enrolled in the Clinical Cancer Genomics Community Research Network (CCGCRN) registry and at two referral breast cancer centers in Mexico, the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City and at the Hospital Zambrano Hellion TecSalud, Monterrey. Participants underwent multigene panel testing (MGPT) for 37 cancer susceptibility genes. For this analysis, only the results of pathogenic and likely pathogenic variants in the index cases were reported. The demographic and molecular characteristics of the variants are described here. Results: From August 2017 to September 2021, 1020 Mexican women with BC underwent MGPT, with a median age at diagnosis of 41 y (range 20-86), of whom 206 (20.2%) were carriers. 208 gPVs were identified with BRCA1/2 representing 70% (145/208) of the gPVs (BRCA1 n=89, BRCA2 n=56). 63 (30%) of gPVs were identified in genes other than BRCA (CHEK2 n=21, PALB2 n=13, TP53 n=7, RAD51C n=5, ATM n=4, NF1 n=3, PTEN n=2, MUTYH homozygous n=2, RAD50 n=1, BRIP1 n=1, CDH1 n=1, NBN n=1, MSH2 n=1 and MSH6 n=1). The recurrent variants previously proposed as founders in the Hispanic population were frequent among those identified in their respective genes: CHEK2 c.707T&amp;gt;C 81% (17/21), PALB2 c.2167_2168delAT 46% (6/13) and BRCA1 del(exons 9-12) 18% (16/89). As a group, the 4 most frequent genes where gPVs were identified (BRCA1, BRCA2, CHEK2 and PALB2) represented 86% (179/208) of the positive results. Conclusion: Among the variants identified in this population of Mexican women with BC, the proportion of gPVs in genes other than BRCA was significant (about 1 out of 3 pts), which justifies the use of MGPT in the assessment of our population. However, a tailored panel (sequencing of BRCA1/BRCA2/CHEK2/PALB2 and MLPA for BRCA1) could be proposed in areas of Mexico with limited medical resources, including the analysis of other genes in selected patients according to clinical suspicion and family history of cancer. Citation Format: Yanin Chavarri-Guerra, Cynthia Villareal Garza, Jose Luis Rodriguez-Olivares, Dione Aguilar-y Mendez, Gregorio Quintero-Beulo, Francisco Gutierrez-Delgado, Josef Herzog, Stephen Gruber. Prevalence of non-BRCA germline pathogenic variants in Mexican women with breast cancer referred for genetic cancer risk assessment [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-02-05.

Genetic Cancer Risk Assessment

Effect on perceived control and psychological distress of genetic knowledge in women with breast cancer receiving a BRCA1/2 test result