Pathogenic mutations in ethnic Lebanese Arab patients with high risk for hereditary breast cancer

Background: Breast cancer accounts for 35-40% of cancer in women in Lebanese and Arab countries with 50% of patients (pts) diagnosed before age 50. Prevalence of pathogenic BRCA variants in high-risk pts is 5.6-20% (Abulkhair and El Saghir 2021). 7 BRCA1 and 7 BRCA2 pathogenic variants were found in 5.6% of 250 pts with high hereditary risk breast cancer using amplicon sequencing and MLPA (El Saghir 2015;Poulet 2016). We report results of Next Generation Sequencing (NGS) on selected cases based on Manchester Score. First report in ethnic Lebanese Arab pts. Method(s): Pts prospectively enrolled in 2009-2012. IRB approval secured. Pts signed informed consent. Data collected from medical records. Amplicon and MLPA was done on 250 patients. NGS was done on 100 cases with Manchester Score 14-56. DNAs of the 14 pts previously found to have a pathogenic variant (Manchester Score 10-59) were not re-sequenced. NGS on remaining 150 pts was not done due to Covid-19 pandemic and lack of additional funding. Result(s): NGS showed 7 pathogenic variants, 4 in PALB2 and 3 in ATM. No new BRCA variants were found. Two BRCA2 mutations noted by Amplicon/MLPA reported as VUS in 2015 are reclassified as pathogenic. Total BRCA2 pathogenic variants becomes 9. Total pathogenic variants 23. Risk of having hereditary breast cancer in pts with MS 10-59 is 20% (23/ 114), and at least 9.2% in the entire cohort (23/250). Age <=40 with family history (FH) carries 18.9% risk of harboring a pathogenic mutation while no FH, 1.4% (Table 1). All BRCA1 pts had triple negative and 7/9 BRCA2 pts had hormone receptor positive breast cancer. 4 unrelated pts shared the same c.1056_1057delGA PALB2 pathogenic variant thus we suggest this is a founder mutation in Lebanese Ethnic Arab population. Conclusion(s): Mutation rates in high hereditary risk pts with Manchester Score range 10-59 is 20%. Age <=40 with positive FH can be used to select pts for testing when resources are limited. Our data suggests that c.1056_1057delGA is a PALB2 founder mutation. No conflict of interest.Copyright © 2022 Elsevier Ltd. All rights reserved

Screening for genetic risk at the time of mammography

Introduction: Approximately, 10-15% of breast cancers may be hereditary. Early identification of elevated genetic risk may decrease morbidly and mortality associated with breast cancer for this population by enabling timely implantation of optimized screening techniques. Reaching out to women with breast cancer risk assessment at the time of mammography may provide an opportunity to connect risk perception with risk reduction action. We hypothesized that women receiving a high-risk assessment at the time of mammography would facilitate entry to genetic counseling. Methods: In September 2019, Jefferson Health New Jersey (JHNJ) started utilizing a tool to screen individuals for an increased risk for hereditary breast cancer syndromes (family history screening 7;FHS-7) to all women presenting for mammography at its three breast imaging centers. The FHS-7 tool was embedded into the electronic medical record system and would generate a score based on 7 questions related to a patient's family history of breast, ovarian and bowel cancer. Women who were identified at elevated risk (FHS-7 scores ≥1) were asked by the mammography technician prior to performing the screening mammogram for their permission to be contacted by a high-risk counselor for a formal high-risk assessment and potential genetic counseling/testing. In March 2020, nearly all cancer screening services shut down with the COVID-19 pandemic. Services re-opened in June 2020. We report on our experience in three-time frames: September 2019-February 2020;March 2020-May 2020, and June 2020-present. Results: From September 2019-February 2020: 3, 169 mammograms and FHS-7 screenings were performed. 44 had scores ≥1 (1.4%). 4 (9%) agreed to be contacted for an appointment with a high-risk counselor. Of these, 2 had previously met with genetics. No additional appointments were scheduled. From March 2020-May 2020, 576 mammograms and FHS-7 screenings were performed. 9 had scores ≥1 (1.6%). None agreed to be contacted for an appointment with a high-risk counselor. Two appointments had previously been completed. From June 2020-June 2021, 9, 131 mammogramsand FHS-7 screenings were performed. 240 had scores ≥1 (2.6%). 22 (9%) agreed to be contacted for an appointment with genetics. 11 appointments had previously been completed. 8 (73%) were completed as a consequence of this direct outreach. Conclusion: Although our work was interrupted by the COVID-19 pandemic, screening for hereditary risk at the time of mammography may be an effective way of facilitating referrals for genetic counseling/testing for high-risk patients. Consent to be contacted for a formal high-risk assessment was consistent at 9% pre-mammography closure and post-mammography re-opening. Consent to be contacted for genetics is likely to be associated with breast cancer risk perception. Future Directions: We are planning an educational intervention regarding the FSH-7 risk assessment tool and a positive score's association with the risk of hereditary breast cancer syndromes, as well as the benefits of optimized screening techniques depending on a patient's life-time risk of developing breast cancer. We anticipate that this will likely result in greater acceptance of a formal high-risk assessment for this at-risk population.

'Tu historia cuenta' online version: Promotores' experience and perspectives on the virtual adaption of a hereditary breast cancer education and risk identification program

Background: Breast cancer is the most common cancer in women in the U.S. and the leading cause of cancer related death among U.S. Latinas. Despite having lower breast cancer incidence, U.S. Latinas are more likely to be diagnosed with advanced stage disease compared to non-Hispanic White (NHW) women. This can be attributed to lower rates of screening and longer time to follow up after an abnormal mammogram in the former group. We developed a comprehensive promotores-led education and risk stratification program for Spanish-speaking Latinas to increase mammography screening, genetic testing, and the understanding of the impact of family history on cancer risk. Due to COVID-19 we adapted the program to a virtual platform. This study aimed to record and share the experience from the promotores' perspective as they educated the Latino(x) community through virtual sessions. Methods: We used a stakeholder continuous engagement approach and the construct of relational culture to build the program materials. The promotores were part of two organizations in California: Vision y Compromiso (Sacramento region, and San Francisco) and Promoters for Better Health (Los Angeles). Their experience was captured using semi-structured interviews guided by a set of questions and a request for additional thoughts. Demographic information was captured using a questionnaire. The promotores' voices were incorporated into this program through multiple interactions including the revision of the interviews. Results: All promotores (N=14) in the program were fluent in Spanish and self-identified as Hispanics/Latinos(x). Ages ranged between 34 and 62, most being first generation immigrants. Educational achievement varied from high school to college degree. Through the interviews and informal interaction, promotores shared that virtual platforms helped alleviate numerous obstacles for attendance like transportation, scheduling conflicts, and childcare costs. However, the online approach removed the personal connection that promotores usually have with participants. The most important challenge described was the lack of privacy and a safe space for participants to share, since many took the class in the middle of their homes near family members. The promotores agreed delivering the program gave them a greater sense of self-worth and confidence. They never thought that they could learn, and teach, community members about genetics and cancer risk. Conclusions: Despite the challenges brought about by COVID-19, the experience of transforming the 'tu historia cuenta' program to a virtual platform provided unique opportunities for bi-directional collaboration between the academic and community partners and with the participants. Overall, we learned that the virtual program had both positive and negative aspects regarding community engagement. It also consistently empowered promotores as well as allowed them to continue their paid work during lock-down, which was equally appreciated during challenging economic times.