Abstract P6-02-02: Challenges and Dilemmas Following a Traceback Approach for Genetic Counseling and Genetic Testing for Pathogenic Germline Mutations among High-Risk Patients Previously Diagnosed with Breast Cancer
Authors: Tamimi Faris , sharaf Baha’ , Salama Osama , Edaily Sarah , Khater Suhaib , AlKyam Mais , Abujamous Lama , Azzam Khansa , Abu-Fares Hala , Abaza Haneen , Abdel-Razeq Hikmat 
Published: March 2023

Background: Accounting for almost 20% of all cancer cases, breast cancer continues to be the most common cancer and the leading cause of cancer-related deaths among females. In our region, almost 50% of breast cancer patients are diagnosed at age 50 or younger. Around 5-15% of breast cancers are hereditary and mostly related to BRCA1 or BRCA2 gene mutations. Risk-reducing interventions, like bilateral mastectomies and oophorectomies, are highly recommended for carriers of pathogenic variants. More recently, data had shown that specific breast cancer treatment may be informed by BRCA1 or BRCA2 mutation status. Until very recently, genetic testing and genetic counseling services were prohibitively expensive and were not available or routinely offered. Given the recently identified high prevalence of pathogenic variants among our patients, and the wider availability and the lower cost of genetic testing, an opportunity exists to look back and offer such patients the chance to do genetic testing. Patients with positive tests can then be counseled, along with their close family members, for appropriate risk-reducing programs. Methods: Using our hospital-based cancer registry, we identified patients with breast cancer who fulfilled at least one of 3 approved indications for genetic testing but never had it. Eligible patients were those diagnosed at age 45 or younger, patients with triple-negative (TN) disease diagnosed at age 65 years or younger, and those with close blood relatives with breast or ovarian cancers. Patients were initially contacted over the phone and then seen by one of the investigators in our genetic counseling clinics. Testing was performed using next-generation sequencing (NGS)-based multi-gene panel (MGP) on a peripheral blood sample at a referral lab. Results: A total of 377 eligible patients were identified. The median age (range) was 48 (31-75) years. Genetic testing was performed on 198 (52.5%) and results were reported on 192. Age ≤45 years (n= 157, 79.3%) and TN-disease (n= 59, 29.8%) were the most common indications for testing. In total, 20 (10.4%) patients were found to have pathogenic/likely pathogenic variants; mostly in BRCA2 (n=9) and BRCA1 (n=7). An additional 4 patients had TP53, PALB2, and ATM. Variants of uncertain significance (VUS) were identified in 53 (27.6%) patients. Following the visit to the genetic counseling clinic, an additional 41 (22.9%) patients agreed to test. The remaining 136 (36.1%) failed to be tested because of lack of updated contact information (n=54, 39.7%), living outside the country (n=19, 14.0%) or lack of insurance coverage (n=36, 26.5%). Fear of social stigma, lack of interest, or emotional stress were the reason for refusal among 24 (17.6%) patients. Conclusions: The Traceback approach may provide an opportunity to diagnose pathogenic/likely pathogenic variants among previously diagnosed patients with breast cancer. The high percentage of patients couldn’t be tested for manageable reasons while fear of social stigma and emotional stress continued to be important barriers, especially in societies like ours. Given the important implications of genetic testing and its availability and affordability, reaching out to untested high-risk patients raises an ethical and professional dilemma that needs to be addressed from the physician, patients, and insurance perspectives.

Citation Format: Faris Tamimi, Baha’ sharaf, Osama Salama, Sarah Edaily, Suhaib Khater, Mais AlKyam, Lama Abujamous, Khansa Azzam, Hala Abu-Fares, Haneen Abaza, Hikmat Abdel-Razeq. Challenges and Dilemmas Following a Traceback Approach for Genetic Counseling and Genetic Testing for Pathogenic Germline Mutations among High-Risk Patients Previously Diagnosed with Breast Cancer [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 P6-02-02.