Abstract PO5-17-06: Prevalence of BRCA Mutations: A Predictive Model in a High-Risk Population of BC Patients at a Tertiary Care Center
Authors: Suleman Kausar , Al-Khatib Khalid , Haque Emaan , Hassan Tusneem El , Suwaidan Abdullah Al , Alaklabi Sabah , Twegieri Taher , AlSayed Adhar , Ajarim Dahish , Zahrani Meshari Al , Akhtar Syed Saad , Malik Osama Al , Hefdhi Amal Al , Khayal Wafa , Zughaibi Sitah Al , Tulbah Asma 
Published: May 2024

Background: Breast cancer (BC) is a prevalent cancer in Saudi Arabia, with the majority of cases being sporadic. However, 25-30% of cases are associated with hereditary factors. Germline BRCA mutations are the most common mutations linked to hereditary BC predisposition syndromes, with a reported frequency of up to 11% in Saudi Arabia. Methods: This retrospective cohort study was conducted at a single institution in Saudi Arabia. Medical records of BC cases were reviewed where BRCA testing was performed, typically in patients with triple negative BC, hormone-positive (HR+) BC in younger premenopausal patients under the age of 45, or those with a personal or family history of BC. Patients meeting these criteria were diagnosed and treated at a tertiary care center in Saudi Arabia,between 2018 and 2021. The association between BRCA positivity and proposed risk factors was evaluated using chi-square analysis. Multivariate analysis was performed using logistic regression to assess the association between independent significant risk factors and BRACA+. Results: 482 cases of breast cancer were reviewed, with 412 testing negative for mutations and an overall BRCA positivity rate of 13.7%. Among BRCA positive patients, 62% had a positive family history (p-value &lt; 0.001), and they tended to be younger, with a median age of 38 compared to BRCA negative patients with a median age of 42 (p-value = 0.01). Of the 469 female patients, 62 (13%) were BRCA positive, and of the 12 male patients, 3 (25%) were BRCA positive. Among the BRCA positive patients, 73% had BRCA1 mutations, and 26% had BRCA2 mutations. No patients with lobular BC tested positive for BRCA mutations. The odds ratio for BRCA positivity in triple negative BC was 3.6 (95% CI 2.1-6.2, p-value &lt; 0.001). The odds ratio for BRCA positivity in HR+ cases was 2.5 (95% CI 1.4-4.2, p-value = 0.001). In HR+ cases, 4.6% had BRCA1 mutations, and 5% had BRCA2 mutations. In ER- cases, 20% had BRCA1 mutations, and 1.2% had BRCA2 mutations. Multivariate analysis revealed that increasing the age of diagnosis by one year reduced the chance of having BRCA positivity by 5% (p-value = 0.009). Having a positive family history increased the risk of BRCA positivity with an OR of 8 (95% CI 4-15.8, p-value &lt; 0.001), and triple negative BC increased the risk of BRCA positivity with an OR of 4.1 (CI 2.2-7.5, p-value &lt; 0.001). The model performance was evaluated using an AUC of 0.80. Conclusion: This study highlights the high prevalence of BRCA mutations in a high-risk population of BC patients. The proposed predictive model identified younger age, triple negativity, and a positive family history as independent predictors, with an AUC of 0.8. The study's predictive model suggest that these factors may be useful in identifying patients who are at increased risk of carrying BRCA mutations and could benefit from genetic counseling and testing.

Citation Format: Kausar Suleman, Khalid Al-Khatib, Emaan Haque, Tusneem El Hassan, Abdullah Al Suwaidan, Sabah Alaklabi, Taher Twegieri, Adhar AlSayed, Dahish Ajarim, Meshari Al Zahrani, Syed Saad Akhtar, Osama Al Malik, Amal Al Hefdhi, Wafa Khayal, Sitah Al Zughaibi, Asma Tulbah. Prevalence of BRCA Mutations: A Predictive Model in a High-Risk Population of BC Patients at a Tertiary Care Center [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 PO5-17-06.