Abstract PS3-03-24: Patterns and Prevalence of Pathogenic Germline Mutations Among Patients with Invasive Lobular Breast Cancer

Abstract Background: Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer after invasive ductal cancer (IDC). Previous studies have shown that 5-10% of all breast cancers are associated with cancer-predisposing germline mutation. The frequency of these mutations in ILC is scarce. Here, we report on the pattern and frequencies of germline genetic mutations among Arab patients with ILC. Methods: In this retrospective observational study, electronic medical records were reviewed for all breast cancer patients diagnosed at King Hussein Cancer Center (KHCC) from January 2016 to May 2024. Included patients had histologically confirmed ILC and underwent germline genetic testing using restricted or expanded panels. Descriptive analyses were performed, with categorical variables reported as percentages. Chi-squared and Fisher’s exact tests were used to compare proportions of categorical variables between patients with pathogenic or likely pathogenic (P/LP) mutations and those without, as well as between BRCA and non-BRCA patients. Results: Out of the 6,539 patients who met the inclusion criteria, 477 (7.3%) had pure ILC histology. The median age at diagnosis was 49 years and only 13% were ≥ 65 years. Except for 2, all were female. Most patients (95%) were ER-positive, 92% PR-positive and 91% HER2 negative. Multicentric disease was observed in 43% of patients, bilateral disease in 14%, and 19% presented with metastatic disease. A family history of breast cancer was reported in 39% of patients, including 25% who had a first-degree relative with the disease. The most common additional malignancy observed in these patients were breast cancer (9.2%), with colorectal and endometrial cancers each at 0.8%, and ovarian cancer in only one patient. Regarding genetic testing, 12.6% had limited gene panels and 87.4% had extended panels. Overall, 47 (9.9%) carried a P/LP variant, most frequently in BRCA2 (n = 25, 53.2%), followed by ATM and PALB2 (n = 6 each, 12.8%). BRCA1 pathogenic variant was detected in only one patient. BRCA1/2 mutations were significantly more common in patients younger than 40 years; 17.0% compared to only 4.2% in older patients, p < 0.001. Patients with P/LP variants presented at younger ages, had more frequent first-degree breast cancer family history (p < 0.001), and were more likely to undergo risk-reduction surgery (p < 0.001). Both male patients also carried P/LP variants. Conclusions: We found that many Jordanian patients with invasive lobular breast cancer had germline mutations, especially in BRCA2. Younger age at diagnosis and having a first-degree relative with breast cancer, were linked to a higher chance of having a pathogenic mutation. These results show the importance of genetic testing to guide preventive measures and treatment personalization. Larger future studies are needed to improve genetic testing guidelines and outcomes for these patients. Citation Format: H. Abdel-Razeq, F. Tamimi, B. Sharaf, S. Abdel-Razeq, O. El Khatib, A. Sharaf, H. Bani Hani, A. Al-Atary, L. El Saket, Y. Talab, H. Khalil, M. Harb, S. Yousef, A. Nofal, A. Alghrabli, M. Abunasser. Patterns and Prevalence of Pathogenic Germline Mutations Among Patients with Invasive Lobular Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-03-24.