Association of radiological features with BRCA related genetic mutations: A ten year retrospective experience at Shaukat Khanum Memorial Hospital

Abstract

Background: Breast cancer is linked to BRCA1 and BRCA2 germline mutations represents a biologically aggressive subtype that is early in onset and heterogeneous on imaging. Even though mammography and ultrasound are still the most commonly used imaging modalities, local evidence evaluating the association between the radiological features and BRCA mutation status are scarce.

Objective: To evaluate the association between mammographic and sonographic imaging features and BRCA genetic mutation in histopathologically diagnosed breast cancer patients.

Methods: This retrospective observational study was conducted at Shaukat Khanum Memorial hospital within a period of ten years (January 2015- July 2025). 62 biopsy proven breast cancer patients with verified BRCA mutations were included. Next-generation sequencing was performed for genetic testing and variants were classified based on the American College of Medical Genetics and Genomics (ACMG) guidelines. Mammographic and ultrasound appearances such as lesion size, margins, laterality, lesion number, the existence of micro-calcifications as well as the axillary lymph node characteristics were analyzed. Statistical associations between imaging features and BRCA mutation status were assessed using SPSS version 25.

Results: The patients were all females with a mean age of 36.4 ± 7.4 years. 50.0% and 46.7% of patients were found to have BRCA1 and BRCA2 mutations respectively. The most common histopathological subtype was high-grade invasive ductal carcinoma (64.5%). Pleomorphic microcalcifications proved to be statistically significant with BRCA1 mutations (p = 0.05). There were no statistically significant associations between BRCA mutation status with laterality and lesion size, margins, multicentricity, laterality, or axillary lymph node characteristics.

Conclusion: The BRCA associated breast cancers are early in age and they are mostly of high-grade tumors. Most of the mammographic and sonograph appearances also overlap with the sporadic breast cancer, although the pleomorphic microcalcifications might indicate BRCA1-associated disease. Further studies based on the combination of radiology with clinical and pathological characteristics could provide enhanced genetic assessment and improved risk stratification in high-risk populations.

Keywords: BRCA mutations; Breast cancer; Mammography; Ultrasonography

Important Note:      Do mention Mehria Ahmad (Primary Author)  Nasreen Aman (corresponding Author)