PREVALENCE OF BRCA1/2 PATHOGENIC VARIANTS AND THEIR ASSOCIATION WITH CLINICOPATHOLOGICAL FEATURES IN PATIENTS WITH TRIPLE NEGATIVE BREAST CANCER AT A TERTIARY CARE HOSPITAL IN KARACHI

Abstract

Background: Triple-negative breast cancer is a highly aggressive type of breast cancer in which the estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2) are not present. Clinically relevant identification of genetic and biochemical factors associated with disease aggressiveness is important due to the lack in targeted treatment options. Pathogenic mutations in BRCA1 and BRCA2 affect homologous recombination repair, may lead to genomic instability and contribute to oxidative stress, DNA damage and aggressive tumor behavior.

Objective: To determine the prevalence of BRCA1/2 pathogenic variants and evaluate their association with clinicopathological features and biochemical markers among patients with triple-negative breast cancer.

Methods: This cross-sectional analytical study was conducted from January 2024 to January 2025 at Tertiary Care Hospital in Karachi. Non-probability consecutive sampling was used to include 72 patients with triple-negative breast cancer whose cases were pathologically confirmed. Clinico-pathological parameters were noted such as age, menopausal status, family history, tumor size, tumor grade, tumor stage, lymph node status and ki-67 index. Samples of peripheral blood were taken for both the BRCA1/2 mutation and biochemical evaluation. Serum malondialdehyde, total antioxidant capacity, C-reactive protein, interleukin-6 and 8-hydroxy-2′-deoxyguanosine were determined. SPSS version 25 was used to analyze data. The analysis was performed using chi-square test, independent sample t-test and multivariate logistic regression. A p value <0.05 was declared to be statistically significant.

Results: Out of 72 patients, 20 patients (27.8%) were BRCA-positive, while 52 patients (72.2%) were BRCA-negative. BRCA1 pathogenic variants were more common than BRCA2 variants. BRCA positivity was significantly associated with positive family history, larger tumor size, grade III tumor, and advanced-stage disease. BRCA-positive patients showed significantly higher mean levels of malondialdehyde, C-reactive protein, interleukin-6, and 8-hydroxy-2′-deoxyguanosine, while total antioxidant capacity was lower compared with BRCA-negative patients. On logistic regression, positive family history, grade III tumor, advanced stage, raised malondialdehyde, and raised 8-hydroxy-2′-deoxyguanosine were independent predictors of BRCA1/2 mutation positivity.

Conclusion: BRCA1/2 pathogenic variants were identified in a considerable proportion of patients with triple-negative breast cancer. BRCA-positive status was associated with aggressive clinicopathological features and altered biochemical markers reflecting oxidative stress, inflammation, and DNA damage. Routine BRCA testing in triple-negative breast cancer patients may support genetic counseling, risk assessment, family screening, and personalized treatment planning.