ABCB1 rs1128503 Polymorphism as a Potential Prognostic Marker in Breast Cancer: Associations with Tumor Progression and Survival Outcomes

Background and Objectives Breast cancer (BC) is a biologically heterogeneous disease with diverse molecular subtypes and clinical outcomes, strongly influenced by genetic factors. ATP-binding cassette (ABC) transporters play an important role in transmembrane processes, including drug efflux, cellular detoxification, and the maintenance of intracellular homeostasis. Variants in genes such as ABCB1 and ABCB8 may contribute to interindividual differences in tumor behavior, influencing clinicopathological characteristics and potentially affecting disease progression and treatment response. This study evaluated the association of two single nucleotide polymorphisms (SNPs), ABCB1 rs1128503 and ABCB8 rs56198402, with BC clinicopathological features. The findings aim to clarify their role in tumor biology and assess their potential as prognostic biomarkers, contributing to a better understanding of the genetic background of BC heterogeneity. Material and Method The study population comprised 170 female patients with histopathologically confirmed early-stage primary BC, aged 30 to 74 years (median age: 46 years). Clinical and tumor pathomorphological data, including tumor size, lymph node involvement, presence of metastases, degree of differentiation, estrogen (ER) and progesterone (PR) receptor status, human epidermal growth factor receptor 2 (HER2) status, disease progression, and mortality, were obtained from oncologists and the follow-up period extended until November 30, 2024. Genomic DNA was extracted from peripheral blood leukocytes using a column-based commercial DNA isolation kit in accordance with the manufacturer’s instructions. Genotyping of ABCB1 rs1128503 and ABCB8 rs56198402 was performed using TaqMan probe-based assays on the QuantStudio™ 3 Real-Time PCR System. The strength of associations between SNPs and BC clinicopathological characteristics was estimated using crude odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Survival outcomes were assessed using Kaplan-Meier analysis. Statistical analysis was conducted using IBM SPSS Statistics, version 30.0.0.0, and a p-value < 0.05 was considered statistically significant. The study protocol was approved by the Kaunas Regional Biomedical Research Ethics Committee (approval numbers BE-2-10 and P1-BE-2-10/2014). Results Significant associations were identified between ABCB1 rs1128503 and PR status, metastatic disease, disease progression, and mortality. Specifically, GA genotype carriers had higher odds of progesterone receptor positivity than GG (OR=2.038; 95% CI 1.016–4.091; p=0.045), which was corroborated by allele-based analysis, showing similarly increased odds among A allele carriers (OR=1.986; 95% CI 1.034–3.816; p=0.039). Conversely, GA carriers demonstrated reduced odds of metastasis (OR=0.301; 95% CI 0.122–0.742; p=0.009), disease progression (OR=0.387; 95% CI 0.171–0.877; p=0.023), and mortality (OR=0.361; 95% CI 0.144–0.907; p=0.030). Furthermore, tumor size and lymph node involvement were also significantly associated (p-value < 0.05) with the studied genotype, indicating a protective effect against more advanced disease features. A significant difference in progression-free survival was observed across ABCB1 rs1128503 genotypes, with the GA genotype associated with more favorable outcomes (p-value < 0.05). No significant associations were found between the ABCB8 rs56198402 and clinicopathological characteristics of BC. Conclusions and Recommendations The ABCB1 rs1128503 was significantly associated with several breast cancer clinicopathological features, including progesterone receptor status, metastasis, disease progression, and progression-free survival, suggesting a potential protective effect of the GA genotype. In contrast, no significant associations were found for the ABCB8 rs56198402 variant. Further studies with larger cohorts are needed to confirm these findings and clarify the biological role of ABCB1 variants in breast cancer progression and prognosis.