Background/aim: The PMS2 gene was evaluated for its role in the pathogenesis of breast cancer by analyzing its expression in blood samples obtained from healthy postmenopausal women, newly diagnosed breast cancer patients, and the same patients following surgical and therapeutic treatment. Materials and Methods: A total of 47 blood samples were analyzed, including 7 from healthy controls, 20 from newly diagnosed breast cancer patients (disease group), and 20 from the same patients’ post- treatment (cure group, 4 months’ post-surgery or therapy). RNA extraction, cDNA synthesis, and RT-PCR analysis were performed on blood samples to determine the expression levels of the PMS2 gene across groups, providing insight into the genetic changes associated with breast cancer progression and the impact of clinical interventions. SPSS was used for statistical analysis, including correlation and paired-sample t-tests. Results: PMS2 expression exhibited a highly significant difference between group 1 (healthy control), which showed no expression, and group 2 (disease group), which demonstrated upregulation of the PMS2 gene (P < 0.001, paired sample t-test) with a 99% confidence interval. A downregulation of gene expression was observed in group 3 (cure group) after treatment, and the comparison between the disease and cure groups revealed a statistically significant difference (P = 0.042, paired t-test) with a 95% confidence interval. The majority of patients aged 50–60 were diagnosed with stage 2 invasive ductal carcinoma. This systematic regulation of PMS2 expression highlights its role in disease development, progression, and therapeutic response. Conclusion: The data confirmed the involvement of the PMS2 gene in breast cancer aggressiveness and progression.