The impact of ROR1, BMI-1 expression and PIK3CA mutation on the prognosis of luminal breast cancer

Breast cancer (BC) remains one of the leading causes of cancer mortality among women. Luminal BC subtypes, which are characterized by the expression of hormone receptors, account for about 70 % of all breast cancer cases. However, despite sensitivity to endocrine therapy, some patients demonstrate disease progression, which is associated with the molecular features of the tumor. The study of prognostic markers such as ROR1, BMI-1, and PIK3CA mutation is essential for understanding the mechanisms of resistance to therapy and metastasis. The aim of the study was to evaluate the prognostic significance of ROR1, BMI-1 protein expression and PIK3CA gene mutation in patients with luminal BC, who received hormone therapy with aromatase inhibitors, as well as their impact on clinical outcomes, including 5-year relapse-free survival. Material and Methods. The study included 80 patients with primary resectable luminal Her2-negative breast cancer (T1–2N0–1M0). All patients received adjuvant hormonal therapy with aromatase inhibitors. The expression of ROR1, BMI-1, cyclin D1 (immunohistochemistry), and PIK3CA mutation (real-time polymerase chain reaction) were assessed in tumor tissue. Results. Positive ROR1 expression was detected in 57.5 % of cases, BMI-1 in 82.5 %, and cyclin D1 overexpression in 37.5 %. The PIK3CA mutation was identified in 30 % of patients. ROR1 expression was observed in 100 % of cases with the luminal B subtype (14 out of 14) and in 48 % of cases with the luminal A subtype (32 out of 66), p=0.001. Cyclin D1 overexpression was observed in 58.7 % of patients with ROR1 expression and in 8.8 % of patients without ROR1 expression, p<0.0001. A high level of ROR1 expression (-50 %) was associated with cyclin D1 overexpression in 100 % of cases, p=0.044. Similarly, a high level of BMI-1 expression (-50 %) was associated with cyclin D1 overexpression in 64.7 % of patients compared to 31.6 % in those with low expression, p=0.03. Patients with PIK3CA mutations demonstrated significantly lower 5-year disease-free survival (p=0.03); disease progression was observed in 29 % of cases with the mutation versus 13 % in those without it (p=0.07). Conclusion. The study confirms the significance of ROR1, BMI-1 and PIK3CA mutation as potential prognostic markers in patients with luminal breast cancer. The identified relationships with cyclin D1 and molecular subtypes emphasize their role in tumor progression. The data obtained can be used for further personalization of treatment, including combination approaches with PI3K inhibitors and hormonal therapy.