Relationship Between Netrin-1 Staining and Neoadjuvant Treatment Response in HER2-Positive Locally Advanced Breast Cancer.

Background: Netrin-1 is a laminin-related glycoprotein involved in embryonic development and cancer progression. In breast cancer, increased Netrin-1 expression has been associated with lymph node positivity, metastatic disease, and treatment resistance. Given its potential role in tumor aggressiveness and response to therapy, we aimed to investigate the relationship between Netrin-1 expression and neoadjuvant treatment response in HER2-positive breast cancer. Methods: A total of 90 patients were included in the study. Netrin-1 expression was evaluated immunohistochemically in formalin-fixed, paraffin-embedded tumor tissues retrieved from pathology archives. Netrin-1 expression was assessed using two scoring parameters: staining proportion and staining intensity. Patients were divided into two groups according to the netrin-1 staining intensity and strength. Clinicopathological features were compared statistically between groups. Results: Pathological responses after neoadjuvant treatment were compared according to Netrin-1 staining proportion and intensity, and no statistically significant differences were observed. Miller-Payne Grades 4-5 were more frequent in the high staining proportion and intensity groups; however, these differences were not statistically significant (p = 0.69 and p = 0.38, respectively). Univariate logistic regression identified Ki-67, hormone receptor status, and tumor dimension as factors associated with pathological complete response. These variables remained independently associated with pCR in multivariate binary logistic regression analysis. Conclusion: Netrin-1 expression was not associated with neoadjuvant treatment response in HER2-positive breast cancer. Nevertheless, considering its biological role and therapeutic relevance in multiple malignancies, further studies are warranted to clarify the predictive and therapeutic potential of Netrin-1.