Effect of HER2 Ile655Val polymorphism on the response to trastuzumab treatment in HER2-positive breast cancer patients

Introduction HER2-positive breast cancer (HPBC) occurs in 20–25% of breast cancer patients and is characterized by a poor prognosis. Trastuzumab is a key drug for treating HPBC; however, resistance to trastuzumab is challenging in patients. This study aimed to investigate the effect of HER2 Ile655Val polymorphism on trastuzumab response in HPBC patients. Materials and methods This retrospective study involved 125 HPBC patients receiving trastuzumab therapy. Patients were categorized based on treatment response and resistance. Genotyping of the HER2 rs1136201 (A > G) polymorphism was conducted using the polymerase chain reaction (PCR)–restriction fragment length polymorphism (RFLP) method. Statistical analyses, including chi-square, logistic regression, and Kaplan–Meier survival analysis, were performed to assess the associations between genotypes and treatment response, analyze genetic models, and calculate progression-free survival (PFS). Results Of the 125 patients, 67 were treatment responders, while 55 were non-responders. The HER2 rs1136201 polymorphism showed significant associations with treatment response and PFS. The frequency of the G allele in treatment-responder and non-responder HPBC patients was 10.3% and 22.2%, respectively. Patients with the Val/Ile or Val/Val genotype had significantly worse progression-free survival (PFS) than patients with the Ile/Ile genotype ( P = 0.019). Conclusion The study suggests that the rs1136201 polymorphism in the HER2 gene may predict trastuzumab response in HPBC. This finding could potentially be used for personalized treatment of HPBC and help improve the outcome of this group of patients. Further research, however, is warranted to validate these results and establish the utility of this polymorphism in trastuzumab responsiveness.