Breast cancer and the role of p95HER2 in trastuzumab resistance

Aim: Trastuzumab, the HER2 oncogene targeting drug, shows remarkable clinical efficacy in HER2-amplified breast cancer patients. In spite of robust activity, some of the patients with HER2-positive breast cancers do not get the benefit because of the resistance to trastuzumab. Overexpression of p95HER2 (truncated HER2) is one of the molecular mechanisms of trastuzumab resistance. We aimed to investigate whether p95HER2 overexpressing breast cancers were resistant to trastuzumab. Materials and Methods: p95HER2 and HER2 expression was determined by real-time polimerase chain reaction (RT-PCR) analysis. HER2 protein expression and HER2 gene amplification was also determined by immunohistochemistry and chromogenic in situ hybridization. 80 formalin fixed paraffin-embedded (FFPE) breast cancer tumor tissue archieve materials were used to analyze all of the evaluations. According to clinical information of the cases, none of the cases had distant metastases in the initial diagnosis. HER2 positive cases underwent trastuzumab regimens with/without chemoterapy. Results: This study included 80 breast cancer cases. 39 cases were HER2 positive and had trastuzumab treatment. 11 (28,2%) of these 39 cases were trastuzumab resistance and 28 (71,8%) of 39 cases did not show trastuzumab resistance. 3 cases were exitus. p95HER2 mean ratio was 11,01±19.73 (0,41-5,89) on 11 cases which were trastuzumab resistant. p95HER2 mean ratio was 1,99±1.37 (0,51-6,63) on 28 cases without trastuzumab resistance. If p95HER2 ratio was low, there was no trastuzumab resistance. However, for every statement on which p95HER2 ratio was high, there was trastuzumab resistance (p=0,210 Mann Whitney test). Conclusion: p95HER2 was found to be correlated with trastuzumab resistance, but it was not a determinant of trastuzumab resistance alone. We suggest that p95HER2 is sensitive but not specific for prediction of the trastuzumab resistance.