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Trastuzumab (T) has contributed to improving the prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Although some patients have been unresponsive or resistant to T. Loss of phosphatase and tensin homolog (PTEN) deleted on chromosome 10, PIK3CA mutation and p95HER2 expression have been reported to potentially be responsible for the poor response to T. This is a small-scale pilot study to be followed by a large-scale investigation examining the association between the biomarkers and clinical response. Based on the response to T, patients were divided into 3 groups in terms of progression-free survival (PFS): PFS &gt;8 months (group A, n=15), 3-8 months (group B, n=7) and PFS &lt;3 months (group C, n=11). PTEN protein expression was detected by immunohistochemistry and PIK3CA mutation by direct sequencing. The median age was 61, 60 and 47 years in groups A, B and C, respectively, with statistically significant differences among the groups. No additional patient background factors differed between the groups. A decreased PTEN expression (H score, &lt;100) was observed in 33.3 and 72.7% of patients in groups A and C, respectively. PTEN loss was slightly correlated with poor response to T. PIK3CA mutation frequency in exons 9/20 was 33.3% in group A and 27.3% in group C, with no significant correlation between PIK3CA mutation and clinical response. In this small-scale pilot study, a weak correlation was demonstrated between PTEN loss and poor response to T. This potential correlation is likely to be confirmed in the planned large-scale study, while the association of PIK3CA mutation and p95HER2 expression with poor response to T also requires examination.

molecular and clinical oncology

Evaluation of PTEN loss and PIK3CA mutations and their correlation with efficacy of trastuzumab treatment in HER2-positive metastatic breast cancer: A retrospective study (KBC-SG 1001)