Publication: Her2 pozitif metastatik meme kanserinde pten ekspresyon durumu ve trastuzumab direnci ile ilişkisi
Abstract
Trastuzumabın klinik yararlığının bilinmesine rağmen, intrinsik ya da kazanılmış direnç sık karşılaşılan klinik bir durumdur. Potansiyel bir direnç mekanizması, fosfataz ve tensin homologun (PTEN) kaybına bağlı olarak oluşan aberan aşağı doğru sinyal iletimidir. Bu çalışmanın amacı, metastatik meme kanserinde insan epidermal büyüme faktör reseptörü 2’ye (Her2) dönük verilen tedaviye yanıt ile PTEN kaybı arasında ilişki olup olmadığını değerlendirmektir. Her2 pozitif metastatik meme kanserli 38 hastada, PTEN’in immunohistokimyasal ekspresyonunu inceledik. İmmunohistokimyasal profiller ile klinik sonuç arasındaki ilişki değerlendirildi. Medyan yaş 50’ydi. Tam bilgi edinilen 38 hastanın, 6’sında (%15,8) PTEN kaybı gözlendi. Trastuzumab yanıtı ve PTEN ekspresyonları arasında, istatistiksel olarak anlamlı farklılık bulunmadı (p:0.538). PTEN ekspresyonları, HER2 pozitif metastatik meme kanserlilerde trastuzumab direncini öngörmek için değerlendirildi. Trastuzumab direnci ve bu biyobelirtecin ekspresyonları arasında, istatistiksel olarak anlamlı herhangi bir ilişki yoktu. PTEN kaybı sonucu tanımlanan PI3K yolağının aktivasyonu, metastatik meme kanserinde tedaviye yanıt ya da klinik sonuçlar ile ilişkili değildi. Sonuç olarak; PTEN kaybı olması, anti-HER2 tedaviden yarar sağlama potansiyeli olacak bu tür hastaları dışlamamalıdır. Meme kanseri; Her2; Trastuzumab; PTEN kaybı; PI3K yolağı
Despite clinical usefulness of trastuzumab, intrinsic or acquired resistance is a common clinical phenomenon. A potential mechanism of resistance includes aberrant downstream signaling caused by loss of phosphatase and tensin homolog (PTEN). The purpose of this study is to evaluate whether loss of PTEN is associated with response to anti-human epidermal growth factor receptor 2 (Her2) treatment in metastatic breast cancer (MBC). We analysed PTEN immunohistochemical expression in 38 Her2-positive metastatic breast cancer (MBC) treated with trastuzumab. The correlations between the immunohistochemical profiles and the clinical outcome were assessed. The median age was 50. PTEN loss was observed in 6 out of 38 informative cases (15.8 %). Statistically significant difference was not found between trastuzumab response and PTEN expressions (p:0.538). PTEN expressions were assessed on HER2 positive metastatic breast cancers for predicting trastuzumab resistance. There was no statistically significant correlations between trastuzumab resistance and the expressions of this biomarker. PI3K pathway activation, defined as PTEN loss, was not associated with response to treatment or clinical outcome in MBC. Finally, PTEN loss should not exclude patients from potentially beneficial anti-Her2 therapy. Breast cancer; Her2; Trastuzumab; PTEN loss; PI3K pathway
Despite clinical usefulness of trastuzumab, intrinsic or acquired resistance is a common clinical phenomenon. A potential mechanism of resistance includes aberrant downstream signaling caused by loss of phosphatase and tensin homolog (PTEN). The purpose of this study is to evaluate whether loss of PTEN is associated with response to anti-human epidermal growth factor receptor 2 (Her2) treatment in metastatic breast cancer (MBC). We analysed PTEN immunohistochemical expression in 38 Her2-positive metastatic breast cancer (MBC) treated with trastuzumab. The correlations between the immunohistochemical profiles and the clinical outcome were assessed. The median age was 50. PTEN loss was observed in 6 out of 38 informative cases (15.8 %). Statistically significant difference was not found between trastuzumab response and PTEN expressions (p:0.538). PTEN expressions were assessed on HER2 positive metastatic breast cancers for predicting trastuzumab resistance. There was no statistically significant correlations between trastuzumab resistance and the expressions of this biomarker. PI3K pathway activation, defined as PTEN loss, was not associated with response to treatment or clinical outcome in MBC. Finally, PTEN loss should not exclude patients from potentially beneficial anti-Her2 therapy. Breast cancer; Her2; Trastuzumab; PTEN loss; PI3K pathway