Department of Medical Oncology, Oncology Institute, Istanbul University, Istanbul, Turkey.
Am J Clin Oncol. 2013 Jun;36(3):215-23. doi: 10.1097/COC.0b013e318243913f.
The primary aim of this study is to investigate the effect of change in the expression levels of survivin, glutathione-S-transferase P1 (GSTP1), and topoisomerase 2α (TOP2A) on the response to antracyclin-based and taxane-based neoadjuvant chemotherapy.
This study included 32 locally advanced breast cancer patients. Tumoral expressions of survivin, TOP2A, and GSTP1 in serial biopsy specimens obtained before treatment, after sequential 4 cycles of doxorubicin+cyclophosphomide, and 4 cycles of docetaxel were analyzed by real-time polymerase chain reaction. Survivin expressions were additionally analyzed in serial blood samples.
The pathologic complete response (pCR) rate and the overall response rate (clinical complete and partial) were 28% (n=9) and 91% (n=29), respectively. There were no statistically significant correlations between serial TOP2A expression levels and response. There was a nonsignificant trend toward an improved response rate with decreased survivin expression. A significant decrease in the GSTP1 expression level throughout treatment (P=0.014), which was also shown to be significantly correlated with a pCR (P=0.0001), was seen. Downregulation of GSTP1 after 4 cycles of anthracycline-based combination was independently associated with improved progression-free survival (P=0.01).
Downregulation of GSTP1 is a significant predictor of pCR and improved progression-free survival during anthracycline-based and taxane-based neoadjuvant chemotherapy in patients with locally advanced breast cancer.
本研究的主要目的是研究生存素、谷胱甘肽 S-转移酶 P1（GSTP1）和拓扑异构酶 2α（TOP2A）表达水平的变化对蒽环类和紫杉烷类新辅助化疗反应的影响。
本研究纳入 32 例局部晚期乳腺癌患者。采用实时聚合酶链反应分析治疗前、序贯多柔比星+环磷酰胺 4 周期和多西紫杉醇 4 周期后连续活检标本中生存素、TOP2A 和 GSTP1 的表达，并对连续血样中的生存素表达进行分析。
病理完全缓解（pCR）率和总缓解率（临床完全和部分）分别为 28%（n=9）和 91%（n=29）。TOP2A 表达水平与反应之间无统计学显著相关性。生存素表达降低与反应率提高呈无显著趋势。整个治疗过程中 GSTP1 表达水平显著降低（P=0.014），且与 pCR 显著相关（P=0.0001）。蒽环类联合化疗 4 周期后 GSTP1 下调与无进展生存期改善独立相关（P=0.01）。
在局部晚期乳腺癌患者接受蒽环类和紫杉烷类新辅助化疗过程中，GSTP1 下调是 pCR 和无进展生存期改善的重要预测因子。
