Predictive Role of Midtreatment Changes in Survivin, GSTP1, and Topoisomerase 2α Expressions for Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients With Locally Advanced Breast Cancer

Introduction: 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 2 alpha (TOP2A) on the response to antracyclin-based and taxane-based neoadjuvant chemotherapy. Methods: 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. Results: 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). Conclusions: Downregulation of GSTP1 is a significant predictor of pCR and improved progression-free survival during anthracyclinebased and taxane-based neoadjuvant chemotherapy in patients with locally advanced breast cancer.