ABSTRACT
PURPOSE: Topoisomerase II alpha (Topo II alpha) plays a role in DNA replication and is the molecular target for anthracyline-based chemotherapy. The purpose of this study was to evaluate the relationship between Topo II alpha expression and survival in patients with invasive breast cancer. METHODS AND MATERIALS: Formalin-fixed, paraffin-embedded tumor specimens from 24 women with invasive breast cancer were stained for Topo II alpha expression. All women underwent mastectomy. Radiotherapy was given at the University of Utah Department of Radiation Oncology. Of the patients, 23 (96%) received chemotherapy. The level of Topo II alpha expression within tumor cells was compared with clinical factors and overall survival. RESULTS: The median percentage of tumor cells expressing Topo II alpha was 70%. Increased Topo II alpha tumor expression significantly correlated with diminished disease-free survival. Five-year disease-free survival was 100% for patients with <70% of breast cancer cells expressing Topo II alpha compared with 42% for patients with > or =70% Topo II alpha expression (p = 0.008). The level of Topo II alpha expression within tumor cells correlated with T stage (p = 0.008) but not with other pathologic factors. CONCLUSIONS: Increased Topo II alpha expression significantly correlated with diminished disease-free survival in patients with invasive breast cancer. These findings may indicate a role for Topo II alpha expression as a prognostic factor in breast cancer.
Subject(s)
Antigens, Neoplasm/metabolism , Biomarkers, Tumor/metabolism , Breast Neoplasms/enzymology , Breast Neoplasms/mortality , DNA Topoisomerases, Type II/metabolism , DNA-Binding Proteins/metabolism , Adult , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Carcinoma, Ductal, Breast/enzymology , Carcinoma, Ductal, Breast/mortality , Carcinoma, Ductal, Breast/pathology , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Humans , Mastectomy , Radiotherapy, AdjuvantABSTRACT
PURPOSE: To evaluate the relationship between cyclooxygenase-2 (COX-2) expression and pathologic features and outcome in invasive breast cancer. METHODS AND MATERIALS: Formalin-fixed, paraffin-embedded tumor specimens from 23 women with invasive breast cancer were stained for COX-2 expression. All women underwent mastectomy and locoregional radiotherapy. The distribution (percentage of positive staining cells) and intensity of COX-2 expression within the tumor cells were compared with clinical factors, including stage, grade, lymph node involvement, and outcome. RESULTS: For invasive breast cancer, the distribution and intensity of COX-2 tumor expression correlated significantly with diminished overall survival. The 5-year overall survival rate was 100% for patients with <75% of breast cancer cells expressing COX-2 compared with 49% for patients with > or =75% (p = 0.044). The 5-year overall survival rate was 100% for patients with COX-2 intensity <80 compared with 60% for patients with COX-2 intensity > or =80 (p = 0.018). The percentage and intensity of COX-2 expression also correlated significantly with disease-free survival. The percentage of cells expressing COX-2 was significantly greater in women <40 years old than in women > or =40 years old (81% vs. 59%, respectively, p = 0.04). CONCLUSION: Both the distribution and the intensity of COX-2 expression correlated significantly with disease-free and overall survival in patients with invasive breast cancer. Younger patients with invasive breast cancer may have a greater percentage of COX-2 expression in their tumors.
