Background: The thymidine phosphorylase (TP) enzyme is expressed in higher levels in cancer tissue when compared with normal tissue. It is involved in the intratumoral activation of widely prescribed pyrimidine-derived antimetabolites such as 5'-deoxy-5-fluorouridine and capecitabine (Xeloda(®)). The purpose of this study was to determine the clinical correlation between TP expression in tumor tissue and the clinical outcome of capecitabine-based therapy in patients with locally advanced (stage III) or metastatic breast cancer (stage IV).
Methods: The following variables were analyzed as potential determinants of benefit from a capecitabine-based therapy: TP expression, estrogen receptor (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor-2 status, and Ki67 status. This was accomplished by immunohistochemical analysis of paraffin-embedded cancer tissues from 18 patients with breast cancer treated with at least one cycle of capecitabine. Clinical outcome was measured as time to progression.
Results: TP staining intensities in both the invasive and in situ components in patients with lobular and ductal carcinomas were reported. Higher levels of TP in the invasive component were expressed in ER-negative tumors when compared with ER-positive tumors (P<0.05). The ER-positive group expressing lower levels of TP had a median time to progression of 13 months compared with the ER-negative group expressing higher levels of TP which had a median time to progression of 7.5 months (P=0.14).
Conclusion: Patients with ER-positive tumors expressing lower levels of TP exhibit a longer time to progression when compared with patients with ER-negative tumors. Consequently, tumor TP expression does not seem to predict the outcome of capecitabine-based chemotherapy.
Keywords: metastatic breast cancer; prognostic significance; thymidine phosphorylase.