Abstract P5-08-13: Alteration of sensitivity to chemotherapeutic agents in tamoxifen resistant estrogen receptor positive breast cancer

Abstract

Abstract Background: In the treatment of estrogen receptor (ER) positive recurrent breast cancer, sequential treatment with endocrine or chemotherapy is generally used. However, there is no indicator by which we can select the appropriate chemotherapeutic agent to the endocrine resistant breast cancer in the subsequent treatment. The purpose of this study is to examine whether a preceding endocrine therapy affects the sensitivity to subsequent chemotherapy in ER positive breast cancer cells. Materials and methods: Three ER positive breast cancer cell lines (T47D, MCF7, BT474) and their tamoxifen (TAM) resistant derivatives (T47D/T, MCF7/T, BT474/T) were established and analyzed for sensitivity to doxorubicin (DOX), 5FU and paclitaxel (PTX). The mRNA levels of factors related to drug sensitivity were analyzed by RT-PCR. Results: MCF7/T became more sensitive to DOX and 5FU compared with the parental MCF7. In addition, the apoptosis induced by 5FU was significantly increased in MCF7/T compared with the parental MCF7. On the other hand, no difference of sensitivity to chemotherapeutic agents was observed in T47D/T and BT474/T compared with their parental cell lines. In MCF7/T and T47D/T, the expressions of dihydropyrimidine dehydrogenase (DPD) were significantly decreased compared with those in the parental cell lines, while no difference was observed in the expression of thymidine synthase (TS). The expression of thymidine phosphorylase (TP) was decreased in MCF7/T. Conclusion: Our data demonstrate that the sensitivity to 5FU might be altered in a subset of ER positive breast cancer cells, and suggest a possibility that the sensitivity to the chemotherapeutic agents might be modified by the preceding endocrine therapy in ER positive breast cancer cells. We are analyzing drug sensitivity in tumor-bearing mouse model and the data are going to be presented in the meeting. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-08-13.