Abstract 475: Resection of primary tumor improves survival in mouse metastatic breast cancer model

Abstract

Abstract Introduction: Removal of the primary tumor is not currently standard treatment for metastatic breast cancer. It is thought that doing so would induce metastatic proliferation and death. However, multiple retrospective studies over the last decade suggest a possible survival benefit from primary tumor resection. The purpose of this study, therefore, is to evaluate the role of primary tumor resection in metastatic breast cancer using a mouse model. However, because there is no consensus on which model best mimics human breast cancer metastasis, the first objective is to compare the different mouse models. Then, using the best mouse model, the primary tumor in metastatic cancer is removed to evaluate the effect on metastatic progression and survival. Methods: The models evaluated include tail vein (TV), subcutaneous (SQ), percutaneous mammary (PM) and open mammary (OM) implantation of 4T1-luc2 cells,a luciferase transfected murine estrogen receptor negative breast cancer cell line. Tumor burden was quantified in vivo by measuring the photons emitted after injection of luciferin. After mice were diagnosed with metastatic breast cancer, they were prospectively randomized to two groups; primary tumor resection versus observation. Student's t-test and Kaplan-Meier survival statistical analysis were used. Results: TV produces a 50% tail tumor rate and SQ produces intradermal and intramuscular implamantation. When compared to other methods, OM provides the most reproducible method of implanting cells into the mammary fat pad. In addition, OM produces more cancer proliferation and invasion 4 days after implantation than the other methods. When compared to SQ, OM produces larger tumors (p<0.02) and greater mortality (40% versus 0% at 28 days). In addition, OM breast cancer cells in mice metastasize to the axillary lymph nodes prior to metastasizing to distant organs, similar to human breast cancer. Although OM takes slightly more time to perform than other methods, it is easy to learn even for the inexperienced. Resection of the primary tumor in metastatic breast cancer does not induce metastatic proliferation. In fact, primary tumor resection instead provides a significant survival benefit in mice, 100% mortality in the observation group at 46 days versus 80% mortality in the surgery group at 75 days (p<0.02). Conclusions: OM is the mouse model which best mimics human breast cancer metastasis. Reducing tumor burden by primary tumor resection provides a significant survival benefit in mice with metastatic breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 475.