Abstract 104: Breast cancer stem cell extinction models: Implications for HER2 targeted therapy

Abstract

Abstract Treatment with trastuzumab therapy has been shown to dramatically improve survival and reduce recurrence of breast cancer in patients with overexpression of HER-2/neu. A subpopulation of cells in human breast tumors has been identified with characteristics of cancer stem cells. These breast cancer stem cells (BC SCs) have been recently shown to have increased expression of HER-2/neu, suggesting that BC SCs might have a chance of being eradicated with therapy targeting HER-2. We propose a mathematical model to examine the feasibility of eradicating breast cancer stem cells with HER-2 targeted therapy. Using a linear birth-death process model, we can predict the likelihood that BC SCs have become extinct after a year of trastuzumab therapy. We examine the effects of varying degrees of HER-2/neu overexpression and susceptibility of BC SCs to trastuzumab therapy by changing the death rates under targeted therapy (see Table). We also quantify the average time to extinction of BC SCs and the average number of BC SCs remaining after a year of therapy. We conclude that trastuzumab may be effective in eradicating BC SCs in the adjuvant therapy setting, even in patients in whom the bulk of the tumor population does not overexpress HER-2/neu.BC SC population size and extinction likelihood for varying death rates.Death rate (per week)Mean extinction time (SD) (weeks)Probability of extinction in 1 year (52 weeks)0.3433 (4.1)0.9990.3038 (4.6)0.9900.2841 (5.0)0.9720.2644 (5.4)0.9220.2448 (5.9)0.7950.2253 (6.5)0.5250.2059 (7.3)0.1640.2066 (8.2)0.0060.1676 (9.4)<0.0001 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 104.