375P - Targeting Breast Cancer Stem Cells for Treatment Failure Cases of Late Stage Breast Cancer

Abstract

ABSTRACT Disclosure All authors have declared no conflicts of interest. Targeting breast cancer stem cells (BCSCs) present in bone marrow and breast tissues is an attractive alternative for ‘event-free survival’ in breast cancer as it is an extremely heterogeneous disease. The invasive and mesenchymal properties of BCSCs with CD44 + /CD24low/ALDH1+ phenotype has made them a promising target for eliminating the metastatic capacity of primary tumors. We hypothesize that the ability to therapeutically attack stem cells will be decisive for the development of specific target therapies. Ten chemo-failure late stage patients with biopsy-proven triple-negative metastatic breast cancer were selected randomly. Breast cancer cells were isolated from whole tumor and cultured for in vitro drug sensitivity towards platinum, anthracycline and docetaxel and correlation was drawn between cell differentiation and drug response. Accordingly chemotherapy was designed for a particular patient. BCSCs were also isolated from the whole tumor, cultured and chemotherapy was designed. We detected chemo-failure in 65% cases for whole cell chemo-predictive assays, while BCSCs isolated from those non-responders responded to chemotherapy. Among positive samples, 89% of patients showed platinum sensitivity and rest were found to be anthracycline sensitive. No sensitivity towards docetaxel was observed. In lieu of this, cisplatin was applied ex vivo and percentage of BCSCs came down to 6.58% from an initial 11.16% (for a representative case). Thus the primary aim to target BCSCs to control metastasis and relapse of disease was somewhat obtained. We further plan to correlate ratio of selected markers present in patients in pre- and post-chemotherapeutic condition with time to recurrence, mortality, morbidity and progression-free survival.