52P Breast Cancer Stem Cells: A Novel Therapy for Breast Cancer

Abstract

ABSTRACT Simple BRCA screening is insufficient for ‘event-free survival’ as breast cancer is clinically and pathologically an extremely heterogeneous disease. Targeting breast cancer stem cells (BCSCs) present in bone marrow and breast tissues is an attractive alternative. Identification of BCSCs is the salient aspect of our research. 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 hinges upon identifying unique targets such as cell surface markers which will be decisive for the development of specific target therapies. A total of 10 early chemo-naive patients with biopsy-proven triple-negative metastatic breast cancer in age group 18-36 years (mean age 28 years) were selected randomly and tested for CD44/CD24 cell surface markers following immunosorting using a magnetic cell sorter and immunophenotyping by flow cytometric analysis. Isolated BCSCs were cultured for in vitro drug sensitivity towards platinum, anthracycline and docetaxel and correlation was drawn between cell differentiation, percentage of stem cells and drug response. Accordingly chemotherapy was designed for a particular patient. The percentage of BCSCs in pre- and post-chemotherapeutic conditions were further compared. We have detected BCSCs in 90% of the cases. Among positive samples, 89% of patients showed platinum sensitivity and the rest were found to be anthracycline sensitive. No sensitivity to docetaxel was observed. In lieu of this, cisplatin was applied in vivo and the percentage of BCSCs came down to 6.58% from an initial 11.16% (for a representative case). Thus the primary aim to target BCSCs at onset of tumors in breast cancer patients to control metastasis and relapse of disease was somewhat obtained. We further plan to correlate the ratio of selected markers present in patients in pre- and post-chemotherapeutic condition with time to recurrence, mortality, morbidity and progression-free survival. Finally, if no BCSCs were to prevail after chemotherapy, then patients would be kept under observation and if traces were found, we would proceed to stem cell replacement. Disclosure All authors have declared no conflicts of interest.