The impact of neoadjuvant chemotherapy on the tumour microenvironment and the expression of stem cell properties in breast cancer cells
20 September 2018 (online)
Breast cancer is the most common malignancy in woman worldwide. Although treatment options have been improved over the past decade, metastases and recurrences still cause significant mortality. Major mechanisms for metastases are epithelial-mesenchymal transition (EMT) as well as development of stem cell features. The presence of disseminated tumour cells (DTCs) in the bone marrow of breast cancer patients is strongly linked to the development of metastases. Dormant DTCs have been reported to be chemoresistant, but mechanisms for their resistance to current treatments is as of yet poorly understood. One emerging line of research into treatment resistant breast cancer cells is elevated notch signalling. Here, we aim to assess the direct impact of neoadjuvant chemotherapy on the development of stem cell properties in breast cancer cells.
Methods and materials:
We examine EMT-markers (E-Cadherin), stem cell markers (CD133) as well as Notch4 on DTCs of 60 breast cancer patients (n = 30 patients who received primary systemic chemotherapy as well as n = 30 patients with primary surgical treatment). Expression of these markers will be analyzed by immunohistochemistry. Quantification of marker expression will be assessed according to the immunreactive score (IRS) by Remmele and Stegner.
Expression of these markers of patients treated with primary chemotherapy and patients treated with primary surgical treatment will be compared and analyzed with regard to disease progression and clinical parameters.
Stem cell features have been linked to therapy resistance and metastases. In this study, we aim to assess the impact of neoadjuvant chemotherapy on stem cell properties.