miRNAs as radio‐response biomarkers for breast cancer stem cells

In breast cancer (BC), the presence of cancer stem cells (CSCs) has been related to relapse, metastasis, and radioresistance. Radiotherapy (RT) is an extended BC treatment, but is not always effective. CSCs have several mechanisms of radioresistance in place, and some miRNAs are involved in the cellular response to ionizing radiation (IR). Here, we studied how IR affects the expression of miRNAs related to stemness in different molecular BC subtypes. Exposition of BC cells to radiation doses of 2, 4, or 6 Gy affected their phenotype, functional characteristics, pluripotency gene expression, and in vivo tumorigenic capacity. This held true for various molecular subtypes of BC cells (classified by ER, PR and HER‐2 status), and for BC cells either plated in monolayer, or being in suspension as mammospheres. However, the effect of IR on the expression of eight stemness‐ and radioresistance‐related miRNAs (miR‐210, miR‐10b, miR‐182, miR‐142, miR‐221, miR‐21, miR‐93, miR‐15b) varied, depending on cell line subpopulation and clinicopathological features of BC patients. Therefore, clinicopathological features and, potentially also, chemotherapy regimen should be both taken into consideration, for determining a potential miRNA signature by liquid biopsy in BC patients treated with RT. Personalized and precision RT dosage regimes could improve the prognosis, treatment, and survival of BC patients. Breast cancer stem cells (BCSCs) have been related to relapse, metastasis, self‐renewal, and radioresistance. Ionizing radiation (IR) modifies miRNA expression. miRNAs related with BCSCs, tumorigenic process, radioresistance and poor prognosis showed variability in the expression according to IR dose, BC molecular subtypes and clinicopathological features. This miRNA signature could improve prognosis, treatments, and survival of BC patients by using precision radiotherapy dosage regimes.