Relationship between radiosensitivity of peripheral blood lymphocytes, breast cancer cells, and breast cancer stem cells in patients with breast cancer

Abstract

Radiosensitivity (RS) is an important biological factor that may contribute to future radiotherapy individualization. However, a comprehensive metric that adequately captures the complexities of radiation sensitivity has not yet been proposed, and the survival fraction at 2 Gy (SF2) remains the prevailing gold standard. Considerable variability in radiation responses across different cell types, together with heterogeneity within neoplastic and normal cell populations, continues to complicate radiosensitivity assessment. This study aimed to investigate the relationship between the radiosensitivity of malignant and non-malignant cells, with particular emphasis on cancer stem cells (CSCs). Blood samples and tumor biopsy specimens were collected from 20 breast cancer patients. Radiosensitivity was evaluated using clonogenic survival assays in lymphocytes, breast cancer cells, and breast cancer stem cells, while DNA damage and repair kinetics in lymphocytes were assessed using the γH2AX assay. The results showed that the geometric mean measured 30 min after radiation exposure, as well as the residual double-strand breaks (DSBs) at 3 and 24 h in the γH2AX assay, were significantly correlated with lymphocyte SF2. These findings suggest that the γH2AX assay may provide complementary information to clonogenic survival assay. However, no significant correlation was observed between the radiosensitivity of lymphocytes and that of tumor cells or CSCs. Breast cancer stem cells exhibited slightly higher survival following irradiation compared with the corresponding tumor cells, indicating a trend toward increased radioresistance. The observed radiosensitivity patterns may provide preliminary biological insights, but they should not be interpreted as direct clinical predictors without validation in larger cohorts with treatment outcome data. Further studies incorporating larger cohorts and additional biological indicators are required to improve the prediction of radiation response and clarify their potential relevance for future individualized radiotherapy research.