Chromosomal damage in breast cancer patients undergoing different radiotherapy schemes

Radiotherapy (RT) remains a cornerstone in breast cancer (BC) treatment. While RT is effective, exposure to surrounding healthy tissues can lead to chromosomal damage and potentially increase the risk of secondary cancers. This study investigated chromosomal damage in circulating lymphocytes of BC patients receiving different RT schemes: ultra-hypofractionation in five fractions (UHF) and moderate hypofractionation in either 10-15 fractions (MHF-low) or 20 fractions (MHF-high). We also aimed to investigate how RT parameters influence MN yields in lymphocytes of BC patients. Additionally, the in vitro chromosomal radiosensitivity of primary and second primary BC patients was evaluated.

Blood samples were collected pre- and post-RT from 182 primary and 50 second primary BC patients. Chromosomal damage was assessed in lymphocytes using the cytokinesis-block micronucleus (CBMN) assay. To evaluate chromosomal radiosensitivity, all blood samples were irradiated in vitro with 1 Gy of X-ray before performing the CBMN assay. Associations of MN yields with cancer type, RT scheme, lymph node irradiation, boost dose delivery, and irradiated body volume were analyzed using linear regression and linear mixed-effects models.

Our findings indicated no difference in MN yields between primary and second primary BC patients. MHF-high RT scheme was associated with the highest MN induction, while the UHF scheme resulted in the lowest. Additionally, increased chromosomal damage was correlated with higher total tumor doses, larger irradiated volumes, and lymph node irradiation. No significant difference in in vitro chromosomal radiosensitivity was observed between primary and second primary BC patients.

Shorter RT scheme with higher dose per fraction may mitigate cytogenetic damage in circulating lymphocytes, offering potential advantages in long-term safety profiles. In vitro chromosomal radiosensitivity, as assessed by CBMN assay is not a hallmark for second primary BC risk.