The influence of breast cancer susceptibility genes on radiotherapy efficacy and adverse toxicities

Breast cancer is a prevalent malignancy, with 5%–7% of cases hereditary, attributed to susceptibility gene mutations. Radiotherapy is vital in its treatment, but current guidelines lack consideration for genetic status. This review explored the relationships between breast cancer susceptibility genes such as BRCA1/2, CHEK2, ATM, etc. and radiotherapy efficacy and adverse toxicity. Findings showed that BRCA1/2 mutations do not change the therapeutic index of radiotherapy. The impact of CHEK2 mutations on radiotherapy remains uncertain. For ATM, radiotherapy may still be appropriate despite conflicting evidence on efficacy. PALB2 mutation carriers can receive standard adjuvant radiotherapy, while data on BARD1 and radiotherapy are scarce. RAD51 mutations may enhance radiotherapy efficacy with tissue-specific side effects. TP53 mutations are linked to poor radiotherapy outcomes and increased toxicity, suggesting caution in using radiotherapy for related patients. PTEN mutations may decrease tumor response to radiotherapy while increasing normal tissue toxicity. The roles NF1, CDH1, and STK11 play in breast cancer radiotherapy need to be further studied. In summary, breast cancer susceptibility genes exert heterogeneous effects on radiotherapy, underscoring the clinical significance of personalized treatment tailored to genetic profiles.