Background/aim: Targeting the new and unique proteins is an important medical strategy for treating breast cancer. It is quite important to find out proteins that have a role in the development of cancer. Sirtuins (SIRT) are well related in different physiological activities and connected with cancer. We aimed to determine the effect of radiotherapy on SIRT1 and SIRT2, which have not been yet been clarified as a tumor suppressor or promoter. Materials and methods: Twenty-two women with nonmetastatic breast cancer enrolled in the study. Blood samples were taken before and after radiotherapy, soluble SIRT1 and SIRT2 levels were determined with ELISA kits. Results: There was no difference in SIRT1 levels before and after radiotherapy (p = 0.548). SIRT2 levels were significantly found to be decreased after radiotherapy (p = 0.042). There was a strong and positive correlation before radiotherapy (p < 0.001), and a moderate and positive correlation after radiotherapy (p = 0.007) between SIRT1 and SIRT2. Conclusion: These results suggest that SIRT2 may provide a new strategy for follow-up of breast cancer treatment. Additionally, by emphasizing the importance of SIRT2 in breast cancer, it opens ways to provide grounds for the development of the next generation of SIRT2-specific radiotracers. Finally, the most important thing, in fact, the positive correlation between SIRT1 and SIRT2 both before and after radiotherapy, appears to be clear evidence suggesting more oncogenic roles of sirtuins.