LAUSR

We would like to thank Dr. Kawada’s interest on our article and we are sincerely grateful to the important contributions [1, 2]. As expressed by Dr. Kawada, one important concern is that the absolute irisin levels found in patients with BC in the study performed by Esawy et al. and the absolute irisin levels in our study were different from each other. However, the units of irisin levels in both studies are different [3]. While irisin levels were expressed as pg/mL in our study, irisin levels were expressed as μg/mL in the study by Esawy et al. In addition, currently used ELISA kits are designed for research purposes and they are not verified to be used for diagnostic purposes. The sensitivity and specificity of ELISA kits obtained from different commercial companies may be different, therefore, it is possible that there is a difference between absolute values. Similar problems apply to different analytes, as well. In the study by Kinn Rod et al. four commercially available ELISA kits used for serum corticosterone measurement were compared. Eventually, they reported that the corticosterone levels obtained with the Arbor Assays and the DRG-4164 kits in the same blood samples were statistically significantly higher than the corticosterone levels of the DRG-5186 and the Enzo kits [4]. Developing ELISA kits with high sensitivity and specificity for serum irisin measurement or high-sensitivity methods that will enable the determination of irisin levels by high-pressure liquid chromatography (HPLC) or LC-MS/ MS (Tandem MS) methods will help to overcome this kind of problems. Another issue is the uncertainty of the effects of ursolic acid supplementation and resistance exercise on irisin levels, and Dr. Kawada stated that the effects of ursolic acid and resistance training interactions on irisin levels and some myokine levels should be investigated. This recommendation is really crucial for the researchers who plan to study on irisin. Supplements or exercise types that cause metabolic interactions that affect serum irisin levels would be one of the most important criteria for patient inclusion or exclusion. For this reason, we excluded individuals who do heavy exercise and use supplements, and we mentioned this in the method section. Also, it is stated in the letter that changes in myokine parameters with one intervention cannot clarify the mechanism of BC incidence and prognosis. There may be many variables that can affect the level of myokines, such as irisin released from the muscles, and longitudinal molecular studies are needed to determine these variables. Studies similar to the work of Kim et al. will make very important inputs to the elucidation of the effects of myokines such as irisin on cancer cells [5]. However, in our study, we determined whether the possible change in irisin level can be used to differentiate patients with muscle-invasive and non-muscleinvasive BC. Lastly, researchers determined that irisin levels decreased in cancer patients in a recent review [6].