Circulating α-Klotho Is Elevated in Breast Cancer and Positively Correlates with IGF-1

Breast cancer is the most diagnosed cancer among women worldwide. Klotho is a protein with well-established anti-aging and tumor-suppressive functions, including a documented role in cancer biology such as breast cancer. However, the role of circulating Klotho levels as a biomarker in breast cancer patients remains unclear. We examined serum Klotho in relation to breast cancer and clinicopathological factors, including estrogen receptor (ER), progesterone receptor (PR), HER2 status, lymph node involvement, and body mass index (BMI). A total of 372 individuals were analysed: breast cancer patients (n=166), ductal carcinoma in situ (DCIS, n=24), and controls (n=182). Serum Klotho was measured by enzyme-linked immunosorbent assay (ELISA); comparisons used nonparametric Kruskal-Wallis and Mann-Whitney U tests with Bonferroni correction. Klotho was higher in breast cancer patients than controls (p < 0.01), similar between invasive and in situ disease, and correlated positively with insulin-like growth factor 1 (IGF-1) (p < 0.01), but not with BMI, ER, PR, HER2, or lymph node invasion. These findings raise the possibility that the Klotho–IGF-1 correlation reflects a negative feedback mechanism, whereby IGF-1 may promote Klotho secretion while Klotho may in turn attenuate downstream IGF-1R signalling, a mechanism that warrants further investigation as a potential regulator of IGF-1-driven tumorigenesis.