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

Breast cancer (BC) is the most commonly diagnosed cancer among women worldwide. Klotho is an anti-aging protein implicated in tumor suppression; however, the relationship between circulating Klotho levels and BC remains unclear. We measured serum Klotho by enzyme-linked immunosorbent assay (ELISA) in 372 participants: 166 patients with BC, 24 patients with ductal carcinoma in situ (DCIS), and 182 controls, and examined its relation to clinicopathological characteristics, including estrogen receptor (ER), progesterone receptor (PR), HER2 and lymph node status, body mass index (BMI), and insulin-like growth factor 1 (IGF-1). Serum Klotho levels were significantly higher in invasive BC and DCIS patients compared with controls (p = 0.003 and p = 0.001, respectively), whereas no significant difference was detected between invasive BC and DCIS. After adjustment for age, Klotho levels remained significantly higher in BC and DCIS patients than in controls. Klotho levels correlated positively with IGF-1 (p = 0.0043), but not with BMI, ER, PR, HER2, or lymph node status. These preliminary findings demonstrate an association between elevated circulating Klotho and BC, as well as a positive relationship between Klotho and IGF-1. Further studies using age-matched cohorts and diagnostic-performance analyses are required to determine whether circulating Klotho has clinical utility as a BC biomarker.