Association of age-adjusted serum insulin-like growth factor-1 with clinicopathological features and HER2 status in breast cancer

Abstract Background Insulin-like growth factor-1 (IGF-1) is a crucial mediator in mammary tumorigenesis. However, its specific associations with molecular subtypes and early invasive capabilities remain insufficiently characterized. This study evaluated the clinicopathological relevance of age-adjusted serum IGF-1 levels in breast cancer patients. Methods Clinical data and serum biomarkers were analyzed from 351 participants, comprising 190 healthy controls, 25 patients with benign breast lesions, and 136 patients with primary breast cancer. To eliminate age-related physiological bias, absolute IGF-1 concentrations were transformed into age-adjusted Z-scores. The associations between IGF-1 Z-scores and clinicopathological features were evaluated using non-parametric statistical methods. The independent association with human epidermal growth factor receptor 2 (HER2) positivity was evaluated using multivariable logistic regression and receiver operating characteristic (ROC) analyses. Results Age-adjusted IGF-1 levels demonstrated significant differences across diagnostic groups ( p = 0.047). Subgroup analyses revealed that elevated IGF-1 was associated with HER2-positive status ( p = 0.019) and smaller tumor dimensions (≤ 2 cm, p = 0.035). Multivariable logistic regression identified the IGF-1 Z-score as an independent factor associated with HER2 positivity (adjusted Odds Ratio = 1.99, 95% Confidence Interval [CI]: 1.08–3.67, p = 0.027), with a receiver operating characteristic (ROC) area under the curve (AUC) of 0.726 (95% CI: 0.584–0.852, p = 0.003). Conclusions Elevated age-adjusted serum IGF-1 is independently associated with HER2 positivity and smaller tumor size. These findings suggest a potential association between high systemic IGF-1 and early aggressive tumor phenotypes rather than late-stage volumetric bulk, offering clinical perspectives for risk stratification.