Purpose To improve the significance of insulin-like growth factor binding protein 5 (IGFBP-5) as a prognostic and potentially predictive marker in breast cancer patients. Experimental Design Increased IGFBP-5 expression was identified in MCF-7 cells resistant (MCF-7R4) to the IGF-1R/InsR inhibitor, BMS-536924 and its role examined by targeted knockdown and overexpression in multiple experimental models. Protein expression of IGFBP-5 was measured by immunohistochemistry in a cohort of 76 breast cancer patients to examine correlative associations with invasive tumor fraction and outcome. The utility of a combined IGFBP-5/IGFBP-4 (BPR) expression ratio was applied to predict anti-IGF-1R/InsR response in a panel of breast cancer lines and outcome in multiple breast tumor cohorts. Results IGFBP-5 knockdown decreased BMS-536924 resistance in MCF-7R4 cells, while IGFBP-5 overexpression in MCF-7 cells conferred resistance. When compared to pathologically normal reduction mammoplasty tissue, IGFBP-5 expression levels were upregulated in both invasive and histologically normal adjacent breast cancer tissue. In both univariate and multivariate modeling, metastasis-free survival (MFS), recurrence free survival (RFS), and overall survival (OS) were significantly associated with high IGFBP-5 expression. Prognostic power of IGFBP-5 was further increased with the addition of IGFBP-4 where tumors were ranked based upon IGFBP-5/IGFBP-4 expression ratio (BPR). Multiple breast cancer cohorts confirm that BPR (high vs. low) was a strong predictor of RFS and OS. Conclusion IGFBP-5 expression is a marker of poor outcome in breast cancer patients. An IGFBP-5/IGFBP-4 expression ratio may serve as a surrogate biomarker of IGF pathway activation and predict sensitivity to anti-IGF-1R-targeting.

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Rectal distention in patients with OAB symptoms significantly lowered bladder sensation volumes (normal desire, strong desire, and maximal capacity).