Jacob, Kristina A.

Abstract Purpose: To improve the significance of insulin-like growth factor–binding protein 5 (IGFBP-5) as a prognostic and potentially predictive marker in patients with breast cancer. Experimental Design: Increased IGFBP-5 expression was identified in MCF-7 cells resistant (MCF-7R4) to the IGF-1R/insulin receptor (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 patients with breast cancer to examine correlative associations with invasive tumor fraction and outcome. The use 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, whereas IGFBP-5 overexpression in MCF-7 cells conferred resistance. When compared with 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, 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 patients with breast cancer. 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. Clin Cancer Res; 18(6); 1808–17. ©2012 AACR.

AbstractBackgroundThe feasibility, safety and outcomes of robotic presacral neurectomy were evaluated.MethodsA retrospective analysis was performed of 33 patients with midline chronic pelvic pain, who underwent robotic presacral neurectomy. Data were collected during the period March 2004–March 2010.ResultsAll patients underwent robotic presacral neurectomy and additional robotic procedures. Mean operating time for robotic presacral neurectomy was 5.8 (range 4.4–6.9) min. Mean blood loss, including concomitant procedures, was 39 (range 15–150) ml. Most patients were discharged the same day (60%) and mean hospital stay was 0.39 (range 0–2) days. There were no conversions or intra‐operative complications. There were two postoperative complications: one pelvic abscess and one Clostridium difficile colitis. Pain improvement was reported by 73% (22/30) of patients.ConclusionRobotic presacral neurectomy is safe and feasible, resulting in improvement of pelvic pain in selected patients. Copyright © 2011 John Wiley & Sons, Ltd.