Abstract LB-421: Diabetes pharmacotherapy: A potential modifier of breast cancer prognosis
Authors: Ceacareanu Alice C. , Hong Chi-Chen , Elgebaly Mostafa , Epstein Marie , Wintrob Zachary A. , Kossoff Ellen , Yeow David , Boateng Hans , Welt Jeffrey M. , Fu Hsin-Wei , Wightman Sarah , Forrest Alan 
Published: February 2011

Abstract
Breast cancer (BC) prognosis in patients with type 2 diabetes mellitus (T2DM) was never investigated from the perspective of their DM therapy. Further exploration is needed as our data evaluating 248 DM patients with newly diagnosed BC (1997-2006) show an increase in cancer-related mortality associated with use of insulin (I) or insulin secretagogues (IS) after 30 months median follow-up. The hazard ratio (HR) of a recurrence-free event among BC patients receiving IS only compared to those treated with only non-secretagogues (NS) was 2.6 in a Cox model analysis (table 1). Presented data were adjusted for collaborative stage, estrogen receptor status, age and race. Disease-free survival was measured by cancer recurrence or death from any cause.
These findings provide support for our hypothesis that use of I or IS for T2DM management in BC patients may lead to worsening of their cancer disease. Still, additional data investigating the extent of the insulin resistance and overall inflammation is needed.
We aimed to measure a panel of biomarkers related to inflammation and insulin resistance and to investigate whether the profiles identified for cases receiving NS drugs are associated with a better BC prognosis as compared to cases receiving I or IS for T2DM therapy. Proposed study will be conducted on 70 T2DM+BC and respectively 140 comorbidity-matched BC women, all previously enrolled in our retrospective study and being donors in the DataBank and BioRepository program. Serum biomarker profiles will be analyzed by multivariate modeling using log-rank or Cox proportional hazards regression to detect differences in disease-free survival and mortality.
We speculate that guiding T2DM therapy based on the baseline biomarker profile has the potential to improve recurrence and survival in BC patients. Findings consistent with this hypothesis will have direct and immediate applicability in BC care as screening and clinical intervention can be easily implemented.Table 1.Recurrence-free, disease-free, and overall mortality by Type II diabetes medication useMedication useNo. of eventsNo. at riskRecurrence-free survival aHR (95% CI)No. of eventsNo. at riskDisease-free free survival bHR (95% CI)No. of eventsNo. at riskOverall Mortality HR (95% CI)Non-secretagoguesNo974Ref1674Ref1475RefYes111700.53301700.83271710.91 (0.21, 1.30) (0.44, 1.55) (0.47, 1.79)Insulin secretagoguesNo8128Ref27128Ref24129RefYes121161.41191160.76171170.69 (0.54, 3.64) (0.40, 1.44) (0.35, 1.37)Non-secretagogues only585Ref1485Ref1285RefSecretagogues only6372.609372.297371.45 (0.63, 10.73) (0.78, 6.73) (0.44, 4.81)InsulinNo15188Ref31188Ref27189RefYes5561.1715561.4914571.61 (0.41, 3.30) (0.80, 2.80) (0.83, 3.12)Drug ClassesNone+NS only699Ref1799Ref1599Ref S only6372.719371.637371.18 (0.78, 9.52) (0.66, 4.05) (0.43, 3.30)S+NS3520.805520.585530.64 (0.19, 3.33) (0.21, 1.63) (0.22, 1.85)I+/−SorNS5561.3915561.4714571.50 (0.41, 4.66) (0.72, 2.99) (0.71, 3.18)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-421.