344P - Association Between Insulin Resistance (Ir) and Pathologic Complete Response (Pcr) to Neoadjuvant Chemotherapy (Nac) Among No Diabetic Women with Localized Infiltrating Breast Cancer (Libc)

Abstract

ABSTRACT Aim: The IR has been associated with increased risk of breast cancer (BC) and as a poor prognostic factor for relapse and survival. There is a lack of prospective studies that have reviewed the impact of IR across the NAC time and the likelihood of pCR. We determined the association between IR by HOMA2 (homeostasis model assessment) and pCR in LIBC. Methods: It was a prospective cohort, multicenter study. From 2012 to 2013, 64 patients were enrolled. Metabolic syndrome (MS) diagnosis was made by ATP III criteria. Insulin and glucose were measured at baseline and every 3 weeks during NAC. The IR was calculated by HOMA2 –IR.® Cut off value to define IR: HOMA2 ≥1.9. pCR (breast + nodes) was defined as no residual IBC. Results: Median age was 49 years. Axillary nodes were involved in 37 (57.8%). cTNM stage was II 50 (78.1%) and III 14 (21.8%). pCR (full cohort) was 37.5%. pCR in luminal A/B-like, triple negative and HER2 was 15.6%, 61.1% and 57.1% respectively. 25% had MS at baseline and up to 40% (final evaluation). At baseline 29 (45.3%) had IR and in final 34 (53.1%) (p = 0.005). We observed a gradual and almost linear increase of IR during the NAC time (p = 0.019). The group without IR (baseline) had a higher likelihood of pCR (HR 3.1, 95% CI 1.3-7.3). In the pCR group the HOMA2 remained below or slightly above 1.9 and with no changes over time (p = 0.225). Inversely in the no pCR group the IR increased over time and almost with a linear trend (p = 0.013). In a repeated measures analysis of HOMA2 over NAC time in the three biological subgroups, differences were observed only in luminal-like (p = 0.044). Comparing quartiles (Q1-2 vs Q3-4), basal insulin (p =0.018) and basal HOMA2 (p = 0.032) were significantly associated with pCR. In an adjusted logistic regression analysis for pCR, the IR remained as an independent factor for pCR (p = 0.018). Conclusions: We found a strong association between the status of IR and the likelihood of pCR in neoadjuvant setting of BC. To our knowledge this is the first prospective study describing the natural history of IR across time of the NAC. The IR increased over time of the NAC and the pCR likelihood is inversely associated with IR. Our findings suggest that the increase in central adiposity during NAC time produces a greater insulin resistance and thereby a cell proliferative environment resulting in a lower response to NAC. Disclosure: All authors have declared no conflicts of interest.