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Locally advanced breast cancer (labc) poses a difficult clinical challenge with an overall poor long-term prognosis. The strength of the association between tumour characteristics, treatment response, and outcome is not well defined. In the present study, we attempted to gain further insight into labc by reviewing tumour characteristics of patients treated with neoadjuvant chemotherapy and by studying the association of those characteristics with outcome. We calculated the residual cancer burden (rcb) score obtained at surgery and attempted to study its correlation with event-free survival (efs) and overall survival (os). We studied patients diagnosed primarily with labc (n = 45). Pathologic and clinical responses were determined. Pathology slides were reviewed. Of the 45 study patients, 9% had stage iib disease, 29%, stage iiia, 51%, stage iiib, and 11%, stage iiic. Inflammatory breast cancer (ibc) was found in 16%. Pathologic complete response (pcr) was achieved in 22% of all patients. None of the patients with ibc achieved pcr. Patients with estrogen receptor&ndash, negative (er&minus, )/progesterone receptor&ndash, negative (pr&minus, ) tumours were more likely to achieve pcr than were those with er+/pr+ tumours. Among patients with tumours that overexpressed human epidermal growth factor receptor 2 (her2/neu), 17% achieved pcr as compared with 25% of patients with non-overexpressing tumours, only 1 patient had received trastuzumab. The rcb scores were calculated in 32 patients and ranged between 0 and 4.6. The present study examined practical issues related to the classification and management of labc and ibc. The rcb, defined from routine pathology materials, was easily quantifiable. It appears to be a better predictor than pcr of outcome following neoadjuvant chemotherapy in labc. Higher rcb scores were associated with lower efs and a lower rate of os. A continual quest for reliable predictive and correlative prognostic markers, and for better surrogate endpoints for outcome, is essential to advance our understanding of labc and to improve treatment outcomes.

21103 Background: Complete pathological response (pCR) has been considered a reliable endpoint to assess the benefit of NC. However, different pathological responses ranging from near complete response to resistance would likely indicate different prognostic groups. Method: We studied patients with locally advanced breast cancer (LABC) who received NC between 2001–2006 at the University of Cincinnati. Pathological response to therapy was evaluated. In addition, RCB was quantified according to MD Anderson RCB Calculator index that combines pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size). We examined the correlation between pCR, RCB, event-free survival (EFS) and over all survival (OS) by Cox regression analyses. Result: Pathological slides of 32 patients were analyzed. Median age 52, 38% white and 62% African American. Stage IIB 12% , Stage IIIA 19%, Stage IIIB 53% and Stage IIIC 16% . 72% invasive ducal, 6% invasive lobular and 22% inflammatory cancer. Forty seven percent of tumors were ER +/or PR+ , 53% ER-/PR-, 28% HER-2 /neu + ( IHC 3+ or FISH HER2 gene to chromosome 17 ration > 2.2). Tumor response was as follows: 22% (n=7) achieved pCR , RCB scores ranged between 0- 4.87. By univariate Cox regression analysis, RCB correlated with EFS {Hazard ratio (HR) 1.57 (95% CI 1.04–2.38), p-value 0.018}, and with OS {HR 1.74 (95% CI 0.91 -3.32), p value-0.09}. However, pCR did not seem to correlate with EFS {HR 0 .24 (95%CI 0.03 -1.86–2.38), p-value .172} or OS {HR 0.03 (95% CI 0–89),p value-0.40}. By multivariate Cox regression analysis, RCB was noted to be an independent predictive variable for EFS {HR 1.59 (95% CI 1.04–2.43), p value-0.033} while pCR was not {HR 0.90 (95% CI 0.52–1.57), p value-0.7. Conclusion: RCB was easily quantifiable and appears to be a better predictor of outcome following neoadjuvant chemotherapy in LABC compared to pCR. Higher RCB scores were associated with higher EFS and lower rate of OS. Prospective trials are needed to further evaluate the role of RCB as an endpoint following NC. No significant financial relationships to disclose.

In this paper we present a probabilistic approach for analyzing the dependence of crosstalk effects on input pattern correlations. In particular, we show that the effects of coupling between interconnections, in current VLSI ICs, are strongly dependent on the spatio-temporal correlations at the primary inputs. Consequently, a smaller fraction of the total number of nets poses true crosstalk problems and only that fraction should be considered at lower levels of abstraction. The analysis is carried out at the logic-level of abstraction, which provides efficient CPU run time and memory usage.