ObjectivesLocally 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). MethodsWe studied patients diagnosed primarily with LABC (n = 45). Pathologic and clinical responses were determined. Pathology slides were reviewed. ResultsOf 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-negative (ER-)/progesterone receptor-negative (PR-) 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. ConclusionsThe present study examined practical issues related to the classification and management of LABC 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. KEY WORDSBreast cancer, residual disease, pathology, endpoints, locally advanced disease

21160 Background: LABC poses a difficult clinical challenge . The correlation of complete clinical (cCR) and pathological response rates (pCR) based on molecular tumor characteristics with outcome is of great clinical interest. Methods: We conducted a retrospective chart review on consecutive patients diagnosed with LABC who completed NC between 2001–2006 at UC. Pathological response was classified as pCR (no invasive tumor in breast and axillary lymph nodes), RDLN (disease in lymph nodes), RDB( disease in breast), and RDBLN (disease in both). Overall survival (OS)and event free survival (EFS) were calculated using Kaplan-Meier analysis. Result: We included 45 patients. Median age 51, 40% (n=18) white and 60% (n=27) African American, Stage IIB 9%, IIIA 29%, IIIB 51 % and IIIC 11%. 75 % invasive ductal, 9% invasive lobular and 16% inflammatory breast cancer (IBC). ER+/or PR+ in 47% (18% ER + / PR +, 27% ER +/PR -, 2% ER-/PR+), and 53% ER -/PR-. HER2 neu + ( IHC 3 + or FISH ratio > 2.2) was identified in 27% of patients. NC regimens included: doxorubicin or epirubicine plus taxane (paclitaxel or docetaxel) 80 %, anthracycline only 10%, single agent taxane 4%, and 6% other regimens (2 CMF, 1 capecitabine). One patient received NC with trastuzumab. Response to NC was as follows: Clinically, 55% (n=25) achieved cCR, 38% partial clinical response, 4% stable disease and 2% progressive disease. Pathpogically, pCR was achieved in 22% (n=10) of all patients, 7% pPRLN, 24% pPRB and 47% RDBLN . None of the patients with IBC had pCR. Among ER+ and or PR + tumors , 19% achieved pCR compared to pCR of 25% among ER-/PR-. Among HER2 neu +, 17% achieved pCR compared to 25% in HER2 neu -. Among all patients who achieved cCR, only 36% actually had pCR. For patients who did not achieve pCR, OS and EFS were 5.7 years and 19 months respectively compared to both not yet reached for those with pCR. Conclusion: LABC has poor prognosis overall using standard chemotherapy. Clinical response followingNC was not well predictive of pathological response. ER-/PR - tumors respond better to neoadjuvant chemotherapy compared to ER+/orPR+ tumors. Less than 20% of HER2 neu + tumors achieve pCR before trastuzumab's routine use. More research is urgently needed to optimize treatment strategies and improve outcome of LABC and IBC. No significant financial relationships to disclose.

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.