In well-differentiated HCCs (G1) hyperechoic enhancement in the arterial phase and hypoechoic demarcation in the late phase correlate to the diameter.

1104 Background: Studies have consistently shown a correlation between multifocal (MF) and multicentric (MC) breast cancers and the rate and extent of lymph node metastases, but the literature is divided on whether there is a corresponding impact on survival outcomes. In the absence of compelling evidence to dictate otherwise, the convention according to current TNM staging guidelines has been to stage and treat MF and MC cancers according to the diameter of the largest lesions, without taking other foci of disease into consideration. We evaluated a large single institution cohort of MF and MC breast cancers to determine their frequency, clinico-pathological characteristics and effect on survival outcomes. Methods: MF and MC were defined pathologically as more than one lesion in the same quadrant and more than one lesion in separate quadrants, respectively. Patients were categorized by presence or absence of MF or MC disease. Kaplan-Meier product limit method was used to calculate relapse-free survival (RFS), breast cancer-specific survival (BCSS) and overall survival (OS). Cox proportional hazards models were fit to determine independent associations of MF/MC disease with survival outcomes. Results: Out of 3924 patients, 942 (24%) had MF (n=695) or MC (n=247) disease. MF and MC disease was associated with higher T-stages (T2 26% vs. 21.6%; T3 7.4% vs. 2.3%, P<0.001), higher nuclear grade (grade 3 44% vs. 38.2%, P<0.001), lymphovascular invasion (26.2% vs. 19.3%, P<0.001) and lymph node metastases (43.1% vs. 27.3%, P<0.001). After a median follow up of 51 months, MC but not MF breast cancers were associated with significantly worse 5-year RFS (90% vs. 95%, P=0.02) and BCSS (95% vs. 97%, P=0.01), and a trend towards worse 5-year OS (92% vs. 93%, P=0.08). After controlling for other risk factors, multifocality and multicentricity did not have an independent impact on RFS, BCSS or OS. This was true for the subset of T1N0 breast cancers as well. Conclusions: MF and MC breast cancers occurred in 24% of the cases and were associated with poor prognostic factors, but they were not independent predictors of worse survival outcomes. Our findings support the current TNM staging system of using the diameter of the largest lesion to assign T-stage.

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e12002 Background: Mesothelin is an ideal tumor-associated marker for the development of targeted therapy due to its limited expression in normal tissues. Identify the frequency of mesothelin expression in triple negative breast cancer may lead the path to customize the drug development in this lack of effective targeted subgroup. The aim of this study was to evaluate mesothelin expression in triple-negative breast cancer (TNBC) and its correlation with survival outcomes. Methods: Mesothelin expression was completed using immunohistochemistry on formalin fixed paraffin tumor sections, and quantified by H-score. An H-score >10 was considered positive. Patient’s characteristics were compared by mesothelin expression. Kaplan-Meier product limit method was used to estimate survival outcomes. Cox proportional hazards models was used to adjust for patient and tumor characteristics. Results: Median age was 52 years. Of the 109 TNBC, 37 (34%) were positive for mesothelin expression. There were no differences on patient/tumor characteristics by mesothelin expression with the exception of high frequency of lymphovascular space invasion in mesothelin-negative tumors (P=0.03). At a median follow up of 75.8 months 20 (18.3%) had experienced a recurrence and 22 (20.2%) had died. Five-year progression-free survival was 87% and 92% in patients with mesothelin-positive and mesothelin-negative tumors (P=0.43), and 5-year overall survival was 85% and 91% patients with mesothelin-positive and mesothelin-negative tumors (P=0.57), respectively. Mesothelin expression was not independently associated with PFS or OS in TNBC after adjustment for other patient and disease characteristics including grade, pathologic stage, lymphovascular invasion, and adjuvant chemotherapy survival outcomes. Conclusions: There was mesothelin expression in 34% of TNBC. No significant differences in the clinical characteristics by mesothelin expression with the exception of high lymphovascular invasion in mesothelin-negative tumors. Mesothelin expression did not correlate with survival outcomes in TNBC.

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BACKGROUND: Statins are cholesterol-reducing agents that affect intracellular pathways associated with tumorigenesis and inflammation. Preclinical studies have demonstrated that statins have anti-tumor effects and epidemiological studies have suggested that the use of HMG-CoA-reductase inhibitors is associated with improved long-term outcomes among breast cancer patients. In this study we sought to evaluate the effect of statins in the pathologic complete response (pCR) and survival outcomes among breast cancer patients receiving neoadjuvant systemic chemotherapy (NST). METHODS: Retrospective study including patients diagnosed between 1995-2007 with invasive primary breast cancer. All patients received neoadjuvant systemic chemotherapy. Use of statins during NST was identified by review of medical records. We compared pCR rate, relapse-free survival (RFS), disease-specific survival (DSS) and overall survival (OS) between statin-users and non-users. pCR was defined as no evidence of invasive carcinoma in the breast and axillary lymph nodes at the time of surgery. Descriptive statistics and Cox proportional hazards model were used in the analyses. RESULTS: From the 1449 patients included, 74 (5.11%) were treated with statin during NST. Statin users were more likely to be older, overweight/obese and more likely to be also treated with beta-blockers or metformin. No differences in pCR were observed according to statin use (16.2% vs 17.6% p = 0.75). In the multivariable model, the use of statin was not an independent predictor of pCR. With 55 months of follow-up (415 recurrences and 359 deaths), the 5-year RFS was 82% in the statin-treated patients and 70% in the non-statin treated group (p = 0.03), no differences were seen in DSS or OS. Subset analyses according to tumor subtype demonstrated patients with hormone receptor-positive tumors treated with statins had better 5-year RFS (93% vs 76%; p = 0.01). In the multivariable model, no association was observed between statin use and outcome. CONCLUSIONS: In our cohort of patients, statin use during NST was not independently associated with pCR, RFS, DSS and OS. Further studies with larger number of statin-treated patients are warranted to clarify the role of HMG-CoA reductase inhibitors in the treatment of breast cancer patients. In addition future studies should evaluate the effect of prolonged statin use and take the different type of statin subtype into account. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-12-06.

559 Background: Recent national consensus guidelines regarding optimal margin width for the management of DCIS have been published; however, controversy remains for managing margins <2mm. The relationship between margin width and locoregional recurrence (LRR) was determined in a contemporary cohort of patients. Methods: 1504 patients with DCIS undergoing definitive breast conserving surgery from 1996 to 2010 were analyzed for clinical and pathologic characteristics from a prospectively managed comprehensive academic cancer center database. Cox proportional hazard models were used to examine the relationship between margin width (<2mm or ≥2mm) and LRR by adjuvant radiation therapy (RT). Patients with positive margins (n=11) were excluded. Results: Overall, 3.4% of patients had a LRR at a median follow-up of 8.7 years. Univariate analysis of age, family history, grade, tumor size, comedonecrosis, RT, adjuvant hormonal therapy, ER status, and margin width found younger age (< 40 yr, p=0.02), no RT (n=299, p=0.005), and margin width <2mm(n=138, p=0.005) to be associated with LRR. The association between margin width and LRR differed by adjuvant radiation therapy status (p=0.02 for the interaction). There was no statistical significant difference in LRR for patients with margins <2mm vs ≥2 mm who received RT, (10-year LRR 6.0% vs 3.2%, respectively; HR 1.5, 95% CI 0.5-4.2, p=0.48). For patients who did not receive RT (n=299), those with margins < 2 mm were significantly more likely to develop a LRR than those with margins ≥2mm (10-year LRR 35.7% vs. 4.6%, respectively; HR 7.2, 95%CI 2.6-19.4, p=0.0001). Conclusions: In patients with <2mm margins receiving adjuvant radiation therapy, there is no difference in locoregional recurrence when compared to patients with ≥2mm margins. Additional surgery for wider margins of resection are not routinely justified in this group of patients but should be obtained for patients with <2mm margins who forego radiotherapy.