Abstract P4-09-16: WAVE3 Over-Expression Is Associated with Adverse Tumor Characteristics and Mortality in Breast Cancer

Abstract

Abstract Background: WAVE3 regulates actin polymerization and subsequent cell migration leading to enhanced metastatic potential. Based on pilot data that suggested WAVE3 expression was associated with high histologic grade and absence of estrogen receptor (ER) expression we hypothesized that WAVE3 expression would correlate with ER status and tumor grade in a matched group of breast cancer (BC) patients. WAVE3 expression was alsoanalyzed in relation to adverse tumor characteristics, distant recurrence (DR) and BC specific mortality. Methods: Our institutional BC database was reviewed for patients who presented with, invasive BC from 1999-2009. Matching by stage and treatment was achieved for 61 patients with Scarff-Bloom-Richardson (SBR) grade 1 and ER+ tumors (SBR1/ER+) to 61 patients with SBR grade 3 and ER-tumors (SBR3/ER-). Cytosolic WAVE3 tumor expression was determined by immunohistochemistry. The product of stain intensity (0-3) and percentage of cells staining (0-100) was used to derive a WAVE3 score (0-300). The log rank test was utilized to compare BC specific mortality or distant recurrence free survival at various WAVE3 scores. A score of ≥212 was found to have the strongest association with poor outcome. The association between WAVE3 score and clinicopatholigic features, DR and BC specific mortality was assessed. Results: Increased frequency of Her2-neu (+) status, DR and BC specific mortality was noted in the SBR3/ER-group but WAVE3 score was no different between the two groups(Table1). In all 122 patients median WAVE3 score increased with tumor size (0.234, p=0.009), (+) lymph node status 200 vs. (-), 145, p =0.03, and stage (I, 160 vs. II,180 vs III, 240, p=0.012). There was no association between WAVE3 score and Her2-neu status(+200 vs. -180, p=0.51). In the SBR1/ER+ group only (+) lymph node status remained associated with WAVE3 score(+) 200 vs. (-) 130 (p=0.02). In the SBR3/ER-group only lymph node status lost association with WAVE3 score (+)180 vs.(-)170, (p=0.50). DR and BC specific survival could only be assessed in the SBR3/ER-group. Median WAVE3 score was elevated with DR (240 vs. none, 160, p=0.03) and BC specific mortality (270 vs. none 170, p=0.004). A WAVE3 score ≥212 was associated with distant recurrence and BC specific mortality on Kaplan Meier analysis (p=0.01) and P<0.001). On multivariate analysis a WAVE3 score ≥212 was associated with an increased risk for BC specific mortality (p=0.009). The association of DR and WAVE3 score ≥212 approached significance (p=0.068). Table 1 Conclusion: WAVE3 expression is not associated with tumor grade, and ER or Her2 neu status. WAVE3 is associated with tumor size, stage, DR and BC specific mortality in the high risk SBR3/ER-group. A WAVE3 score of ≥212 is associated with distant recurrence and breast cancer specific mortality on univariate analysis and BC specific mortality on uni-and multivariate analysis. WAVE3 expression may contribute to adverse outcome in high risk breast cancer patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-16.