Abstract P3-06-05: Expression of SPARC in human breast cancer and its predictive value in the GeparTrio neoadjuvant trial.

Abstract

Abstract Background: Secreted protein acidic and rich in cysteine (SPARC) is an albumin-binding protein and associated with poor prognosis in multiple cancers. The aim of this analysis was to determine the frequency of SPARC expression among different molecular breast cancer subtypes and to evaluate its predictive value for therapy response after neoadjuvant anthracycline/taxane based chemotherapy (CTX) in participants of the GeparTrio trial. Methods: We evaluated tumoral SPARC expression by immunohistochemistry on tissue microarrays (TMAs) constructed from formalin-fixed paraffin-embedded (FFPE) pre-treatment core biopsies from 667 patients (pts) of the GeparTrio trial. The details of the GeparTrio study design are described elsewhere (von Minckwitz, JNCI 2008). Cutoffs for SPARC expression were determined using the web-based software Cutoff Finder (http://molpath.charite.de/cutoff/). Results: SPARC protein expression was measurable by IHC on the TMAs and 176 (26.4 %) of 667 tumors were SPARC positive. SPARC expression was increased in pts with triple-negative breast cancer (TNBC) compared to hormone receptor or HER2 positive subtypes (p = 0.039). SPARC positivity was associated with an increased pCR rate in the overall population (p < 0.001). SPARC negative tumors had a pCR rate of 15%, which increased to 27% in SPARC positive tumors. Similarly, in TNBC the pCR rate increased from 26% in SPARC negative tumors to 47% in SPARC positive tumors (p = 0.032). In multivariate logistic regression analysis adjusted for standard clinicopathological factors, SPARC was independently predictive in the overall population (p = 0.010) as well as the subgroups of pts with TNBC (p = 0.036). Conclusions: SPARC is expressed in all biological breast cancer subtypes with TNBC revealing the highest expression rate. Our data suggest that SPARC expression may provide predictive information for response to neoadjuvant CTX. As SPARC is an albumin-binding protein and might mediate intratumoral accumulation of nab-Paclitaxel, prospective analysis of SPARC expression is planned in the GeparSepto trial. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-05.