Predictive value of CD24 ala/val polymorphism for pathologic complete response to sequential anthracycline- and taxane-based neoadjuvant chemotherapy for primary breast cancer.

Abstract

543 Background: Cytoplasmic expression of CD24, a GPI-anchored glycoprotein, is a strong prognostic factor for breast cancer and many other solid tumors. Recently, two polymorphisms in the CD24 gene (rs8734, rs3838646) have been linked to disease risk and progression in multiple sclerosis (MS), systemic lupus erythematodes (SLE) as well as the risk and progression of chronic hepatitis B infection. This study was designed to evaluate the clinical relevance of these polymorphisms in breast cancer with respect to their potential to predict a pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) for primary breast cancer (PBC), one of the strongest prognostic factors in this setting. Methods: 257 patients were randomized to either doxorubicin/cyclophosphamide (AC) or doxorubicin/pemetrexed (AP) both followed by docetaxel (Doc) as NCT for T2-4 N0-2 M0 PBC as part of an international, multicentric, randomized phase II trial. Both CD24 polymorphisms were analyzed on germline DNA and correlated with clinicopathologic variables and pCR. Results: There were no significant associations between either polymorphism and any of the clinicopathologic variables. In a multivariate analysis of both treatment arms, CD24 Val/Val genotype (rs8734) was the only significant predictor of pCR (OR: 4.97; p = 0.003). A test for interaction between CD24 Ala/Val genotype and treatment was negative (p = 0.49) and the predictive potential of this SNP was significant in both treatment arms. There was no correlation between CD24 3′UTR (TG/Del) genotype and pCR. Data on associations between genotype and CD24 expression as well as tumor associated lymphocytes will be presented. Conclusions: The CD24 Ala/Val SNP is a strong and independent predictor of pCR after NCT for EBC. Further evaluation of this predictive marker is clearly warrented. No significant financial relationships to disclose.