Department of Obstetrics and Gynecology, University Hospital, University of Heidelberg and National Center for Tumor Diseases, Voßstr. 9, 69115 Heidelberg, Germany.
Breast Cancer Res Treat. 2012 Apr;132(3):819-31. doi: 10.1007/s10549-011-1759-9. Epub 2011 Sep 30.
Overexpression of CD24 is an independent prognostic factor for breast cancer. Recently, two polymorphisms in the CD24 gene were linked to disease risk and progression in autoimmune diseases. Here, we evaluated the clinical relevance of these polymorphisms 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. A total of 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, multicenter, randomized phase II trial. CD24 polymorphisms were analyzed on germ line DNA and correlated with clinicopathologic variables and pCR. No significant associations were found between either of the polymorphisms and any of the clinicopathologic variables. In a multivariate analysis, CD24 Val/Val genotype was the only significant predictor of pCR (OR: 4.97; P = 0.003). The predictive potential was significant in both treatment arms and in the hormone receptor-positive subgroup. There was no correlation between CD24 3'UTR (TG/Del) genotype and pCR. We did not observe any association between CD24 genotype and CD24 protein expression or in vitro chemosensitivity, but there was a significant correlation between CD24 Val/Val and intratumoral lymphocyte aggregates. In conclusion, CD24 Ala/Val SNP is a strong and independent predictor of pCR after NCT for PBC and may affect immune functions rather than tumor characteristics. Further evaluation of the CD24 function and validation of its predictive potential are clearly warranted.
CD24 过表达是乳腺癌的独立预后因素。最近，CD24 基因中的两个多态性与自身免疫性疾病的疾病风险和进展相关。在这里，我们评估了这些多态性与预测原发性乳腺癌（PBC）新辅助化疗（NCT）病理完全缓解（pCR）的临床相关性，pCR 是该背景下最强的预后因素之一。共有 257 例患者被随机分配至多柔比星/环磷酰胺（AC）或多柔比星/培美曲塞（AP）方案，两种方案均随后给予多西他赛（Doc）作为 NCT，用于 T2-4 N0-2 M0 PBC，这是一项国际性、多中心、随机 II 期试验的一部分。在种系 DNA 上分析 CD24 多态性，并将其与临床病理变量和 pCR 相关联。未发现任何一种多态性与任何临床病理变量之间存在显著相关性。在多变量分析中，CD24 Val/Val 基因型是 pCR 的唯一显著预测因子（OR：4.97；P = 0.003）。在两种治疗组和激素受体阳性亚组中，预测潜力均具有显著性。CD24 3'UTR（TG/Del）基因型与 pCR 之间没有相关性。我们没有观察到 CD24 基因型与 CD24 蛋白表达或体外化疗敏感性之间存在任何关联，但 CD24 Val/Val 与肿瘤内淋巴细胞聚集之间存在显著相关性。总之，CD24 Ala/Val SNP 是 PBC 接受 NCT 后 pCR 的一个强而独立的预测因子，可能影响免疫功能而非肿瘤特征。显然需要进一步评估 CD24 功能及其预测潜力的验证。
