Aldehyde dehydrogenase 1A1 expression in breast cancer is associated with stage, triple negativity, and outcome to neoadjuvant chemotherapy.
Aldehyde dehydrogenase 1A1 expression in breast cancer is associated with stage, triple negativity, and outcome to neoadjuvant chemotherapy.
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DOI：
10.1038/modpathol.2011.172
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发表时间：
2012-03
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研究表明，ALDH1A1在乳房中的表达与较差的临床结果有关。ALDH1A1使环磷酰胺失活，环磷酰胺是乳腺癌化疗方案中不可或缺的药物。这项研究的目的是验证这些结果，将ALDH1A1的表达与环磷酰胺作为化疗(辅助或新辅助)一部分治疗的患者的临床结果相关联，并评估ALDH1A1作为预测乳腺癌亚型临床结果的有用标记物。共对513例原发性乳腺癌进行了研究。研究病例的组织芯片用ALDH1A1染色。获得关键的临床病理信息。计算无瘤生存期和总生存期。接受新辅助治疗的患者有大量残留癌症负担(RCB)，纳入研究。统计分析采用Fisher精确检验和Kaplan-Meier方法。ALDH1A1在53例(10%)患者中表达，三重阴性的表达频率较高，其次是HER2+，最后是激素受体+/HER2−(P<；0.0001)。晚期、结节阳性或较大的肿瘤与ALDH1A1的表达相关(分别为P=0.006、P<；0.0001和P=0.05)。在接受新辅助化疗的患者中，ALDH1A1的表达也与较差的无病生存期(P<；0.006)和总生存期(P<；0.01)相关。22例患者中有8例(36%)接受了新辅助化疗，最终死于疾病表达的ALDH1A1(P=0.008)。同样，在接受新辅助化疗并有肿瘤复发的23例患者中，8例(35%)表达该标志物(P=0.002)。复发风险是ALDH1A1阴性肿瘤的五倍。当环磷酰胺而不是曲妥珠单抗作为方案的一部分时，复发的风险增加了11倍。我们的结果与以前的研究是一致的。此外，我们发现ALDH1A1可能是一个有用的标记物，可以预测在RCB含量较高的新辅助治疗环境中化疗后较差的临床结果。然而，需要更大的队列来验证我们的结果。
Studies have shown that ALDH1A1 expression in the breast is associated with worse clinical outcome. ALDH1A1 inactivates cyclophosphamide, which is an integral agent in breast cancer chemotherapy regimens. The purposes of this study were to verify these results, to correlate ALDH1A1 expression with clinical outcome in patients treated with cyclophosphamide as part of the chemotherapy (adjuvant or neoadjuvant), and to evaluate ALDH1A1 as a useful marker to predict the clinical outcome of breast cancer subsets. A total of 513 primary breast cancers were studied. Tissue microarrays of the studied cases were stained with ALDH1A1. Key clinicopathological information was obtained. Disease-free survival and overall survival were calculated. Patients with neoadjuvant therapy who had substantial residual cancer burden (RCB) were included in the study. Fisher's exact test and Kaplan–Meier methods were used for statistical analysis. ALDH1A1 was expressed in 53 (10%) patients, with a higher frequency in triple negative, followed by HER2+, and finally hormonal receptor +/HER2− (P<0.0001). Tumors with advanced stage, node-positive, or larger tumor size were correlated with ALDH1A1 expression (P=0.006, P<0.0001, and P=0.05, respectively). ALDH1A1 expression was also correlated with worse disease-free survival (P<0.006) and overall survival (P<0.01) in patients who were treated with neoadjuvant chemotherapy. In all, 8 of 22 (36%) received neoadjuvant chemotherapy and died of disease-expressed ALDH1A1 (P=0.008). Similarly, 8 of 23 (35%) who received neoadjuvant chemotherapy and had tumor recurrence expressed this marker (P=0.002). The risk of recurrence was fivefold greater than negative ALDH1A1 tumors. The risk of recurrence became 11-fold greater when cyclophosphamide but not trastuzumab was part of the regimen. Our results are consistent with previous studies. Moreover, we found that ALDH1A1 could be a useful marker to predict worse clinical outcome after chemotherapy in the neoadjuvant setting with substantial RCB. However, a larger cohort is required to verify our results.
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影响因子：
12.3
作者：
Herschkowitz JI;Simin K;Weigman VJ;Mikaelian I;Usary J;Hu Z;Rasmussen KE;Jones LP;Assefnia S;Chandrasekharan S;Backlund MG;Yin Y;Khramtsov AI;Bastein R;Quackenbush J;Glazer RI;Brown PH;Green JE;Kopelovich L;Furth PA;Palazzo JP;Olopade OI;Bernard PS;Churchill GA;Van Dyke T;Perou CM
通讯作者：
Perou CM
影响因子：
4.8
作者：
Buess, Martin;Rajski, Michal;Rochlitz, Christoph
通讯作者：
Rochlitz, Christoph
影响因子：
45.3
作者：
Symmans, W. Fraser;Peintinger, Florentia;Pusztai, Lajos
通讯作者：
Pusztai, Lajos
影响因子：
158.5
作者：
Liu, Rui;Wang, Xinhao;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
11.5
作者：
Tanei, Tomonori;Morimoto, Koji;Noguchi, Shinzaburo
通讯作者：
Noguchi, Shinzaburo