Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes.
Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes.
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DOI：
10.1158/1078-0432.ccr-13-0799
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发表时间：
2013-10-01
期刊：
影响因子：
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通讯作者：
Ueno NT
中科院分区：
文献类型：
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作者：
Masuda H;Baggerly KA;Wang Y;Zhang Y;Gonzalez-Angulo AM;Meric-Bernstam F;Valero V;Lehmann BD;Pietenpol JA;Hortobagyi GN;Symmans WF;Ueno NT
Lehmann和Bauer等人报告的三阴性乳腺癌（TNBC）的7种亚型分类的临床相关性尚不清楚。我们通过基于TNBC亚型确定新辅助化疗后的病理完全缓解（pCR）率，研究了TNBC异质性的临床相关性。我们重新验证了Lehmann和Bauer等人的实验，使用来自公共数据集的Affyssoft CEL文件。我们将这些方法应用于146例TNBC患者的基因表达微阵列从2000年6月至2010年3月在我们的机构。其中，130人接受了标准的新辅助化疗，并有可评估的病理反应数据。我们通过亚型对TNBC样品进行分类，然后使用Fisher精确检验和逻辑回归模型将亚型和pCR状态相关联。我们还评估了生存率，并将这些亚型与PAM 50固有亚型和残余癌症负担（RCB）指数进行了比较。TNBC亚型和pCR状态显著相关（P=0.04379）。基底样1（BL 1）亚型的pCR率最高（52%）;基底样2（BL 2）和管腔雄激素受体（LAR）的pCR率最低（分别为0%和10%）。通过似然比检验，TNBC亚型是pCR状态的独立预测因子（P=0.022）。这些亚型比PAM 50内在亚型（基底细胞样与非基底细胞样）更好地预测pCR状态。通过7种亚型对TNBC进行分类可预测高pCR率与低pCR率。我们证实了TNBC的7个亚型的临床相关性。我们需要前瞻性验证pCR率差异是否转化为长期结局差异。7亚型分类可能会刺激TNBC患者的创新个性化药物策略。
The clinical relevancy of the 7-subtype classification of triple-negative breast cancer (TNBC) reported by Lehmann and Bauer et al is unknown. We investigated the clinical relevancy of TNBC heterogeneity by determining pathological complete response (pCR) rates after neoadjuvant chemotherapy, based on TNBC subtypes. We revalidated the Lehmann and Bauer et al. experiments using Affymetrix CEL files from public datasets. We applied these methods to 146 TNBC patients with gene expression microarrays obtained from June 2000 to March 2010 at our institution. Of those, 130 had received standard neoadjuvant chemotherapy and had evaluable pathological response data. We classified the TNBC samples by subtype, then correlated subtype and pCR status using Fisher’s exact test and a logistic regression model. We also assessed survival and compared the subtypes to PAM50 intrinsic subtypes and residual cancer burden (RCB) index. TNBC subtype and pCR status were significantly associated (P=0.04379). The basal-like 1 (BL1) subtype had the highest pCR rate (52%); basal-like 2 (BL2) and luminal androgen receptor (LAR) had the lowest (0% and 10%, respectively). TNBC subtype was an independent predictor of pCR status (P=0.022) by a likelihood ratio test. The subtypes better predicted pCR status than did the PAM50 intrinsic subtypes (basal-like vs non basal-like). Classifying TNBC by 7 subtypes predicts high vs. low pCR rate. We confirm the clinical relevancy of the 7 subtypes of TNBC. We need to prospectively validate whether the pCR rate differences translate into long-term outcome differences. The 7-subtype classification may spur innovative personalized medicine strategies for TNBC patients.