Department of Obstetrics and Gynecology, University of Freiburg, Freiburg, Germany.
Oncol Rep. 2011 Oct;26(4):1037-45. doi: 10.3892/or.2011.1392. Epub 2011 Jul 15.
Alteration of gene expression profiles during chemotherapy may predict response to neoadjuvant chemotherapy (NAC) in breast cancer patients. In a prospective cohort study of 32 women with primary invasive breast cancer, we obtained tumor specimens before and after 4 cycles of NAC with epirubicine 90 mg/m2 and cyclophosphamide 600 mg/m2, followed by 4 cycles of docetaxel 100 mg/m2. Total-RNA was extracted from tumor specimens and the whole transcriptome was analyzed with Agilent's 44K single color microarray. Data analysis was performed by GeneSpring v.11 and IBM SPSS v.18. Ten tumors were classified as basal-like and 22 tumors were classified as non-basal-like. Gene expression-based molecular subtype (basal-like vs. non-basal-like) (P=0.003), but not tumor grade (P=0.07), estrogen receptor (P=0.1), progesterone receptor (P=0.6) and HER2 status (P=0.4) predicted pathological complete response to NAC. Specifically, 7/10 basal-like tumors responded to NAC, whereas 19/22 non-basal-like tumors did not respond. Comparing gene expression signatures before and after 4 cycles of NAC, we found that all patients with an initial non-basal-like tumor retained this tumor type, whereas 5/7 basal-like tumors, including all responders, lost this molecular subtype. Complete prediction of response to NAC was achieved with a 21 gene list (P=0.000008). Of note, both the expression and up-regulation of a single gene, i.e. HER4, predicted the response to NAC in 26/32 (81%; P=0.002) and in 23/25 (92%; P<0.001) patients, respectively. These preliminary data indicate that therapy-induced HER4 gene up-regulation may be associated with response to NAC with epirubicine, cyclophosphamide and docetaxel.
化疗过程中基因表达谱的改变可能预测乳腺癌患者新辅助化疗（NAC）的反应。在一项对 32 名原发性浸润性乳腺癌女性患者的前瞻性队列研究中，我们在接受表柔比星 90mg/m2 和环磷酰胺 600mg/m2 4 个周期的 NAC 以及随后的 4 个周期多西紫杉醇 100mg/m2 治疗前后获得了肿瘤标本。从肿瘤标本中提取总 RNA，并使用 Agilent 的 44K 单颜色微阵列分析整个转录组。数据分析使用 GeneSpring v.11 和 IBM SPSS v.18 进行。10 个肿瘤被分类为基底样，22 个肿瘤被分类为非基底样。基于基因表达的分子亚型（基底样与非基底样）（P=0.003），而不是肿瘤分级（P=0.07）、雌激素受体（P=0.1）、孕激素受体（P=0.6）和 HER2 状态（P=0.4）预测了对 NAC 的病理完全缓解。具体来说，7/10 个基底样肿瘤对 NAC 有反应，而 22/22 个非基底样肿瘤没有反应。比较 NAC 前 4 个周期前后的基因表达特征，我们发现所有初始非基底样肿瘤患者保留了这种肿瘤类型，而 5/7 个基底样肿瘤，包括所有应答者，失去了这种分子亚型。使用 21 个基因列表可以完全预测对 NAC 的反应（P=0.000008）。值得注意的是，单个基因即 HER4 的表达和上调都分别在 32 名患者中的 26 名（81%；P=0.002）和 23 名患者中的 25 名（92%；P<0.001）中预测了对 NAC 的反应。这些初步数据表明，HER4 基因的治疗诱导上调可能与表柔比星、环磷酰胺和多西紫杉醇的 NAC 反应相关。
