Department of Bioinformatics and Statistics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Breast Cancer Res Treat. 2010 Jan;119(1):119-26. doi: 10.1007/s10549-009-0499-6. Epub 2009 Aug 8.
ER, PR and HER2 status in breast cancer are important markers for the selection of drug therapy. By immunohistochemistry (IHC), three major breast cancer subtypes can be distinguished: Triple negative (TN(IHC)), HER2+(IHC) and Luminal(IHC) (ER+(IHC)/HER2-(IHC)). By using the intrinsic gene set defined by Hu et al. five molecular subtypes (Basal(mRNA), HER2+(mRNA), Luminal A(mRNA), Luminal B(mRNA) and Normal-like(mRNA)) can be defined. We studied the concordance between analogous subtypes and their prediction of response to neoadjuvant chemotherapy. We classified 195 breast tumors by both IHC and mRNA expression analysis of patients who received neoadjuvant treatment at the Netherlands Cancer institute for Stage II-III breast cancer between 2000 and 2007. The pathological complete remission (pCR) rate was used to assess chemotherapy response. The IHC and molecular subtypes showed high concordance with the exception of the HER2+(IHC) group. 60% of the HER2+(IHC) tumors were not classified as HER2+(mRNA). The HER2+(IHC)/Luminal A or B(mRNA) group had a low response rate to a trastuzumab-chemotherapy combination with a pCR rate of 8%, while the HER2+(mRNA) group had a pCR rate of 54%. The Luminal A(mRNA) and Luminal B(mRNA) groups showed similar degrees of response to chemotherapy. Neither the PR status nor the endocrine responsiveness index subdivided the ER+(IHC) tumors accurately into Luminal A(mRNA) and Luminal B(mRNA) groups. Molecular subtyping suggests the existence of a HER2+(IHC)/Luminal(mRNA) group that responds poorly to trastuzumab-based chemotherapy. For Luminal(IHC) and triple negative(IHC) tumors, further subdivision into molecular subgroups does not offer a clear advantage in treatment selection.
乳腺癌的 ER、PR 和 HER2 状态是药物治疗选择的重要标志物。通过免疫组织化学（IHC），可以区分三种主要的乳腺癌亚型：三阴性（TN（IHC））、HER2+（IHC）和 Luminal（IHC）（ER+（IHC）/HER2-（IHC））。通过使用 Hu 等人定义的内在基因集，可以定义五种分子亚型（基底（mRNA）、HER2+（mRNA）、Luminal A（mRNA）、Luminal B（mRNA）和正常样（mRNA））。我们研究了类似亚型之间的一致性及其对新辅助化疗反应的预测。我们对荷兰癌症研究所 2000 年至 2007 年间接受新辅助治疗的 II-III 期乳腺癌患者的 195 例乳腺癌肿瘤进行了 IHC 和 mRNA 表达分析分类。采用病理完全缓解（pCR）率评估化疗反应。除了 HER2+（IHC）组外，IHC 和分子亚型具有高度一致性。60%的 HER2+（IHC）肿瘤未被归类为 HER2+（mRNA）。HER2+（IHC）/Luminal A 或 B（mRNA）组对曲妥珠单抗联合化疗的反应率较低，pCR 率为 8%，而 HER2+（mRNA）组的 pCR 率为 54%。Luminal A（mRNA）和 Luminal B（mRNA）组对化疗的反应程度相似。PR 状态和内分泌反应指数都不能准确地将 ER+（IHC）肿瘤细分为 Luminal A（mRNA）和 Luminal B（mRNA）组。分子分型提示存在一种对曲妥珠单抗为基础的化疗反应不佳的 HER2+（IHC）/Luminal（mRNA）组。对于 Luminal（IHC）和三阴性（IHC）肿瘤，进一步细分为分子亚群在治疗选择方面没有明显优势。
