Brouckaert Olivier, Pintens Saskia, Van Belle Vanya, Van Huffel Sabine, Camerlynck Edward, Amant Frédéric, Leunen Karin, Smeets An, Berteloot Patrick, Van Limbergen Erik, Decock Julie, Hendrickx Wouter, Weltens Caroline, Van den Bogaert Walter, Vanden Bempt Isabelle, Drijkoningen Maria, Paridaens Robert, Wildiers Hans, Vergote Ignace, Christiaens Marie-Rose, Neven Patrick
Multidisciplinary Breast Centre, UZLeuven, Leuven 3000, Belgium.
Breast Cancer Res Treat. 2009 May;115(2):349-58. doi: 10.1007/s10549-008-0110-6. Epub 2008 Jul 16.
Prognostic subgroup classification of operable breast cancers using cDNA clustering of breast cancer-related genes resembles the classification based on the combined immunohistochemical (IHC) expression of the hormone and HER-2 receptors. We here report the short-term disease-free interval (DFI) of operable breast cancers by their joint hormone receptor/HER-2 phenotype.
Short-term follow-up (FU) of a prospective cohort of 1,958 breast-cancer patients primary operated at our institution between 2000 and 2005. Receptors were evaluated using IHC. Steroid receptors were considered positive for any nuclear staining; HER-2 for strong (3+) membrane staining or positive fluorescence in situ hybridization (FISH). Kaplan-Meier (KM) DFI curves were calculated for any relapse defined as a local, regional, contralateral, or distant breast cancer event for the six predefined breast cancer subgroups: ER + PR + HER-2 - (PPN), ER + PR - HER-2 - (PNN), ER + PR + HER-2 + (PPP), ER - PR - HER-2 - (NNN), ER - PR - HER-2 + (NNP), and ER + PR - HER-2 + (PNP). P-values were calculated for comparison of the six different survival curves using two possible adaptations for multiple testing. A multivariate model for the receptors predicting DFI did incorporate local and systemic adjuvant therapy.
Median patient age was 57 years (ranges 26-96) and median FU was 3.35 years. Overall, DFI at median FU was 91%; 94% for PPN, 89% for PNN, 86% for NNN, 81% for PPP, 80% for PNP, and 76% for NNP cases. Some receptor subgroups had a significantly better DFI than others based on multiple testing, especially when the PPN group was compared against the four most frequent subtypes. The multivariate model with local and systemic adjuvant therapy confirmed the prognostic value of ER, PR, and HER-2 for short-term DFI.
It is possible to distinguish short-term prognostic breast cancer subgroups only on the basis of ER, PR, and HER-2 even when stratified for local and systemic adjuvant therapy. While gene expression profiles based on microarray data of over hundreds of genes will probably teach us much about breast cancer biology, heterogeneity, and prognosis, we emphasize the important short-term prognostic value of currently used IHC markers for ER, PR, and HER-2.
使用乳腺癌相关基因的cDNA聚类对可手术乳腺癌进行预后亚组分类，类似于基于激素和HER-2受体联合免疫组化（IHC）表达的分类。我们在此报告可手术乳腺癌按其联合激素受体/HER-2表型划分的短期无病间期（DFI）。
对2000年至2005年间在本机构接受初次手术的1958例乳腺癌患者的前瞻性队列进行短期随访（FU）。使用IHC评估受体。类固醇受体对于任何核染色均视为阳性；HER-2对于强（3+）膜染色或阳性荧光原位杂交（FISH）视为阳性。针对六个预定义的乳腺癌亚组，计算Kaplan-Meier（KM）DFI曲线，任何复发定义为局部、区域、对侧或远处乳腺癌事件，这六个亚组为：ER + PR + HER-2 - （PPN）、ER + PR - HER-2 - （PNN）、ER + PR + HER-2 + （PPP）、ER - PR - HER-2 - （NNN）、ER - PR - HER-2 + （NNP）和ER + PR - HER-2 + （PNP）。使用两种可能的多重检验校正方法计算六个不同生存曲线比较的P值。预测DFI的受体多变量模型纳入了局部和全身辅助治疗。
患者中位年龄为57岁（范围26 - 96岁），中位随访时间为3.35年。总体而言，中位随访时的DFI为91%；PPN组为94%，PNN组为89%，NNN组为86%，PPP组为81%，PNP组为80%，NNP组为76%。基于多重检验，一些受体亚组的DFI明显优于其他亚组，特别是当PPN组与四种最常见亚型进行比较时。包含局部和全身辅助治疗的多变量模型证实了ER、PR和HER-2对短期DFI的预后价值。
即使在根据局部和全身辅助治疗进行分层时，仅基于ER、PR和HER-2也有可能区分短期预后乳腺癌亚组。虽然基于数百个基因的微阵列数据的基因表达谱可能会让我们对乳腺癌生物学、异质性和预后有更多了解，但我们强调目前使用的ER、PR和HER-2的IHC标记物具有重要的短期预后价值。
