Jacquemier Jocelyne, Charafe-Jauffret Emmanuelle, Monville Florence, Esterni Benjamin, Extra Jean Marc, Houvenaeghel Gilles, Xerri Luc, Bertucci François, Birnbaum Daniel
Département d'Oncologie Moléculaire Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, UMR891 Inserm, IFR137, 232 Bd sainte Marguerite Marseille, France.
Breast Cancer Res. 2009;11(2):R23. doi: 10.1186/bcr2249. Epub 2009 Apr 30.
Breast cancers are traditionally divided into hormone-receptor positive and negative cases. This classification helps to guide patient management. However, a subgroup of hormone-receptor positive patients relapse irrespective of hormonal therapy. Gene expression profiling has classified breast tumours into five major subtypes with significant different outcome. The two luminal subtypes, A and B, show high expression of ESR1, GATA3 and FOXA1 genes. Prognostic biomarkers for oestrogen receptor (ER)-positive cases include progesterone receptor (PR) and androgen receptor (AR), and proteins related to proliferation or apoptotic resistance. The aim of this study was to identify the best predictors of success of hormonal therapy.
By immunohistochemistry we studied 10 markers in a consecutive series of 832 cases of breast carcinoma treated at the Paoli-Calmettes Institute from 1990 to 2002 and deposited onto tissue microarrays (TMA). These markers were luminal-related markers ER, PR, AR, FOXA1 and GATA3 transcription factors, proliferation-related Ki67 and CCND1, ERBB2, anti-apoptotic BCL2 and P53. We also measured vascular peritumoural invasion (VPI), size, grade and lymph node involvement. For 143 cases, gene expression profiles were available. Adjuvant chemotherapy and hormonal therapy were given to high- and low-risk patients, respectively. The 162 events observed and taken into account were metastases.
Molecular expression of the 10 parameters and subtype with ER status were strongly correlated. Of the 67 luminal A cases of this series, 63 were ER-positive. Multivariate analyses showed the highly significant prognostic value of VPI (hazard ratio (HR) = 2.47), Ki67 (HR = 2.9), P53 (HR = 2.9) and GATA3 (HR = 0.5) for the 240 patients who received hormonal therapy.
A panel of three antibodies (Ki67, P53 and GATA3) associated with VPI can significantly improve the traditional prognosticators in predicting outcome for ER-positive breast cancer patients receiving hormonal therapy.
乳腺癌传统上分为激素受体阳性和阴性病例。这种分类有助于指导患者管理。然而，一部分激素受体阳性患者无论接受激素治疗与否都会复发。基因表达谱分析已将乳腺肿瘤分为五种主要亚型，其预后有显著差异。两种管腔亚型，即A型和B型，显示ESR1、GATA3和FOXA1基因的高表达。雌激素受体（ER）阳性病例的预后生物标志物包括孕激素受体（PR）、雄激素受体（AR）以及与增殖或抗凋亡相关的蛋白质。本研究的目的是确定激素治疗成功的最佳预测指标。
通过免疫组织化学，我们研究了1990年至2002年在保利 - 卡尔梅特研究所接受治疗并制成组织微阵列（TMA）的连续832例乳腺癌病例中的10种标志物。这些标志物是与管腔相关的标志物ER、PR、AR、FOXA1和GATA3转录因子、与增殖相关的Ki67和CCND1、ERBB2、抗凋亡的BCL2和P53。我们还测量了肿瘤周围血管浸润（VPI）、大小、分级和淋巴结受累情况。对于143例病例，可获得基因表达谱。高危和低危患者分别接受辅助化疗和激素治疗。观察并纳入分析的162个事件为转移情况。
10个参数的分子表达与ER状态的亚型密切相关。在该系列的67例管腔A型病例中，63例为ER阳性。多变量分析显示，对于接受激素治疗的240例患者，VPI（风险比（HR）= 2.47）、Ki67（HR = 2.9）、P53（HR = 2.9）和GATA3（HR = 0.5）具有高度显著的预后价值。
一组与VPI相关的三种抗体（Ki67、P53和GATA3）可显著改善传统预后指标，用于预测接受激素治疗的ER阳性乳腺癌患者的预后。
