Bueno-de-Mesquita J M, Linn S C, Keijzer R, Wesseling J, Nuyten D S A, van Krimpen C, Meijers C, de Graaf P W, Bos M M E M, Hart A A M, Rutgers E J T, Peterse J L, Halfwerk H, de Groot R, Pronk A, Floore A N, Glas A M, Van't Veer L J, van de Vijver M J
Department of Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Breast Cancer Res Treat. 2009 Oct;117(3):483-95. doi: 10.1007/s10549-008-0191-2. Epub 2008 Sep 26.
The 70-gene prognosis signature (van't Veer et al., Nature 415(6871):530-536, 2002) may improve the selection of lymph node-negative breast cancer patients for adjuvant systemic therapy. Optimal validation of prognostic classifiers is of great importance and we therefore wished to evaluate the prognostic value of the 70-gene prognosis signature in a series of relatively recently diagnosed lymph node negative breast cancer patients.
We evaluated the 70-gene prognosis signature in an independent representative series of patients with invasive breast cancer (N = 123; <55 years; pT1-2N0; diagnosed between 1996 and 1999; median follow-up 5.8 years) by classifying these patients as having a good or poor prognosis signature. In addition, we updated the follow-up of the node-negative patients of the previously published validation-series (Van de Vijver et al., N Engl J Med 347(25):1999-2009, 2002; N = 151; median follow-up 10.2 years). The prognostic value of the 70-gene prognosis signature was compared with that of four commonly used clinicopathological risk indexes. The endpoints were distant metastasis (as first event) free percentage (DMFP) and overall survival (OS).
The 5-year OS was 82 +/- 5% in poor (48%) and 97 +/- 2% in good prognosis signature (52%) patients (HR 3.4; 95% CI 1.2-9.6; P = 0.021). The 5-years DMFP was 78 +/- 6% in poor and 98 +/- 2% in good prognosis signature patients (HR 5.7; 95% CI 1.6-20; P = 0.007). In the updated series (N = 151; 60% poor vs. 40% good), the 10-year OS was 51 +/- 5% and 94 +/- 3% (HR 10.7; 95% CI 3.9-30; P < 0.01), respectively. The DMFP was 50 +/- 6% in poor and 86 +/- 5% in good prognosis signature patients (HR 5.5; 95% CI 2.5-12; P < 0.01). In multivariate analysis, the prognosis signature was a strong independent prognostic factor in both series, outperforming the clinicopathological risk indexes.
The 70-gene prognosis signature is also an independent prognostic factor in node-negative breast cancer patients for women diagnosed in recent years.
70基因预后特征（范特·维尔等人，《自然》415(6871):530 - 536，2002年）可能有助于改进对淋巴结阴性乳腺癌患者进行辅助全身治疗的选择。预后分类器的最佳验证至关重要，因此我们希望在一系列相对近期诊断的淋巴结阴性乳腺癌患者中评估70基因预后特征的预后价值。
我们在一组独立的具有代表性的浸润性乳腺癌患者系列中（N = 123；年龄<55岁；pT1 - 2N0；1996年至1999年诊断；中位随访5.8年）评估70基因预后特征，将这些患者分类为具有良好或不良预后特征。此外，我们更新了先前发表的验证系列中淋巴结阴性患者的随访情况（范德维杰等人，《新英格兰医学杂志》347(25):1999 - 2009，2002年；N = 151；中位随访10.2年）。将70基因预后特征的预后价值与四个常用的临床病理风险指标进行比较。终点指标为无远处转移（作为首个事件）的百分比（DMFP）和总生存期（OS）。
预后不良（48%）患者的5年总生存率为82±5%，预后良好（52%）患者为97±2%（风险比3.4；95%置信区间1.2 - 9.6；P = 0.021）。预后不良患者的5年无远处转移生存率为78±6%，预后良好患者为98±2%（风险比5.7；95%置信区间1.6 - 20；P = 0.007）。在更新后的系列中（N = 151；60%预后不良 vs. 40%预后良好），10年总生存率分别为51±5%和94±3%（风险比10.7；95%置信区间3.9 - 30；P < 0.01）。预后不良患者的无远处转移生存率为50±6%，预后良好患者为86±5%（风险比5.5；95%置信区间2.5 - 12；P < 0.01）。在多变量分析中，预后特征在两个系列中都是强有力的独立预后因素，优于临床病理风险指标。
70基因预后特征也是近年来诊断的女性淋巴结阴性乳腺癌患者的独立预后因素。
