Department for Biomedical Research, University of Bern, Murtenstrasse, 40, 3008, Bern, Switzerland.
RECETOX, Faculty of Science, Masaryk University, Brno, Czech Republic.
BMC Cancer. 2019 Jun 7;19(1):549. doi: 10.1186/s12885-019-5752-8.
Breast cancer is a leading cause of cancer-related death in women worldwide. Despite extensive studies in all areas of basic, clinical and applied research, accurate prognosis remains elusive, thus leading to overtreatment of many patients. Diagnosis could be improved by introducing multigene molecular scores in standard clinical practice. Several tests that work with formalin-fixed tissue have become routine. Molecular scores usually include several genes representing processes, response to oestrogens, progestogens and human epidermal growth factor receptor 2 (Her2), respectively, which are combined additively in single values. These multi-gene scores have the advantage of being more robust and reproducible than single-gene scores. Their utility may be further enhanced by combining them with classical diagnostic parameters. Here, we present an exploratory study comparing the RISK and research versions of Oncotype DX recurrence score (RS), Prosigna Risk of Recurrence (ROR) and EndoPredict (EP) with respect to their prognostic potential for ipsilateral recurrence and/or distant relapse in brain, and we compared the scores to the intrinsic subtypes based on PAM50.
RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue cores of primary tumours, local recurrences and brain metastases. Gene expression was measured on a NanoString nCounter Analysis System. Intrinsic subtypes and molecular scores were computed according to published literature and RISK, RS, ROR and EP were compared against each other and to the intrinsic subtypes Luminal A (lumA), Luminal B (lumB), Her2-enriched (Her2↑), Basal-like (basal), and Normal-like (normal) of PAM50. Local recurrences and brain metastases were compared to their corresponding primary tumours.
All four molecular scores were highly correlated. Highest correlations were observed among genes related to proliferation while lower correlations were found among oestrogen-related genes. The scores were significantly higher in primary tumours progressing to brain metastases as compared to recurrence-free primary tumours and primary tumours that relapsed as local recurrences.
RISK and ROR-P are prognostic for primary tumours metastasizing to the brain. All four scores, RISK, RS, EP and ROR-P failed to discriminate between primary tumours that remained recurrence-free and primary tumours relapsing as local recurrences.
乳腺癌是全球女性癌症相关死亡的主要原因。尽管在基础、临床和应用研究的各个领域进行了广泛的研究，但仍难以准确预测预后，从而导致许多患者过度治疗。通过在标准临床实践中引入多基因分子评分，可以改善诊断。几种使用福尔马林固定组织的测试已成为常规。分子评分通常包括分别代表过程、对雌激素、孕激素和人表皮生长因子受体 2（Her2）的反应的几个基因，这些基因分别以加性方式组合成单个值。与单基因评分相比，这些多基因评分具有更稳健和可重复的优势。通过将它们与经典诊断参数结合使用，其效用可能会进一步提高。在这里，我们进行了一项探索性研究，比较了 Oncotype DX 复发评分（RS）、Prosigna 复发风险（ROR）和 EndoPredict（EP）的 RISK 和研究版本，以评估它们对同侧复发和/或脑远处复发的预后潜力，并将这些评分与基于 PAM50 的内在亚型进行比较。
从原发性肿瘤、局部复发和脑转移的福尔马林固定、石蜡包埋（FFPE）组织芯中提取 RNA。在 NanoString nCounter 分析系统上测量基因表达。根据已发表的文献计算内在亚型和分子评分，并将 RISK、RS、ROR 和 EP 相互比较，并与 PAM50 的 Luminal A（lumA）、Luminal B（lumB）、Her2 富集（Her2↑）、基底样（basal）和正常样（normal）内在亚型进行比较。将局部复发和脑转移与相应的原发性肿瘤进行比较。
所有四个分子评分高度相关。与增殖相关的基因相关性最高，而与雌激素相关的基因相关性较低。与无复发原发性肿瘤和局部复发的原发性肿瘤相比，进展为脑转移的原发性肿瘤的评分明显更高。
RISK 和 ROR-P 对转移到大脑的原发性肿瘤具有预后意义。所有四个评分（RISK、RS、EP 和 ROR-P）均未能区分无复发的原发性肿瘤和局部复发的原发性肿瘤。
