Gene expression profiling spares early breast cancer patients from adjuvant therapy: derived and validated in two population-based cohorts.
Gene expression profiling spares early breast cancer patients from adjuvant therapy: derived and validated in two population-based cohorts.
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DOI：
10.1186/bcr1325
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Bergh J
中科院分区：
文献类型：
--
作者：
Pawitan Y;Bjöhle J;Amler L;Borg AL;Egyhazi S;Hall P;Han X;Holmberg L;Huang F;Klaar S;Liu ET;Miller L;Nordgren H;Ploner A;Sandelin K;Shaw PM;Smeds J;Skoog L;Wedrén S;Bergh J
乳腺癌辅助治疗可显着提高生存率，但过度治疗和治疗不足是主要问题。迄今为止，乳腺癌表达谱主要用于识别预后不良的女性作为辅助治疗的候选者，但尚未证明其对治疗预测的价值。我们获得了 159 名人群来源的乳腺癌患者的基因表达谱，并使用层次聚类来识别与预后和辅助治疗影响相关的特征，定义为 5 年内远处转移或死亡。使用 76 名接受治疗的瑞典人群、135 名未经治疗的瑞典人群和 78 名荷兰患者的独立数据集进行验证。定义了瑞典人群研究的纳入和排除标准。在 159 名患者中，发现了 64 个基因的子集，可以对预后良好和不良的患者进行最佳区分。分层聚类揭示了三个亚组：接受治疗效果良好的患者、未经治疗效果良好的患者以及未能从给定治疗中受益的患者。与 Elston-Ellis 组织学分级（2 级与 1 级和 3 级与 1 的优势比分别为 2.81 和 3.32；P = 0.24 和 0.16）、肿瘤分期相比，表达谱提供了显着更好的预后（优势比，4.19；P = 0.007）（乳腺癌终点优势比，10.64）。 （第 2 阶段与第 1 阶段和第 3 阶段与第 1 阶段的优势比，1.11 1.28； P = 0.83 和 0.68）和年龄（比值比，0.11；P = 0.55）。风险组是一致的，并在分别用于 211 名和 78 名患者的瑞典和荷兰独立数据集中得到验证。我们已经确定了对未经治疗和系统治疗的原发性乳腺癌患者均有效的歧视性基因表达特征，有可能使他们免于辅助治疗。
Adjuvant breast cancer therapy significantly improves survival, but overtreatment and undertreatment are major problems. Breast cancer expression profiling has so far mainly been used to identify women with a poor prognosis as candidates for adjuvant therapy but without demonstrated value for therapy prediction. We obtained the gene expression profiles of 159 population-derived breast cancer patients, and used hierarchical clustering to identify the signature associated with prognosis and impact of adjuvant therapies, defined as distant metastasis or death within 5 years. Independent datasets of 76 treated population-derived Swedish patients, 135 untreated population-derived Swedish patients and 78 Dutch patients were used for validation. The inclusion and exclusion criteria for the studies of population-derived Swedish patients were defined. Among the 159 patients, a subset of 64 genes was found to give an optimal separation of patients with good and poor outcomes. Hierarchical clustering revealed three subgroups: patients who did well with therapy, patients who did well without therapy, and patients that failed to benefit from given therapy. The expression profile gave significantly better prognostication (odds ratio, 4.19; P = 0.007) (breast cancer end-points odds ratio, 10.64) compared with the Elston–Ellis histological grading (odds ratio of grade 2 vs 1 and grade 3 vs 1, 2.81 and 3.32 respectively; P = 0.24 and 0.16), tumor stage (odds ratio of stage 2 vs 1 and stage 3 vs 1, 1.11 and 1.28; P = 0.83 and 0.68) and age (odds ratio, 0.11; P = 0.55). The risk groups were consistent and validated in the independent Swedish and Dutch data sets used with 211 and 78 patients, respectively. We have identified discriminatory gene expression signatures working both on untreated and systematically treated primary breast cancer patients with the potential to spare them from adjuvant therapy.
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影响因子：
4.7
作者：
Lindahl, T;Landberg, G;Bergh, J
通讯作者：
Bergh, J
影响因子：
82.9
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HOLMBERG, L
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45.3
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45.3
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