The Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK.
Ralph Lauren Centre for Breast Cancer Research, Royal Marsden Hospital, London, UK.
Breast Cancer Res. 2018 Sep 4;20(1):103. doi: 10.1186/s13058-018-1040-9.
Several prognostic signatures for early oestrogen receptor-positive (ER+) breast cancer have been established with a 10-year follow-up. We tested the hypothesis that signatures optimised for 0-5-year and 5-10-year follow-up separately are more prognostic than a single signature optimised for 10 years.
Genes previously identified as prognostic or associated with endocrine resistance were tested in publicly available microarray data set using Cox regression of 747 ER+/HER2- samples from post-menopausal patients treated with 5 years of endocrine therapy. RNA expression of the selected genes was assayed in primary ER+/HER2- tumours from 948 post-menopausal patients treated with 5 years of anastrozole or tamoxifen in the TransATAC cohort. Prognostic signatures for 0-10, 0-5 and 5-10 years were derived using a penalised Cox regression (elastic net). Signature comparison was performed with likelihood ratio statistics. Validation was done by a case-control (POLAR) study in 422 samples derived from a cohort of 1449.
Ninety-three genes were selected by the modelling of microarray data; 63 of these were significantly prognostic in TransATAC, most similarly across each time period. Contrary to our hypothesis, the derived early and late signatures were not significantly more prognostic than the 18-gene 10-year signature. The 18-gene 10-year signature was internally validated in the TransATAC validation set, showing prognostic information similar to that of Oncotype DX Recurrence Score, PAM50 risk of recurrence score, Breast Cancer Index and IHC4 (score based on four IHC markers), as well as in the external POLAR case-control set.
The derived 10-year signature predicts risk of metastasis in patients with ER+/HER2- breast cancer similar to commercial signatures. The hypothesis that early and late prognostic signatures are significantly more informative than a single signature was rejected.
已经建立了多个用于预测早期雌激素受体阳性（ER+）乳腺癌的预后标志物，随访时间为 10 年。我们检验了一个假设，即分别优化用于 0-5 年和 5-10 年随访的标志物比优化用于 10 年随访的单一标志物更具预后价值。
使用 Cox 回归分析对来自接受 5 年内分泌治疗的绝经后患者的 747 例 ER+/HER2-样本的公共微阵列数据集，测试了先前被确定为与预后相关或与内分泌耐药相关的基因。在 TransATAC 队列中，对接受 5 年阿那曲唑或他莫昔芬治疗的 948 例绝经后 ER+/HER2-患者的原发性 ER+/HER2-肿瘤进行了选定基因的 RNA 表达检测。使用惩罚性 Cox 回归（弹性网络）为 0-10 年、0-5 年和 5-10 年分别推导预后标志物。使用似然比统计进行了标志物比较。在来自 1449 例患者队列的 422 例样本的病例对照（POLAR）研究中进行了验证。
微阵列数据分析选择了 93 个基因；其中 63 个在 TransATAC 中具有显著的预后意义，在每个时间段内最为相似。与我们的假设相反，早期和晚期标志物并不比 18 基因 10 年标志物更具预后价值。18 基因 10 年标志物在 TransATAC 验证集中进行了内部验证，其预后信息与 Oncotype DX 复发评分、PAM50 复发风险评分、乳腺癌指数和 IHC4（基于四个 IHC 标志物的评分）相似，在外部 POLAR 病例对照集中也是如此。
所推导的 10 年标志物预测 ER+/HER2-乳腺癌患者转移风险的能力与商业标志物相似。早期和晚期预后标志物比单一标志物更具信息性的假设被拒绝。
