Department of Medicine I, Medical University of Vienna, Germany.
Clin Cancer Res. 2011 Sep 15;17(18):6012-20. doi: 10.1158/1078-0432.CCR-11-0926. Epub 2011 Aug 1.
According to current guidelines, molecular tests predicting the outcome of breast cancer patients can be used to assist in making treatment decisions after consideration of conventional markers. We developed and validated a gene expression signature predicting the likelihood of distant recurrence in patients with estrogen receptor (ER)-positive, HER2-negative breast cancer treated with adjuvant endocrine therapy.
RNA levels assessed by quantitative reverse transcriptase PCR in formalin-fixed, paraffin-embedded tumor tissue were used to calculate a risk score (Endopredict, EP) consisting of eight cancer-related and three reference genes. EP was combined with nodal status and tumor size into a comprehensive risk score, EPclin. Both prespecified risk scores including cutoff values to determine a risk group for each patient (low and high) were validated independently in patients from two large randomized phase III trials [Austrian Breast and Colorectal Cancer Study Group (ABCSG)-6: n = 378, ABCSG-8: n = 1,324].
In both validation cohorts, continuous EP was an independent predictor of distant recurrence in multivariate analysis (ABCSG-6: P = 0.010, ABCSG-8: P < 0.001). Combining Adjuvant!Online, quantitative ER, Ki67, and treatment with EP yielded a prognostic power significantly superior to the clinicopathologic factors alone [c-indices: 0.764 vs. 0.750, P = 0.024 (ABCSG-6) and 0.726 vs. 0.701, P = 0.003 (ABCSG-8)]. EPclin had c-indices of 0.788 and 0.732 and resulted in 10-year distant recurrence rates of 4% and 4% in EPclin low-risk and 28% and 22% in EPclin high-risk patients in ABCSG-6 (P < 0.001) and ABCSG-8 (P < 0.001), respectively.
The multigene EP risk score provided additional prognostic information to the risk of distant recurrence of breast cancer patients, independent from clinicopathologic parameters. The EPclin score outperformed all conventional clinicopathologic risk factors.
根据现行指南，预测乳腺癌患者治疗结局的分子检测可用于辅助在考虑常规标志物后制定治疗决策。我们开发并验证了一种基因表达特征，用于预测接受辅助内分泌治疗的雌激素受体（ER）阳性、HER2 阴性乳腺癌患者发生远处复发的可能性。
使用定量逆转录聚合酶链反应（qRT-PCR）评估福尔马林固定、石蜡包埋的肿瘤组织中的 RNA 水平，以计算由 8 个癌症相关基因和 3 个参考基因组成的风险评分（Endopredict，EP）。EP 与淋巴结状态和肿瘤大小相结合，形成一个综合风险评分 EPclin。两个预先指定的风险评分均包含确定每个患者风险组（低危和高危）的截值，并在两项大型随机 III 期临床试验[奥地利乳腺癌和结直肠癌研究组（ABCSG）-6：n=378，ABCSG-8：n=1324]中独立验证。
在两个验证队列中，连续 EP 是多变量分析中远处复发的独立预测因子（ABCSG-6：P=0.010，ABCSG-8：P<0.001）。将 Adjuvant!Online、定量 ER、Ki67 和治疗与 EP 相结合，产生的预后能力明显优于单独的临床病理因素[C 指数：0.764 与 0.750，P=0.024（ABCSG-6）和 0.726 与 0.701，P=0.003（ABCSG-8）]。EPclin 的 C 指数分别为 0.788 和 0.732，在 ABCSG-6 中，EPclin 低危组和高危组的 10 年远处复发率分别为 4%和 4%，而 EPclin 低危组和高危组的 10 年远处复发率分别为 28%和 22%（P<0.001），在 ABCSG-8 中，分别为 28%和 22%（P<0.001）。
多基因 EP 风险评分提供了乳腺癌患者远处复发风险的额外预后信息，独立于临床病理参数。EPclin 评分优于所有传统临床病理危险因素。
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