The Magnitude of Androgen Receptor Positivity in Breast Cancer Is Critical for Reliable Prediction of Disease Outcome
The Magnitude of Androgen Receptor Positivity in Breast Cancer Is Critical for Reliable Prediction of Disease Outcome
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DOI：
10.1158/1078-0432.ccr-17-1199
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发表时间：
2018-05-15
影响因子：
11.5
通讯作者：
Tilley, Wayne D.
中科院分区：
文献类型：
--
作者：
Ricciardelli, Carmela;Bianco-Miotto, Tina;Tilley, Wayne D.
目的：关于雄激素受体（AR）作为乳腺癌的预后标志物缺乏共识，本研究的目的是全面回顾AR检测的文献，并确定AR作为乳腺癌生存率的独立预测因子的最佳标准。验证队列，n = 418;分别为77%和79%雌激素受体α（ER α）阳性]。最佳AR切割点确定ROC分析在训练队列和适用于两个cohols.Results：AR是一个独立的乳腺癌预后标志物在22 46（48%）以前的研究进行多变量分析。大多数研究使用1%或10%核阳性的临界点。在此，1%或10%的临界点均不是稳健的预后。ROC分析显示，较高的AR临界点（78%阳性）为预测训练（HR，0.41; P 0.015）和验证（HR，0.50; P = 0.014）队列中的乳腺癌生存率提供了最佳的灵敏度和特异性。十倍交叉验证证实了该AR临界点的稳健性。两个队列中ER a阳性肿瘤且AR阳性>= 78%的患者生存率最高（P < 0.0001）。在联合ER α阳性病例中，AR水平相当或更高（AR：ER α阳性率>0.87）的患者结局最好（P < 0.0001）。结论：本研究确定了可靠预测乳腺癌生存率的最佳AR临界点。在前瞻性队列中测试这一临界点对于将AR作为乳腺癌临床管理中的预后因素是有必要的。(C)2018年AACR。
Purpose: Consensus is lacking regarding the androgen receptor (AR) as a prognostic marker in breast cancer.The objectives of this study were to comprehensively review the literature on AR prognostication and determine optimal criteria for AR as an independent predictor of breast cancer survival.Experimental Design: AR positivity was assessed by immunostaining in two clinically validated primary breast cancer cohorts [training cohort, n = 219; validation cohort, n = 418; 77% and 79% estrogen receptor alpha (ER alpha) positive, respectively]. The optimal AR cut point was determined by ROC analysis in the training cohort and applied to both cohorts.Results: AR was an independent prognostic marker of breast cancer outcome in 22 of 46 (48%) previous studies that performed multivariate analyses. Most studies used cut-points of 1% or 10% nuclear positivity. Herein, neither 1% nor 10% cut-points were robustly prognostic. ROC analysis revealed that a higher AR cut point (78% positivity) provided optimal sensitivity and specificity to predict breast cancer survival in the training (HR, 0.41; P 0.015) and validation (HR, 0.50; P = 0.014) cohorts,Tenfold cross-validation confirmed the robustness of this AR cut-point. Patients with ERa-positive tumors and AR positivity >= 78% had the best survival in both cohorts (P < 0.0001). Among the combined ER alpha-positive cases, those with comparable or higher levels of AR (AR:ER alpha positivity ratio >0.87) had the best outcomes (P < 0.0001).Conclusions: This study defines an optimal AR cut-point to reliably predict breast cancer survival. Testing this cut-point in prospective cohorts is warranted for implementation of AR as a prognostic factor in the clinical management of breast cancer. (C) 2018 AACR.