将放射敏感性分子特征纳入乳腺癌局部复发风险评估
Integration of a Radiosensitivity Molecular Signature Into the Assessment of Local Recurrence Risk in Breast Cancer.
作者信息
Torres-Roca Javier F, Fulp William J, Caudell Jimmy J, Servant Nicolas, Bollet Marc A, van de Vijver Marc, Naghavi Arash O, Harris Eleanor E, Eschrich Steven A
机构信息
Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida; Department of Chemical Biology and Molecular Medicine, Moffitt Cancer Center, Tampa, Florida.
Department of Bioinformatics, Moffitt Cancer Center, Tampa, Florida; Department of Biostatistics, Moffitt Cancer Center, Tampa, Florida.
出版信息
Int J Radiat Oncol Biol Phys. 2015 Nov 1;93(3):631-8. doi: 10.1016/j.ijrobp.2015.06.021. Epub 2015 Jun 25.
PURPOSE
Recently, we developed radiosensitivity (RSI), a clinically validated molecular signature that estimates tumor radiosensitivity. In the present study, we tested whether integrating RSI with the molecular subtype refines the classification of local recurrence (LR) risk in breast cancer.
METHODS AND MATERIALS
RSI and molecular subtype were evaluated in 343 patients treated with breast-conserving therapy that included whole-breast radiation therapy with or without a tumor bed boost (dose range 45-72 Gy). The follow-up period for patients without recurrence was 10 years. The clinical endpoint was LR-free survival.
RESULTS
Although RSI did not uniformly predict for LR across the entire cohort, combining RSI and the molecular subtype identified a subpopulation with an increased risk of LR: triple negative (TN) and radioresistant (reference TN-radioresistant, hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.15-0.92, P=.02). TN patients who were RSI-sensitive/intermediate had LR rates similar to those of luminal (LUM) patients (HR 0.86, 95% CI 0.47-1.57, P=.63). On multivariate analysis, combined RSI and molecular subtype (P=.004) and age (P=.001) were the most significant predictors of LR. In contrast, integrating RSI into the LUM subtype did not identify additional risk groups. We hypothesized that radiation dose escalation was affecting radioresistance in the LUM subtype and serving as a confounder. An increased radiation dose decreased LR only in the luminal-resistant (LUM-R) subset (HR 0.23, 95% CI 0.05-0.98, P=.03). On multivariate analysis, the radiation dose was an independent variable only in the LUMA/B-RR subset (HR 0.025, 95% CI 0.001-0.946, P=.046), along with age (P=.008), T stage (P=.004), and chemotherapy (P=.008).
CONCLUSIONS
The combined molecular subtype-RSI identified a novel molecular subpopulation (TN and radioresistant) with an increased risk of LR after breast-conserving therapy. We propose that the combination of RSI and molecular subtype could be useful in guiding radiation therapy-based decisions in breast cancer.
目的
最近，我们开发了放射敏感性指数（RSI），这是一种经过临床验证的分子标志物，用于评估肿瘤放射敏感性。在本研究中，我们测试了将RSI与分子亚型相结合是否能优化乳腺癌局部复发（LR）风险的分类。
方法和材料
对343例接受保乳治疗的患者进行了RSI和分子亚型评估，保乳治疗包括全乳放疗，有或没有瘤床加量（剂量范围45-72 Gy）。无复发患者的随访期为10年。临床终点为无局部复发生存期。
结果
尽管RSI并不能在整个队列中一致地预测LR，但将RSI和分子亚型相结合可识别出LR风险增加的亚组：三阴性（TN）且放射抵抗（参考TN-放射抵抗，风险比[HR] 0.37，95%置信区间[CI] 0.15-0.92，P = 0.02）。RSI敏感/中等的TN患者的LR率与管腔型（LUM）患者相似（HR = 0.86，95% CI 0.47-1.57，P = 0.63）。多因素分析显示，RSI与分子亚型的联合（P = 0.004）和年龄（P = 0.001）是LR的最显著预测因素。相比之下，将RSI纳入LUM亚型并未识别出额外的风险组。我们推测，放疗剂量增加影响了LUM亚型的放射抵抗，并成为一个混杂因素。放疗剂量增加仅在管腔型抵抗（LUM-R）亚组中降低了LR（HR = 0.23，95% CI 0.05-0.98，P = 0.03）。多因素分析显示，放疗剂量仅在LUM A/B-RR亚组中是一个独立变量（HR = 0.025，95% CI 0.001-0.946，P = 0.046），同时还有年龄（P = 0.008）、T分期（P = 0.004）和化疗（P = 0.008）。
结论
分子亚型与RSI的联合识别出一个新的分子亚组（TN且放射抵抗），其在保乳治疗后LR风险增加。我们建议，RSI与分子亚型的联合可能有助于指导乳腺癌基于放疗的决策。
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