Exploring the two-gene ratio in breast cancer -: independent roles for HOXB13 and IL17BR in prediction of clinical outcome
Exploring the two-gene ratio in breast cancer -: independent roles for HOXB13 and IL17BR in prediction of clinical outcome
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DOI：
10.1007/s10549-007-9541-8
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发表时间：
2008-01-01
影响因子：
3.8
通讯作者：
Stal, Olle
中科院分区：
文献类型：
--
作者：
Jerevall, Piiha-Lotta;Brommesson, Sara;Stal, Olle
HOX-B13：IL 17 BR双基因表达比率已被提议用于预测他莫昔芬治疗的乳腺癌患者的结果。我们的目的是检查这个比值是否可以预测绝经后患者接受他莫昔芬治疗5年与2年的获益。另一个目的是调查任何预后的影响比率在系统未经治疗的绝经前患者。基于目前对HOXB 13和IL 17 BR的了解，我们假设这些基因可能具有个体预后或预测能力。患者和方法通过实时PCR定量来自264名随机绝经后患者和93名全身未经治疗的绝经前患者的肿瘤中HOXB 13和IL 17 BR的表达。IL 17 BR比率与侵袭性肿瘤特征相关，单独的低水平IL 17 BR也是如此。该比值和HOXB 13单独预测内分泌治疗后的无复发生存率，雌激素受体阳性患者延长治疗的益处与低比值（复发率比值：RR = 0.39; P = 0.030）或HOXB 13低表达（RR = 0.37; P = 0.015）相关。高比率或高HOXB 13亚组的无复发生存率无差异。多因素分析显示HOXB 13和HOXB 13：IL 17 BR的预测价值有统计学意义。在全身未经治疗的队列中，只有IL 17 BR表现出独立的预后significant.Conclusion，我们得出结论，该比率或HOXB 13单独可以预测内分泌治疗的好处，高比率或高表达使患者不太可能响应。我们还表明，IL 17 BR可能是乳腺癌的一个独立的预后因素。
Background The two-gene expression ratio HOX-B13: IL17BR has been proposed to predict the outcome of tamoxifen-treated breast cancer patients. We intended to examine whether this ratio can predict the benefit of 5 years vs. 2 years of tamoxifen treatment of postmenopausal patients. A further objective was to investigate any prognostic effects of the ratio in systematically untreated premenopausal patients. Based on the current knowledge of HOXB13 and IL17BR, we hypothesized that these genes may have individual prognostic or predictive power.Patients and methods Expression of HOXB13 and IL17BR were quantified by real-time PCR in tumors from 264 randomized postmenopausal patients and 93 systemically untreated premenopausal patients.Results A high HOXB13: IL17BR ratio was associated with aggressive tumor characteristics, as were low levels of IL17BR alone. The ratio and HOXB13 alone predicted recurrence-free survival after endocrine treatment, with a benefit of prolonged treatment in estrogen receptor-positive patients correlated to a low ratio (recurrence rate ratio: RR = 0.39; P = 0.030), or low expression of HOXB13 (RR = 0.37; P = 0.015). No difference in recurrence-free survival was seen for the high ratio or high HOXB13 subgroups. The predictive value of HOXB13 and HOXB13: IL17BR was significant in multivariate analysis. In the systemically untreated cohort, only IL17BR showed independent prognostic significance.Conclusion We conclude that the ratio or HOXB13 alone can predict the benefit of endocrine therapy, with a high ratio or a high expression rendering patients less likely to respond. We have also shown that IL17BR might be an independent prognostic factor in breast cancer.