Postdiagnosis circulating osteoprotegerin and TRAIL concentrations and survival and recurrence after a breast cancer diagnosis: results from the MARIE patient cohort.

Charlotte Le Cornet, Audrey Y Jung, Theron S Johnson, Sabine Behrens, Nadia Obi, Heiko Becher, Jenny Chang-Claude, Renée T Fortner
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Abstract

Background: Experimental studies suggest a role for osteoprotegerin (OPG) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in mammary tumor development and progression. These biomarkers have been minimally investigated with respect to outcomes in breast cancer patients.

Methods: OPG and TRAIL were evaluated in blood samples collected from 2459 breast cancer patients enrolled in the MARIE study, a prospective population-based patient cohort, at median of 129 days after diagnosis. Participants were between ages 50 and 74 at diagnosis and recruited from 2002 to 2005 in two regions of Germany. Follow-up for recurrence and mortality was conducted through June 2015. Delayed-entry Cox proportional hazards regression was used to assess associations between OPG and TRAIL with all-cause and breast cancer-specific mortality, and recurrence, both overall and by tumor hormone receptor status.

Results: Median follow-up time was 11.7 years, with 485 deaths reported (277 breast cancer-specific). Higher OPG concentrations were associated with a higher risk of all-cause mortality (hazard ratio for 1-unit log2-transformed concentration (HRlog2) = 1.24 (95% confidence interval 1.03-1.49). Associations were observed in women diagnosed with ER-PR- tumors or discordant hormone receptor status (ER-PR-, HRlog2 = 1.93 (1.20-3.10); discordant ERPR, 1.70 (1.03-2.81)), but not for women with ER + PR + tumors (HRlog2 = 1.06 (0.83-1.35)). OPG was associated with a higher risk of recurrence among women with ER-PR- disease (HRlog2 = 2.18 (1.39-3.40)). We observed no associations between OPG and breast cancer-specific survival, or for TRAIL and any outcome.

Conclusions: Higher circulating OPG may be a biomarker of a higher risk of poor outcome among women diagnosed with ER- breast cancer. Further mechanistic studies are warranted.

Abstract Image

Abstract Image

诊断后循环骨保护素和TRAIL浓度与乳腺癌诊断后生存和复发:来自MARIE患者队列的结果
背景:实验研究表明,骨保护素(OPG)和肿瘤坏死因子相关凋亡诱导配体(TRAIL)在乳腺肿瘤的发生和发展中起着重要作用。这些生物标志物在乳腺癌患者预后方面的研究很少。方法:在诊断后中位时间129天,对入选MARIE研究(一项前瞻性人群为基础的患者队列)的2459例乳腺癌患者的血液样本进行OPG和TRAIL评估。参与者在诊断时年龄在50至74岁之间,于2002年至2005年在德国两个地区招募。随访随访至2015年6月。使用延迟进入Cox比例风险回归来评估OPG和TRAIL与全因和乳腺癌特异性死亡率以及总体和肿瘤激素受体状态的复发率之间的关系。结果:中位随访时间为11.7年,报告485例死亡(277例乳腺癌特异性死亡)。较高的OPG浓度与较高的全因死亡风险相关(1单位log2转化浓度的风险比(HRlog2) = 1.24(95%置信区间1.03-1.49)。在诊断为ER-PR-肿瘤或激素受体状态不一致的女性中观察到相关(ER-PR-, HRlog2 = 1.93 (1.20-3.10);不一致的ERPR为1.70(1.03-2.81)),但ER + PR +肿瘤女性的HRlog2 = 1.06(0.83-1.35)。在ER-PR-疾病的女性中,OPG与较高的复发风险相关(HRlog2 = 2.18(1.39-3.40))。我们没有观察到OPG和乳腺癌特异性生存之间的关联,也没有观察到TRAIL和任何结果之间的关联。结论:较高的循环OPG可能是诊断为ER-乳腺癌的女性预后不良风险较高的生物标志物。进一步的机理研究是有必要的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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