Department of Pathology, Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA.
J Natl Cancer Inst. 2013 Jul 17;105(14):1036-42. doi: 10.1093/jnci/djt146. Epub 2013 Jun 28.
Biomarkers to optimize extended adjuvant endocrine therapy for women with estrogen receptor (ER)-positive breast cancer are limited. The HOXB13/IL17BR (H/I) biomarker predicts recurrence risk in ER-positive, lymph node-negative breast cancer patients. H/I was evaluated in MA.17 trial for prognostic performance for late recurrence and treatment benefit from extended adjuvant letrozole.
A prospective-retrospective, nested case-control design of 83 recurrences matched to 166 nonrecurrences from letrozole- and placebo-treated patients within MA.17 was conducted. Expression of H/I within primary tumors was determined by reverse-transcription polymerase chain reaction with a prespecified cutpoint. The predictive ability of H/I for ascertaining benefit from letrozole was determined using multivariable conditional logistic regression including standard clinicopathological factors as covariates. All statistical tests were two-sided.
High H/I was statistically significantly associated with a decrease in late recurrence in patients receiving extended letrozole therapy (odds ratio [OR] = 0.35; 95% confidence interval [CI] = 0.16 to 0.75; P = .007). In an adjusted model with standard clinicopathological factors, high H/I remained statistically significantly associated with patient benefit from letrozole (OR = 0.33; 95% CI = 0.15 to 0.73; P = .006). Reduction in the absolute risk of recurrence at 5 years was 16.5% for patients with high H/I (P = .007). The interaction between H/I and letrozole treatment was statistically significant (P = .03).
In the absence of extended letrozole therapy, high H/I identifies a subgroup of ER-positive patients disease-free after 5 years of tamoxifen who are at risk for late recurrence. When extended endocrine therapy with letrozole is prescribed, high H/I predicts benefit from therapy and a decreased probability of late disease recurrence.
用于优化雌激素受体（ER）阳性乳腺癌患者的延长辅助内分泌治疗的生物标志物有限。HOXB13/IL17BR（H/I）生物标志物可预测 ER 阳性、淋巴结阴性乳腺癌患者的复发风险。在 MA.17 试验中，评估了 H/I 对晚期复发的预后表现和延长辅助来曲唑治疗的获益。
采用前瞻性-回顾性、巢式病例对照设计，对 MA.17 中接受来曲唑和安慰剂治疗的患者中 83 例复发患者与 166 例无复发患者进行了配对。通过逆转录聚合酶链反应测定原发肿瘤中 H/I 的表达，使用多变量条件逻辑回归，将标准临床病理因素作为协变量，确定 H/I 对来曲唑获益的预测能力。所有统计检验均为双侧。
高 H/I 与接受延长来曲唑治疗的患者晚期复发风险降低显著相关（比值比[OR] = 0.35；95%置信区间[CI] = 0.16 至 0.75；P =.007）。在包含标准临床病理因素的调整模型中，高 H/I 与来曲唑治疗的患者获益仍显著相关（OR = 0.33；95%CI = 0.15 至 0.73；P =.006）。高 H/I 患者的 5 年复发绝对风险降低 16.5%（P =.007）。H/I 和来曲唑治疗之间的交互作用具有统计学意义（P =.03）。
在没有延长来曲唑治疗的情况下，高 H/I 可识别出在接受他莫昔芬 5 年治疗后无疾病的 ER 阳性患者亚组，这些患者有发生晚期复发的风险。当给予来曲唑延长内分泌治疗时，高 H/I 可预测治疗获益和晚期疾病复发的可能性降低。
