PTHrP, A Biomarker for CNS Metastasis in Triple-Negative Breast Cancer and Selection for Adjuvant Chemotherapy in Node-Negative Disease
PTHrP, A Biomarker for CNS Metastasis in Triple-Negative Breast Cancer and Selection for Adjuvant Chemotherapy in Node-Negative Disease
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DOI：
10.1093/jncics/pkz063
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发表时间：
2020-02-01
影响因子：
4.4
通讯作者：
Sabri, Siham
中科院分区：
文献类型：
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作者：
Assaker, Gloria;Camirand, Anne;Sabri, Siham
背景：三阴性乳腺癌（TNBC）的特点是预后差，缺乏靶向治疗和生物标志物来指导辅助化疗的决定。甲状旁腺激素相关蛋白（PTHrP）在乳腺癌中经常过表达，并参与增殖和转移，这是淋巴结阴性乳腺癌预后不良的两个标志。我们研究了PTHrP在TNBC中器官特异性转移和淋巴结状态方面的预后价值。方法：在314例新诊断为TNBC的患者中，我们使用免疫组化技术在临床注释的组织芯片中评估PTHrP的表达，然后使用Kaplan-Meier和Cox回归分析其与进展和生存的相关性。通过Bioconductor进行癌症基因组图谱（TCGA）验证分析。所有统计检验均为双侧检验。结果：在单因素分析中，PTHrP过表达（290例可评分病例中有160例，55.2%）与我们队列中总生存率（OS）降低（P = 0.0055）和癌症基因组图谱（P = 0.0018）以及中枢神经系统（CNS）无进展生存率降低（P = 0.0029）具有统计学意义。在多变量分析中，PTHrP是TNBC患者cns -无进展生存的独立预后因素（风险比[HR] = 5.014, 95%可信区间[CI] = 1.421 ~ 17.692, P = 0.0122），以及淋巴结阴性TNBC患者选择性OS的独立预后因素（风险比[HR] = 2.423, 95% CI = 1.129 ~ 5.197, P = 0.0231）。值得注意的是，对于未接受辅助化疗的低临床风险淋巴结阴性患者的OS， PTHrP成为唯一具有统计学意义的预后因素（HR = 2.576, 95% CI = 1.019 ~ 6.513, P = 0.0456）。结论：PTHrP是影响低临床风险淋巴结阴性TNBC中枢神经系统转移和辅助化疗选择的一个新的独立预后因素。其预测价值需要在临床试验中进行前瞻性评估。
Background: Triple-negative breast cancer (TNBC) is characterized by poor prognosis and lack of targeted therapies and biomarkers to guide decisions on adjuvant chemotherapy. Parathyroid hormone-related protein (PTHrP) is frequently overexpressed in breast cancer and involved in proliferation and metastasis, two hallmarks of poor prognosis for node-negative breast cancer. We investigated the prognostic value of PTHrP with respect to organ-specific metastasis and nodal status in TNBC.Methods: We assessed PTHrP expression using immunohistochemistry in a clinically annotated tissue microarray for a population-based study of 314 patients newly diagnosed with TNBC, then analyzed its correlation to progression and survival using Kaplan-Meier and Cox regression analyses. The Cancer Genome Atlas (TCGA) validation analysis was performed through Bioconductor. All statistical tests were two-sided.Results: PTHrP overexpression (160 of 290 scorable cases, 55.2%) was statistically significantly associated in univariate analysis with decreased overall survival (OS) in our cohort (P = .0055) and The Cancer Genome Atlas (P = .0018) and decreased central nervous system (CNS)-progression-free survival (P = .0029). In multivariate analysis, PTHrP was a statistically significant independent prognostic factor for CNS-progression-free survival in TNBC (hazard ratio [HR] = 5.014, 95% confidence interval [CI] = 1.421 to 17.692, P = .0122) and for OS selectively in node-negative TNBC (HR= 2.423, 95% CI = 1.129 to 5.197, P = .0231). Strikingly, PTHrP emerged as the only statistically significant prognostic factor (HR = 2.576, 95% CI = 1.019 to 6.513, P = .0456) for OS of low-clinical risk node-negative patients who did not receive adjuvant chemotherapy.Conclusions: PTHrP is a novel independent prognostic factor for CNS metastasis and adjuvant chemotherapy selection of low-clinical risk node-negative TNBC. Its predictive value needs to be prospectively assessed in clinical trials.