Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain,
Clin Transl Oncol. 2014 Apr;16(4):386-94. doi: 10.1007/s12094-013-1088-z. Epub 2013 Aug 2.
Breast cancer subtypes can be identified by genomic testing or pathology-based approximations. However, these classifications are not equivalent and the clinical relevance of both classifications needs to be fully explored.
Ninety-four patients were randomized to neoadjuvant single agent doxorubicin or docetaxel. Tumor subtype was assessed by pathology-based classification and by gene expression using the PAM50 plus the claudin-low predictor (CLP). Kappa Cohen's coefficient (κ) was used to test the agreement between methods. Multivariate Cox proportional hazards analyses were used to determine the significance of each methodology in the prediction of prognosis. Likelihood ratio statistics of both classifications were evaluated.
The agreement between pathology-based classification and PAM50 was moderate [κ = 0.551, 95 % confidence interval (95 % CI) 0.467-0.641]. Tumor subtype assessed by both classifications were prognostic for overall survival (OS) and relapse-free survival (P < 0.05). However, PAM50 + CLP provided more prognostic information, in terms of OS, than the pathology-based classification (P < 0.05). Patients with triple negative tumors as well as basal-like tumors had worse OS when first treated with doxorubicin (HR = 5.98, 95 % CI 1.25-28.67, and HR = 5.02, 95 % CI 0.96-26.38, respectively). However, claudin-low tumors did not show significant differences in OS according to neoadjuvant treatment branch. Indeed, we found that claudin-low tumors treated with pre-operative doxorubicin had significantly better OS than basal-like tumors treated with neoadjuvant doxorubicin (adjusted HR = 0.16, 95 % CI 0.04-0.69, P = 0.014).
The assignment of tumor subtype can differ depending on the methodology, which might have implications on patient's management and therapy selection.
乳腺癌亚型可通过基因组检测或基于病理的近似方法来识别。然而，这些分类并不等同，需要充分探索这两种分类的临床相关性。
94 例患者被随机分配接受新辅助单药多柔比星或多西他赛治疗。通过基于病理的分类和使用 PAM50 加 Claudin-low 预测因子（CLP）的基因表达来评估肿瘤亚型。采用 Kappa Cohen 系数（κ）检验方法间的一致性。采用多变量 Cox 比例风险分析确定每种方法在预测预后中的意义。评估两种分类的似然比统计数据。
基于病理的分类与 PAM50 的一致性为中度[κ=0.551，95%置信区间（95%CI）0.467-0.641]。两种分类评估的肿瘤亚型均与总生存（OS）和无复发生存（RFS）相关（P<0.05）。然而，与基于病理的分类相比，PAM50+CLP 提供了更多的预后信息，尤其是在 OS 方面（P<0.05）。首先接受多柔比星治疗的三阴性肿瘤和基底样肿瘤患者的 OS 较差（HR=5.98，95%CI 1.25-28.67，和 HR=5.02，95%CI 0.96-26.38）。然而，Claudin-low 肿瘤在新辅助治疗分支中，OS 无显著差异。事实上，我们发现接受术前多柔比星治疗的 Claudin-low 肿瘤的 OS 明显优于接受新辅助多柔比星治疗的基底样肿瘤（调整后的 HR=0.16，95%CI 0.04-0.69，P=0.014）。
肿瘤亚型的分配可能因方法而异，这可能对患者的管理和治疗选择产生影响。
