Department of Surgery, Institut Curie, Paris, France.
PLoS One. 2011;6(5):e20297. doi: 10.1371/journal.pone.0020297. Epub 2011 May 31.
Several authors have underscored a strong relation between the molecular subtypes and the axillary status of breast cancer patients. The aim of our work was to decipher the interaction between this classification and the probability of a positive sentinel node biopsy.
Our dataset consisted of a total number of 2654 early-stage breast cancer patients. Patients treated at first by conservative breast surgery plus sentinel node biopsies were selected. A multivariate logistic regression model was trained and validated. Interaction covariate between ER and HER2 markers was a forced input of this model. The performance of the multivariate model in the training and the two validation sets was analyzed in terms of discrimination and calibration. Probability of axillary metastasis was detailed for each molecular subtype.
The interaction covariate between ER and HER2 status was a stronger predictor (p = 0.0031) of positive sentinel node biopsy than the ER status by itself (p = 0.016). A multivariate model to determine the probability of sentinel node positivity was defined with the following variables; tumour size, lympho-vascular invasion, molecular subtypes and age at diagnosis. This model showed similar results in terms of discrimination (AUC = 0.72/0.73/0.72) and calibration (HL p = 0.28/0.05/0.11) in the training and validation sets. The interaction between molecular subtypes, tumour size and sentinel nodes status was approximated.
We showed that biologically-driven analyses are able to build new models with higher performance in terms of breast cancer axillary status prediction. The molecular subtype classification strongly interacts with the axillary and distant metastasis process.
多位作者强调了乳腺癌患者的分子亚型与腋窝状态之间存在很强的关系。我们的研究目的是解读这种分类与前哨淋巴结活检阳性概率之间的相互作用。
我们的数据集包含 2654 名早期乳腺癌患者。选择了首次接受保乳手术加前哨淋巴结活检的患者。建立并验证了一个多变量逻辑回归模型。该模型的输入变量中强制纳入了 ER 和 HER2 标志物之间的交互协变量。分析了多变量模型在训练集和两个验证集中的区分度和校准度。为每个分子亚型详细描述了腋窝转移的概率。
ER 和 HER2 状态之间的交互协变量是预测前哨淋巴结活检阳性的更强预测因子(p=0.0031),比 ER 状态本身(p=0.016)更强。定义了一个用于确定前哨淋巴结阳性概率的多变量模型,纳入的变量包括肿瘤大小、淋巴血管侵犯、分子亚型和诊断时的年龄。该模型在训练集和验证集的区分度(AUC=0.72/0.73/0.72)和校准度(HL p=0.28/0.05/0.11)方面表现相似。近似模拟了分子亚型、肿瘤大小和前哨淋巴结状态之间的相互作用。
我们表明,基于生物学的分析能够构建新的模型,在预测乳腺癌腋窝状态方面具有更高的性能。分子亚型分类与腋窝和远处转移过程强烈相互作用。