Endothelial Cell pY397-FAK Expression Predicts the Risk of Breast Cancer Recurrences after Radiotherapy in the SweBCG91-RT Cohort.

In this study, we tested the interaction between endothelial cell (EC) expression of phospho-Tyr397-FAK (pY397-FAK) and adjuvant-RT on clinical outcomes after breast-conserving surgery (BCS) within a randomized study.

在这项研究中，我们在一项随机研究中测试了内皮细胞（EC）表达磷酸化Tyr397-FAK（pY397-FAK）与辅助放射治疗（RT）在乳腺保留手术（BCS）后的临床结果之间的相互作用。

Preclinical data suggest an enhanced effect of RT on low EC_pY397-FAK expression.

临床前数据表明，低EC_pY397-FAK表达对放射治疗（RT）的增强效应有影响。

experimental_design

We analyzed tissue microarrays from the Swedish Breast Cancer Group 91 Radiotherapy (stage I-II, lymph node-negative) breast cancer cohort, consisting of 1,178 patients randomly assigned to receive either BCS alone or BCS plus adjuvant-RT.

我们分析了来自瑞典乳腺癌放射治疗组91（I-II期，淋巴结阴性）乳腺癌队列的组织微阵列，该队列包括1,178名随机分配接受单纯乳腺保守治疗（BCS）或BCS加辅助放射治疗（adjuvant-RT）的患者。

Tissue microarray sections were immunostained for pY397-FAK, CD31, α-smooth muscle actin, and pan-cytokeratin.

组织微阵列切片进行了pY397-FAK、CD31、α-平滑肌肌动蛋白和泛细胞角蛋白的免疫染色。

HALO analysis scored mean pY397-FAK intensity in CD31+ ECs, pan-cytokeratin-positive tumor epithelial cells, and α-smooth muscle actin + mural/stromal cells per core.

HALO分析计算了每芯CD31+内皮细胞、泛细胞角蛋白阳性肿瘤上皮细胞和α-平滑肌肌动蛋白+壁/基质细胞中pY397-FAK平均强度。

For 822 patients, multivariable Cox regression analysis was performed for the primary and secondary 5-year endpoints, locoregional recurrence and all recurrence, respectively, as dependent variables and RT and EC_pY397-FAK as independent variables.

对822名患者进行了多变量Cox回归分析，以5年主要终点和次要终点（局部区域复发和所有复发）为因变量，放射治疗（RT）和EC_pY397-FAK表达为自变量。

Results

EC_pY397-FAK expression was not predictive for the primary endpoint locoregional recurrence (P = 0.098), but the direction of the RT effect was in line with preclinical findings.

EC_pY397-FAK表达对于主要终点局部区域复发的预测并不显著（P = 0.098），但放射治疗的效果方向与临床前研究发现一致。

For the secondary endpoint all recurrence, there was a significant interaction (P = 0.026) between EC_pY397-FAK and RT.

次要终点为所有复发时，EC_pY397-FAK和放疗（RT）之间存在显著的相互作用（P = 0.026）。

Without RT, higher EC_pY397-FAK expression resulted in a lower risk for all recurrence (HR = 0.74 per SD; 95% confidence interval= 0.57-0.96; P = 0.026).

没有放疗的情况下，更高的EC_pY397-FAK表达与所有复发的较低风险相关（每标准差风险比HR = 0.74；95%置信区间 = 0.57-0.96；P = 0.026）。

Conclusions

Within the first 5 years following BCS, patients with low EC_pY397-FAK expression derive greater benefit from RT than patients with high EC_pY397-FAK expression.

在BCS后的前5年内，低EC_pY397-FAK表达的患者从放疗中获得的益处大于高EC_pY397-FAK表达的患者。

However, without RT, low EC_pY397-FAK expression is associated with a higher risk of recurrence.

然而，没有放疗的情况下，低EC_pY397-FAK表达与复发风险较高相关。