Immune and Growth Factor Signaling Pathways Are Associated with Pathologic Complete Response to an Anti-Type I Insulin-like Growth Factor Receptor Regimen in Patients with Breast Cancer.

The primary endpoint of this trial is pathologic complete response (pCR).

该试验的主要终点是病理完全缓解(pCR)。

experimental_design

One hundred six patients treated with PGM and 119 contemporary controls were evaluated using laser capture microdissection and reverse-phase protein array to evaluate 32 prespecified potential predictive biomarkers in the IGF-1R pathway and 109 additional exploratory endpoints.

使用激光捕获显微切割和反相蛋白质阵列评估了106名接受PGM治疗的患者和119名当代对照组，以评估IGF-1R通路中32个预先设定的潜在预测生物标志物和109个额外的探索性终点。

Results

Total levels of IGF-1R were poorly correlated with phosphorylated IGF-1R/insulin receptor (IR).

IGF-1R的总水平与磷酸化IGF-1R/胰岛素受体（IR）的相关性较差。

Higher levels of phosphorylated IGF-1R/IR were associated with an increased likelihood of obtaining pCR, especially in the hormone receptor (HR)-positive subgroup.

磷酸化IGF-1R/IR水平较高与获得病理完全缓解(pCR)的可能性增加有关，特别是在激素受体(HR)阳性亚组中。

Markers of immune response also showed an association with pCR but differed between HR+ and HR- subgroups.

免疫反应标志物也显示出与pCR的关联，但在HR+和HR-亚组之间存在差异。

In HR- tumors, phospho-STAT1 Y701 and low levels of phospho-p27 associated with pCR.

在HR-肿瘤中，磷酸化STAT1 Y701和磷酸化p27低水平与病理完全缓解(pCR)相关。

These relationships were not observed in patients treated with control chemotherapy.

在接受对照化疗的患者中，未观察到这些关系。

Conclusions

Activation status of IGF-1R/IR associated with increased pCR to PGM in HR+ breast cancers.

IGF-1R/IR的激活状态与激素受体阳性（HR+）乳腺癌中对化疗药物PGM的病理完全缓解（pCR）增加相关。

Immune activation markers were also associated with response in HR+ and HR- subgroups.

免疫激活标志物也与激素受体阳性（HR+）和激素受体阴性（HR-）亚组的治疗反应相关。

Thus, IGF-1R may directly regulate tumor biology and associate with immune response to therapy.

因此，IGF-1R可能直接调控肿瘤生物学并影响对治疗的免疫反应。