Dynamic biomarkers that permit the real-time monitoring of the tumor microenvironment response to therapy are an unmet need in breast cancer. Breast magnetic resonance imaging (MRI) has demonstrated value as a predictor of pathologic complete response and may reflect immune cell changes in the tumor microenvironment. The purpose of this pilot study was to investigate the value of breast MRI features as early markers of treatment-induced immune response. Fourteen patients with early HER2+ breast cancer were enrolled in a window-of-opportunity study where a single dose of trastuzumab was administered and both tissue and MRIs were obtained at the pre- and post-treatment stages. Functional diffusion-weighted and dynamic contrast-enhanced MRI tumor measures were compared with tumor-infiltrating lymphocytes (TILs) and RNA immune signature scores. Both the pre-treatment apparent diffusion coefficient (ADC) and the change in peak percent enhancement (DPE) were associated with increased tumor-infiltrating lymphocytes with trastuzumab therapy (r = −0.67 and -0.69,p< 0.01 andp< 0.01, respectively). Low pre-treatment ADC and a greater decrease in PE in response to treatment were also associated with immune-activated tumor microenvironments as defined by RNA immune signatures. Breast MRI features hold promise as biomarkers of early immune response to treatment in HER2+ breast cancer.
能够实时监测肿瘤微环境对治疗反应的动态生物标志物，是乳腺癌领域尚未满足的需求。乳腺磁共振成像（MRI）已被证明可作为病理完全缓解的预测指标，并可能反映肿瘤微环境中免疫细胞的变化。本项探索性研究旨在探讨乳腺MRI特征作为治疗诱导免疫反应早期标志物的价值。研究纳入了14例早期HER2阳性乳腺癌患者，进行了一项治疗窗口期研究，患者接受单剂量曲妥珠单抗治疗，并在治疗前后分别获取组织样本和MRI图像。研究将功能性扩散加权成像和动态对比增强MRI的肿瘤测量指标与肿瘤浸润淋巴细胞（TILs）及RNA免疫特征评分进行比较。结果显示，治疗前的表观扩散系数（ADC）和峰值强化百分比变化（DPE）均与曲妥珠单抗治疗后肿瘤浸润淋巴细胞的增加相关（相关系数r分别为-0.67和-0.69，p值均<0.01）。治疗前较低的ADC值以及治疗后强化百分比（PE）的更大程度降低，也与RNA免疫特征所定义的免疫激活的肿瘤微环境相关。乳腺MRI特征有望作为HER2阳性乳腺癌患者对治疗产生早期免疫反应的生物标志物。
肿瘤(癌症)患者之家