Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Anticancer Agents Med Chem. 2022;22(4):787-800. doi: 10.2174/1871520621666210706144112.
Immune Checkpoint Inhibitors (ICIs) have remarkably modified the way solid tumors are managed, including breast cancer. Unfortunately, only a relatively small number of breast cancer patients significantly respond to these treatments. To maximize the immunotherapy benefit in breast cancer, several efforts are currently being put forward for the identification of i) the best therapeutic strategy (i.e. ICI monotherapy or in association with chemotherapy, radiotherapy, or other drugs); ii) optimal timing for administration (e.g. early/advanced stage of disease; adjuvant/ neoadjuvant setting); iii) most effective and reliable predictive biomarkers of response (e.g. tumor-infiltrating lymphocytes, programmed death-ligand 1, microsatellite instability associated with mismatch repair deficiency, and tumor mutational burden). In this article, we review the impacts and gaps in the characterization of immune-related biomarkers raised by clinical and translational research studies with immunotherapy treatments. Particular emphasis has been put on the documented evidence of significant clinical benefits of ICI in different randomized clinical trials, along with preanalytical and analytical issues in predictive biomarkers pathological assessment.
免疫检查点抑制剂（ICIs）显著改变了实体瘤的治疗方式，包括乳腺癌。不幸的是，只有相对较少的乳腺癌患者对这些治疗有显著反应。为了最大限度地提高乳腺癌的免疫治疗效益，目前正在进行多项努力，以确定：i）最佳治疗策略（即 ICI 单药治疗或与化疗、放疗或其他药物联合治疗）；ii）最佳给药时机（例如疾病的早期/晚期；辅助/新辅助治疗）；iii）最有效和可靠的反应预测生物标志物（例如肿瘤浸润淋巴细胞、程序性死亡配体 1、与错配修复缺陷相关的微卫星不稳定性和肿瘤突变负担）。本文综述了免疫治疗相关生物标志物的临床和转化研究对免疫相关生物标志物的特征的影响和差距。特别强调了不同随机临床试验中 ICI 具有显著临床获益的已有证据，以及预测生物标志物病理评估中的分析前和分析问题。
