Ribeiro Rita, Carvalho Maria João, Goncalves João, Moreira João Nuno
CNC-Center for Neurosciences and Cell Biology, Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Faculty of Medicine (Polo 1), Coimbra, Portugal.
iMed.ULisboa-Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
Front Mol Biosci. 2022 Aug 19;9:903065. doi: 10.3389/fmolb.2022.903065. eCollection 2022.
Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer that represents 15-20% of breast tumors and is more prevalent in young pre-menopausal women. It is the subtype of breast cancers with the highest metastatic potential and recurrence at the first 5 years after diagnosis. In addition, mortality increases when a complete pathological response is not achieved. As TNBC cells lack estrogen, progesterone, and HER2 receptors, patients do not respond well to hormone and anti-HER2 therapies, and conventional chemotherapy remains the standard treatment. Despite efforts to develop targeted therapies, this disease continues to have a high unmet medical need, and there is an urgent demand for customized diagnosis and therapeutics. As immunotherapy is changing the paradigm of anticancer treatment, it arises as an alternative treatment for TNBC patients. TNBC is classified as an immunogenic subtype of breast cancer due to its high levels of tumor mutational burden and presence of immune cell infiltrates. This review addresses the implications of these characteristics for the diagnosis, treatment, and prognosis of the disease. Herein, the role of immune gene signatures and tumor-infiltrating lymphocytes as biomarkers in TNBC is reviewed, identifying their application in patient diagnosis and stratification, as well as predictors of efficacy. The expression of PD-L1 expression is already considered to be predictive of response to checkpoint inhibitor therapy, but the challenges regarding its value as biomarker are described. Moreover, the rationales for different formats of immunotherapy against TNBC currently under clinical research are discussed, and major clinical trials are highlighted. Immune checkpoint inhibitors have demonstrated clinical benefit, particularly in early-stage tumors and when administered in combination with chemotherapy, with several regimens approved by the regulatory authorities. The success of antibody-drug conjugates and research on other emerging approaches, such as vaccines and cell therapies, will also be addressed. These advances give hope on the development of personalized, more effective, and safe treatments, which will improve the survival and quality of life of patients with TNBC.
三阴性乳腺癌（TNBC）是一种临床上具有侵袭性的乳腺癌亚型，占乳腺肿瘤的15%-20%，在绝经前年轻女性中更为常见。它是乳腺癌中转移潜力最高且在诊断后前5年复发率最高的亚型。此外，如果未实现完全病理缓解，死亡率会增加。由于TNBC细胞缺乏雌激素、孕激素和HER2受体，患者对激素和抗HER2治疗反应不佳，传统化疗仍是标准治疗方法。尽管努力开发靶向治疗，但这种疾病仍存在高度未满足的医疗需求，迫切需要定制化的诊断和治疗方法。随着免疫疗法正在改变抗癌治疗模式，它成为TNBC患者的一种替代治疗方法。由于TNBC具有高水平的肿瘤突变负荷和免疫细胞浸润，它被归类为乳腺癌的免疫原性亚型。本综述阐述了这些特征对该疾病诊断、治疗和预后的影响。在此，综述了免疫基因特征和肿瘤浸润淋巴细胞作为TNBC生物标志物的作用，确定它们在患者诊断和分层中的应用以及疗效预测指标。PD-L1表达已被认为可预测对检查点抑制剂治疗的反应，但也描述了其作为生物标志物的价值所面临的挑战。此外，讨论了目前正在临床研究的针对TNBC的不同免疫治疗形式的基本原理，并重点介绍了主要临床试验。免疫检查点抑制剂已显示出临床益处，特别是在早期肿瘤中以及与化疗联合使用时，有几种方案已获得监管机构批准。抗体药物偶联物的成功以及对其他新兴方法（如疫苗和细胞疗法）的研究也将得到探讨。这些进展为开发个性化、更有效和安全的治疗方法带来了希望，这将改善TNBC患者的生存率和生活质量。
