Dana Farber Cancer Institute, Boston, MA 02215, USA.
St. Elizabeth's Medical Center, Boston, MA 02111, USA.
Int J Mol Sci. 2024 Jul 9;25(14):7517. doi: 10.3390/ijms25147517.
Breast cancer is a disease encompassing a spectrum of molecular subtypes and clinical presentations, each with distinct prognostic implications and treatment responses. Breast cancer has traditionally been considered an immunologically "cold" tumor, unresponsive to immunotherapy. However, clinical trials in recent years have found immunotherapy to be an efficacious therapeutic option for select patients. Breast cancer is categorized into different subtypes ranging from the most common positive hormone receptor (HR+), human epidermal growth factor receptor 2 (HER2)-negative type, to less frequent HER2- positive breast cancer and triple-negative breast cancer (TNBC), highlighting the necessity for tailored treatment strategies aimed at maximizing patient outcomes. Despite notable progress in early detection and new therapeutic modalities, breast cancer remains the second leading cause of cancer death in the USA. Moreover, in recent decades, breast cancer incidence rates have been increasing, especially in women younger than the age of 50. This has prompted the exploration of new therapeutic approaches to address this trend, offering new therapeutic prospects for breast cancer patients. Immunotherapy is a class of therapeutic agents that has revolutionized the treatment landscape of many cancers, namely melanoma, lung cancer, and gastroesophageal cancers, amongst others. Though belatedly, immunotherapy has entered the treatment armamentarium of breast cancer, with the approval of pembrolizumab in combination with chemotherapy in triple-negative breast cancer (TNBC) in the neoadjuvant and advanced settings, thereby paving the path for further research and integration of immune checkpoint inhibitors in other subtypes of breast cancer. Trials exploring various combination therapies to harness the power of immunotherapy in symbiosis with various chemotherapeutic agents are ongoing in hopes of improving response rates and prolonging survival for breast cancer patients. Biomarkers and precise patient selection for the utilization of immunotherapy remain cardinal and are currently under investigation, with some biomarkers showing promise, such as Program Death Lignat-1 (PDL-1) Combined Positive Score, Tumor Mutation Burden (TMB), and Tumor Infiltrating Lymphocytes (TILs). This review will present the current landscape of immunotherapy, particularly checkpoint inhibitors, in different types of breast cancer.
乳腺癌是一种涵盖多种分子亚型和临床表现的疾病，每种亚型都有不同的预后意义和治疗反应。乳腺癌传统上被认为是一种免疫“冷”肿瘤，对免疫疗法无反应。然而，近年来的临床试验发现，免疫疗法是一种针对特定患者有效的治疗选择。乳腺癌分为不同的亚型，从最常见的阳性激素受体（HR+）、人表皮生长因子受体 2（HER2）阴性型，到不太常见的 HER2 阳性乳腺癌和三阴性乳腺癌（TNBC），突出了针对不同亚型的个体化治疗策略的必要性，以最大限度地提高患者的治疗效果。尽管在早期检测和新的治疗方法方面取得了显著进展，但乳腺癌仍是美国第二大癌症死亡原因。此外，近几十年来，乳腺癌的发病率一直在上升，尤其是在 50 岁以下的女性中。这促使人们探索新的治疗方法来应对这一趋势，为乳腺癌患者提供新的治疗前景。免疫疗法是一类治疗药物，它彻底改变了许多癌症的治疗格局，如黑色素瘤、肺癌和胃食管癌症等。虽然有点迟，但免疫疗法已经进入了乳腺癌的治疗武器库，批准了帕博利珠单抗联合化疗用于三阴性乳腺癌（TNBC）的新辅助和晚期治疗，从而为进一步研究和整合免疫检查点抑制剂在其他乳腺癌亚型中的应用铺平了道路。目前正在进行各种联合治疗试验，以利用免疫疗法与各种化疗药物的协同作用，希望提高乳腺癌患者的反应率和延长生存期。生物标志物和精确的患者选择仍然是免疫疗法的关键，目前正在研究中，一些生物标志物显示出希望，如程序性死亡配体 1（PDL-1）联合阳性评分、肿瘤突变负荷（TMB）和肿瘤浸润淋巴细胞（TILs）。这篇综述将介绍免疫疗法，特别是检查点抑制剂在不同类型乳腺癌中的最新进展。
