近年来肿瘤免疫治疗(cancer immunotherapy, CIT)的发展使恶性肿瘤的治疗模式发生转变,尤其是黑色素瘤、肾癌、膀胱癌和肺癌,其显著提高了肿瘤的治疗敏感性,延长患者总生存时间(overall survival, OS)。乳腺癌通常被认为是一种“非炎症性”癌症,因此这种转变在治疗过程中没有那么明显。然而,一些乳腺癌的亚型,尤其是三阴性乳腺癌(Triple negative breast cancer, TNBC),多被认为是“炎症”,因此可能被证明是适合CIT的群体。本文回顾了肿瘤免疫周期理论和免疫抑制点的作用机制,就乳腺癌免疫治疗的研究进展及发现的问题进行综述。 Over the last few years, the developments around cancer immunotherapy (CIT) have led to a pa-radigm shift in the treatment of many different cancers, in particular melanoma, renal, bladder and lung cancers with a remarkable impact on response rate and, most importantly, overall survival. Breast cancer is most commonly considered to be a “non-inflamed” cancer and so this shift has been less marked within its treatment. However, some subsets of breast cancer, most notably triple negative breast cancer, are deemed to be more “inflamed” and therefore may prove to be an appropriate cohort for CIT. This review looks back at the theory of the cancer immunity cycle and mechanism of action behind immune checkpoint inhibitors and goes on to explore their roles in breast cancer, especially triple negative breast cancer.
免疫治疗,联合治疗,乳腺癌, Immunotherapy Combination Therapy Breast Cancer乳腺癌免疫治疗新进展
徐小萌1,韩真真2,袁胜利2*
1青岛大学医学院,山东 青岛
2青岛市市立医院肿瘤科,山东 青岛
收稿日期:2018年2月6日;录用日期:2018年2月20日;发布日期:2018年2月27日
摘 要
近年来肿瘤免疫治疗(cancer immunotherapy, CIT)的发展使恶性肿瘤的治疗模式发生转变,尤其是黑色素瘤、肾癌、膀胱癌和肺癌,其显著提高了肿瘤的治疗敏感性,延长患者总生存时间(overall survival, OS)。乳腺癌通常被认为是一种“非炎症性”癌症,因此这种转变在治疗过程中没有那么明显。然而,一些乳腺癌的亚型,尤其是三阴性乳腺癌(Triple negative breast cancer, TNBC),多被认为是“炎症”,因此可能被证明是适合CIT的群体。本文回顾了肿瘤免疫周期理论和免疫抑制点的作用机制,就乳腺癌免疫治疗的研究进展及发现的问题进行综述。
目前,在TNBC中临床数据较多的是PD-L1抑制剂Atezolizumab,在2017年美国癌症研究协会(American Association for Cancer Research)年会上,Schmid等 [23] 公布了一项Atezolizumab单药治疗转移性TNBC的I期临床试验结果。本试验共纳入115例患者,最初只选取免疫细胞5% PD-L1表达的患者,但随后也纳入了PD-L1低表达或表达缺失的患者。入组患者中,17%既往接受过一线治疗,24%的患者在转移前接受过1次治疗,58%接受2次治疗。98例(85%)、108例(94%)和67例(58%)患者分别接受过蒽环类、紫杉类和铂类为基础的化疗。根据RECIST标准评价,Atzolizumab治疗后患者的客观缓解率(Objective Response Rate, ORR)为10%,根据改良的RECIST标准评价,患者ORR为13%。此外,接受Atzolizumab一线CIT治疗的患者,ORR为26%,接受二线治疗的患者,ORR为4%,而接受三线及以上治疗的患者,ORR为8%。根据上述研究结果,我们认为,患者越是早期治疗,对CIT的反应越高。而这项研究也是目前乳腺癌免疫治疗随访时间最长的一项研究,接受Atzolizumab一线治疗的患者,1年及2年整体生存率分别为63%及47%,而接受2线及2线以上治疗的患者,1年及2年的整体生存率则分别为37%及18%。
徐小萌,韩真真,袁胜利. 乳腺癌免疫治疗新进展New Progress in Breast Cancer Immunotherapy[J]. 临床医学进展, 2018, 08(01): 47-52. http://dx.doi.org/10.12677/ACM.2018.81009
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