Clinical trials of immunotherapy in triple-negative breast cancer.
Clinical trials of immunotherapy in triple-negative breast cancer.
复制标题
三阴性乳腺癌免疫治疗的临床试验。
DOI：
10.1007/s10549-022-06665-6
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发表时间：
2022-08
影响因子：
3.8
通讯作者：
Nanda, Rita
中科院分区：
文献类型：
--
作者：
Howard, Frederick M.;Pearson, Alexander T.;Nanda, Rita
关键词：
免疫疗法已开始改变三阴性乳腺癌 (TNBC) 的治疗方法，部分原因是这种乳腺癌亚型具有独特的免疫原性。本综述总结了晚期和早期 TNBC 免疫治疗的临床研究。检查点阻断单一疗法的初步研究表明偶尔有缓解，特别是在未经治疗的程序性死亡配体 1 (PD-L1) 阳性晚期 TNBC 患者中，但未能证实相对于化疗的生存优势。尽管如此，派姆单抗单一疗法已获得与肿瘤无关的批准，用于治疗微卫星不稳定性高或高肿瘤突变负荷的癌症，因此可以考虑用于特定的晚期 TNBC 患者。联合化学免疫治疗方法更加成功，派姆单抗（pembrolizumab）被批准与化疗联合治疗 PD-L1 阳性晚期 TNBC。这一成功已转化为治疗领域，派姆单抗现已被批准与新辅助化疗联合治疗高危早期 TNBC。免疫疗法已成为不断增长的 TNBC 治疗方案中受欢迎的补充，但反应仍然仅限于一小部分患者。目前正在研究创新策略，试图通过结合小分子抑制剂、新型免疫检查点靶标和直接改变肿瘤微环境的瘤内注射的方案来诱导耐药肿瘤的免疫反应。随着焦点转向使用免疫疗法治疗早期 TNBC，鉴于潜在的不可逆自身免疫毒性以及早期环境中 PD-L1 表达缺乏预测准确性，确定哪些人能从治疗中获得最大益处至关重要。
Immunotherapy has started to transform the treatment of triple-negative breast cancer (TNBC), in part due to the unique immunogenicity of this breast cancer subtype. This review summarizes clinical studies of immunotherapy in advanced and early-stage TNBC. Initial studies of checkpoint blockade monotherapy demonstrated occasional responses, especially in patients with untreated programmed death-ligand 1 (PD-L1) positive advanced TNBC, but failed to confirm a survival advantage over chemotherapy. Nonetheless, pembrolizumab monotherapy has tumor agnostic approval for microsatellite instability-high or high tumor mutational burden cancers, and thus can be considered for select patients with advanced TNBC. Combination chemoimmunotherapy approaches have been more successful, and pembrolizumab is approved for PD-L1 positive advanced TNBC in combination with chemotherapy. This success has been translated to the curative setting, where pembrolizumab is now approved in combination with neoadjuvant chemotherapy for high-risk early-stage TNBC. Immunotherapy has been a welcome addition to the growing armamentarium for TNBC, but responses remain limited to a subset of patients. Innovative strategies are under investigation in an attempt to induce immune responses in resistant tumors—with regimens incorporating small-molecule inhibitors, novel immune checkpoint targets, and intratumoral injections that directly alter the tumor microenvironment. As the focus shifts toward the use of immunotherapy for early-stage TNBC, it will be critical to identify those who derive the most benefit from treatment, given the potential for irreversible autoimmune toxicity and the lack of predictive accuracy of PD-L1 expression in the early-stage setting.
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影响因子：
7.4
作者：
Brignone C;Gutierrez M;Mefti F;Brain E;Jarcau R;Cvitkovic F;Bousetta N;Medioni J;Gligorov J;Grygar C;Marcu M;Triebel F
通讯作者：
Triebel F
影响因子：
11.2
作者：
Burnette BC;Liang H;Lee Y;Chlewicki L;Khodarev NN;Weichselbaum RR;Fu YX;Auh SL
通讯作者：
Auh SL
影响因子：
45.3
作者：
Adams, Sylvia;Gray, Robert J.;Badve, Sunil S.
通讯作者：
Badve, Sunil S.
影响因子：
168.9
作者：
Cortes, Javier;Cescon, David W.;Schmid, Peter
通讯作者：
Schmid, Peter
影响因子：
50.5
作者：
Adams, S.;Dieras, V.;Schmid, P.
通讯作者：
Schmid, P.