Academic Trials Promoting Team, Institut Jules Bordet and l'Université Libre de Bruxelles (U.L.B), Bruxelles, Belgium.
Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy.
Expert Opin Investig Drugs. 2022 Jun;31(6):567-591. doi: 10.1080/13543784.2022.2049232. Epub 2022 Mar 9.
Triple negative breast cancer (TNBC) is an area of high unmet medical need in terms of new effective treatment strategies. Although breast cancer is traditionally considered a 'cold' tumor type, TNBC is the most appropriate subtype for immunotherapeutic strategies; this is due to the high level of tumor infiltrating lymphocytes, PD-L1 expression, and tumor mutational burden compared to other breast cancer subtypes.
This review examines the available evidence on the use of immunotherapeutic strategies in early and advanced TNBC, discusses the pitfalls and limitations often encountered in clinical research, and summarizes data on novel promising immunomodulatory approaches that have been explored in early-phase trials.
PD-1-blockade is approved for stage II/III TNBC and for first-line treatment of PD-L1-positive TNBC patients with metastatic disease and should be considered standard of care. However, question marks and difficulties remain; these include the identification of predictive biomarkers to select patients who benefit from the addition of PD1-blockade and the balance between efficacy and long-term toxicity for an individual patient. Numerous treatment combinations and new immunotherapeutic strategies beyond PD1 blockade are being evaluated, thus reflecting a promising evolution towards a more personalized approach, and extended clinical benefit in TNBC.Triple-negative breast cancer (TNBC); breast cancers (BCs); estrogen receptor (ER); progesterone receptor (PgR); human epidermal growth factor-2 (HER-2); basal-like 1 (BL1), basal-like 2 (BL2); mesenchymal (MES); mesenchymal stem-like (MSL); immunomodulatory (IM); luminal androgen receptor (LAR); basal-like immunosuppressed (BLIS); basal-like immune-activated (BLIA); tumor-infiltrating lymphocytes (TILs); tumor mutational burden (TMB); immune cells (ICs); immunohistochemistry (IHC); overall response rate (ORR); overall survival (OS); progression-free survival (PFS); intention-to-treat (ITT); hazard ratio (HR); confidence interval (CI); Food and Drug Administration (FDA); European Medicines Agency (EMA); immune checkpoint inhibitors (ICI); Combined Positive Score (CPS); disease control rate (DCR); neoadjuvant chemotherapy (NACT); pathological complete response (pCR); event-free survival (EFS); disease-free survival (DFS); residual cancer burden (RCB); San Antonio Breast Cancer Symposium (SABCS); antibody-drug conjugates (ADCs); PARP inhibitors (PARPi); clinical benefit rate (CBR); Histone deacetylase inhibitors (HDACi); Dendritic cell (DC); talimogene laherparepvec (TVEC); granulocyte-macrophage colony-stimulating factor (GM-CSF); mismatch repair deficiency (dMMR).
三阴性乳腺癌（TNBC）在新的有效治疗策略方面存在着高度未满足的医学需求。尽管乳腺癌传统上被认为是一种“冷”肿瘤类型，但 TNBC 是最适合免疫治疗策略的亚型；这是由于与其他乳腺癌亚型相比，TNBC 具有更高水平的肿瘤浸润淋巴细胞、PD-L1 表达和肿瘤突变负担。
本文综述了免疫治疗策略在早期和晚期 TNBC 中的应用，讨论了临床研究中经常遇到的陷阱和局限性，并总结了在早期试验中探索的新型有前途的免疫调节方法的数据。
PD-1 阻断剂已被批准用于 II/III 期 TNBC 和 PD-L1 阳性转移性 TNBC 患者的一线治疗，应被视为标准治疗。然而，仍存在疑问和困难；这些包括确定预测生物标志物以选择从 PD1 阻断中获益的患者，以及平衡个体患者的疗效和长期毒性。目前正在评估许多治疗组合和新的免疫治疗策略，除了 PD1 阻断，这反映了朝着更个性化方法的有希望的发展，并在 TNBC 中延长了临床获益。三阴性乳腺癌（TNBC）；乳腺癌（BCs）；雌激素受体（ER）；孕激素受体（PgR）；人表皮生长因子-2（HER-2）；基底样 1（BL1），基底样 2（BL2）；间充质（MES）；间充质干细胞样（MSL）；免疫调节（IM）；亮氨酸雄激素受体（LAR）；基底样免疫抑制（BLIS）；基底样免疫激活（BLIA）；肿瘤浸润淋巴细胞（TILs）；肿瘤突变负担（TMB）；免疫细胞（ICs）；免疫组织化学（IHC）；总缓解率（ORR）；总生存期（OS）；无进展生存期（PFS）；意向治疗（ITT）；风险比（HR）；置信区间（CI）；食品和药物管理局（FDA）；欧洲药品管理局（EMA）；免疫检查点抑制剂（ICI）；联合阳性评分（CPS）；疾病控制率（DCR）；新辅助化疗（NACT）；病理完全缓解（pCR）；无事件生存期（EFS）；无病生存期（DFS）；残留肿瘤负荷（RCB）；圣安东尼奥乳腺癌研讨会（SABCS）；抗体药物偶联物（ADCs）；聚 ADP 核糖聚合酶抑制剂（PARPi）；临床获益率（CBR）；组蛋白去乙酰化酶抑制剂（HDACi）；树突状细胞（DC）；替莫唑胺拉帕鲁昔帕尼（TVEC）；粒细胞-巨噬细胞集落刺激因子（GM-CSF）；错配修复缺陷（dMMR）。
