作为癌症治疗最重要的突破之一，免疫检查点抑制剂极大地延长了乳腺癌患者的生存期。然而，它们的应用和疗效有限，特别是对于晚期 HER2 阴性乳腺癌。据报道，组蛋白脱乙酰酶（HDAC）抑制剂西达本胺的表观遗传调节以及放射治疗的免疫微环境调节可能与免疫治疗产生协同作用。因此，西达本胺、放疗和免疫治疗的联合治疗有望改善晚期 HER2 阴性乳腺癌患者的预后。这是一项单臂、开放、前瞻性临床试验，研究 HDAC 抑制剂西达本胺、抗 PD-1 抗体信迪利单抗，以及新型免疫放射疗法，旨在提高 HER2 阴性乳腺癌后续疗法中免疫疗法的疗效。我们的研究将包括 35 名内分泌治疗和一线化疗均失败的晚期乳腺癌患者。参与者将接受每周两次 30 毫克西达本胺，每 3 周一次 200 毫克信迪利单抗，并结合免疫放射治疗。至少一个病灶的放射治疗集中为 8 Gy，其他病灶的放射治疗至少为 1 Gy。我们将在一个周期内完成三个部分的放射治疗。主要终点是无进展生存期，次要终点是客观缓解率、疾病控制率和安全性。此外，还将探索包括细胞因子和淋巴细胞亚群在内的生物标志物。作为单臂临床试验，对每种单一治疗的影响的分析是有限的。此外，我们的研究是一项开放研究，既不涉及随机化，也不涉及盲法。尽管存在上述限制，这项前瞻性临床试验将深入了解 HER2 阴性晚期乳腺癌的后续治疗方案，延长这些参与者的生存期或实现长期缓解，并确定潜在的反应者。© 2024 张等人。

As one of the most important breakthroughs in cancer therapy, immune checkpoint inhibitors have greatly prolonged survival of patients with breast cancer. However, their application and efficacy are limited, especially for advanced HER2-negative breast cancer. It has been reported that epigenetic modulation of the histone deacetylase (HDAC) inhibitor chidamide, as well as immune microenvironment modulation of radiotherapy are potentially synergistic with immunotherapy. Thus, the combination of chidamide, radiotherapy and immunotherapy is expected to improve prognosis of patients with advanced HER2-negative breast cancer.This is a single-arm, open, prospective clinical trial investigating the efficacy and safety of the combination of HDAC inhibitor chidamide, anti-PD-1 antibody sintilimab, and the novel immuno-radiotherapy, which aims to enhance efficacy of immunotherapy, in subsequent lines of therapy of HER2-negative breast cancer. Our study will include 35 patients with advanced breast cancer that has failed endocrine therapy and first-line chemotherapy. Participants will receive 30 mg of chidamide twice a week, 200 mg of sintilimab once every 3 weeks, combined with immuno-radiotherapy. Radiotherapy will be centrally 8 Gy for at least one lesion, and at least 1 Gy for the other lesions. We will complete three fractions of radiotherapy in one cycle. The primary endpoint is progression-free survival, and secondary endpoints are objective response rate, disease control rate and safety. Moreover, biomarkers including cytokines and lymphocyte subgroups will be explored.As a single-arm clinical trial, the analysis of the influence of each single treatment is limited. Besides, our study is an open study, which involves neither randomization nor blinding. In spite of the abovementioned limitations, this prospective clinical trial will give an insight into subsequent lines of therapy of HER2-negative advanced breast cancer, prolong the survival or achieve long remission for these participants, and identify potential responders.© 2024 Zhang et al.