Corti Chiara, Koca Beyza, Rahman Tasnim, Mittendorf Elizabeth A, Tolaney Sara M
Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Immunotargets Ther. 2025 Apr 3;14:339-357. doi: 10.2147/ITT.S495751. eCollection 2025.
While immunotherapy has transformed treatment across various cancers, its impact on breast cancer is relatively limited. Recent advances have established immunotherapy as an effective approach for triple-negative breast cancer (TNBC), an aggressive subtype with limited therapeutic targets and poor prognosis. Specifically, pembrolizumab, an immune checkpoint inhibitor (ICI), is now approved for both first-line metastatic and early-stage TNBC. In metastatic TNBC, combining ICIs with chemotherapy, particularly pembrolizumab, has demonstrated survival benefits in patients with PD-L1-positive disease. However, extending these benefits to broader populations has proven challenging, highlighting the need for better patient selection and novel strategies. Emerging approaches include combining ICIs with antibody-drug conjugates, PARP inhibitors, dual ICIs, and bispecific antibodies targeting angiogenesis and immune checkpoints. These strategies aim to overcome resistance and expand immunotherapy's efficacy beyond the PD-1/PD-L1 pathway. In early-stage disease, pembrolizumab combined with chemotherapy in the neoadjuvant setting has significantly improved pathologic complete response, event-free survival, and overall survival, establishing a new standard of care. Ongoing research aims to determine the optimal timing for ICI administration, explore less toxic chemotherapy backbones, utilize biomarkers for personalized treatment, and assess whether adding complementary treatments, such as radiation therapy for high-risk cases, can improve outcomes. This review examines the successes and setbacks of ICI use in TNBC, offering a comprehensive overview of current practices and future directions. It emphasizes optimizing ICI timing, leveraging biomarkers, and integrating novel agents to refine treatment approaches for both metastatic and early-stage TNBC. As immunotherapy continues to evolve, future research must address the unmet needs of this challenging breast cancer subtype, offering hope for improved outcomes.
虽然免疫疗法已经改变了多种癌症的治疗方式,但其对乳腺癌的影响相对有限。最近的进展已将免疫疗法确立为三阴性乳腺癌(TNBC)的一种有效治疗方法,TNBC是一种侵袭性亚型,治疗靶点有限且预后较差。具体而言,免疫检查点抑制剂(ICI)派姆单抗现已获批用于一线转移性和早期TNBC。在转移性TNBC中,将ICI与化疗联合使用,尤其是派姆单抗,已证明对PD-L1阳性疾病患者有生存益处。然而,将这些益处扩展到更广泛的人群已被证明具有挑战性,这凸显了更好的患者选择和新策略的必要性。新兴方法包括将ICI与抗体药物偶联物、PARP抑制剂、双ICI以及靶向血管生成和免疫检查点的双特异性抗体联合使用。这些策略旨在克服耐药性,并将免疫疗法的疗效扩展到PD-1/PD-L1途径之外。在早期疾病中,派姆单抗在新辅助治疗中与化疗联合使用,显著改善了病理完全缓解率、无事件生存期和总生存期,确立了新的治疗标准。正在进行的研究旨在确定ICI给药的最佳时机,探索毒性较小的化疗方案,利用生物标志物进行个性化治疗,并评估添加补充治疗(如对高危病例进行放射治疗)是否能改善预后。本综述探讨了ICI在TNBC中应用的成功与挫折,全面概述了当前的实践和未来方向。它强调优化ICI的给药时机、利用生物标志物以及整合新型药物,以完善转移性和早期TNBC的治疗方法。随着免疫疗法不断发展,未来的研究必须解决这种具有挑战性的乳腺癌亚型尚未满足的需求,为改善预后带来希望。