a National Center for Tumor Diseases, Department of Medical Oncology , University of Heidelberg , Heidelberg , Germany.
Expert Rev Anticancer Ther. 2019 Jan;19(1):29-42. doi: 10.1080/14737140.2019.1537785. Epub 2018 Oct 29.
: Accounting for about 15% of breast cancer patients, triple-negative breast cancer (TNBC) is responsible for 25% of disease related deaths, more frequent distant spread and visceral metastasis. However, improving survival in TNBC failed and primary resistance, immunological ignorance and tumor heterogeneity limit clinical activity of novel therapies. In view of recent molecular, genetic and immunologic insights, this review aims to describe the current status of immunological and targeted treatments from a hypothesis driven perspective. : Recent preclinical studies and ongoing clinical trials for immune directed and targeted treatments of TNBC are summarized, including immune-checkpoint blockade, resistance mechanisms, inhibition of poly (ADP-ribose) polymerase (PARP), combinatorial strategies as well as preclinical, hypothesis generating studies. : Sustained responses have been observed with immune-checkpoint blockade and PARP inhibitors demonstrated remarkable efficacy in germline BRCA mutated TNBC. In order to generate clinical success of many other, to date ineffective, targeted and immune therapies, the integration of multidimensional, large amounts of data, will be essential and likely accelerate treatment progress of TNBC.
三阴性乳腺癌(TNBC)约占乳腺癌患者的 15%,其导致了 25%的与疾病相关的死亡,更频繁的远处扩散和内脏转移。然而,改善 TNBC 的生存率的尝试并未成功,原发性耐药、免疫忽视和肿瘤异质性限制了新型治疗方法的临床疗效。鉴于最近的分子、遗传和免疫学的深入了解,本综述旨在从假设驱动的角度描述当前免疫和靶向治疗的现状。
本文总结了最近针对 TNBC 的免疫和靶向治疗的临床前研究和正在进行的临床试验,包括免疫检查点阻断、耐药机制、多聚(ADP-核糖)聚合酶(PARP)抑制剂、联合策略以及临床前、产生假说的研究。
免疫检查点阻断和 PARP 抑制剂的持续反应已经被观察到,在种系 BRCA 突变的 TNBC 中显示出显著的疗效。为了使许多其他目前无效的靶向和免疫治疗方法取得临床成功,整合多维、大量的数据将是至关重要的,并且可能会加速 TNBC 的治疗进展。