Shaikh Saba S, Emens Leisha A
Department of Medicine, Division of Hematology and Oncology, University of Pittsburgh, Pittsburgh, PA, USA.
UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA.
Expert Opin Biol Ther. 2022 May;22(5):591-602. doi: 10.1080/14712598.2020.1801627. Epub 2020 Aug 9.
Triple negative breast cancer, defined by a lack of estrogen receptor, progesterone receptor, or human epidermal growth factor2, accounts for approximately 15% of breast cancer patients. Treatment options have historically been limited to chemotherapy, which has significant toxicity and a suboptimal impact on the five-year relapse rate and survival.
Transcriptomic analyses reveal that TNBC is biologically heterogenous. Predictive biomarkers based on the distinct biology of the different subtypes of TNBC should identify patients that will derive the greatest benefit from a specifically targeted therapeutic agent. Two biomarker-driven treatments have recently been approved: poly-ADP ribose polymerase inhibitors for patients with germline mutations and atezolizumab in combination with -paclitaxel for patients expressing PD-L1 on tumor-infiltrating immune cells.
Identifying informative predictive biomarkers is critical for the optimal development of targeted drugs for TNBC. Some targeted agents, such as the antibody-drug conjugate sacituzumab govitecan-hziy and the precision medicines capivasertib and ipatisertib, have already shown promising results in early clinical trials, and the results of definitive phase 3 trials are eagerly awaited. Additionally, testing novel immunotherapies and other targeted agents in earlier stages of disease, particularly the neoadjuvant setting, is a high priority.
三阴性乳腺癌是指缺乏雌激素受体、孕激素受体或人表皮生长因子2的乳腺癌,约占乳腺癌患者的15%。以往的治疗选择仅限于化疗,化疗具有显著的毒性,对五年复发率和生存率的影响也不尽人意。
转录组分析显示,三阴性乳腺癌在生物学上具有异质性。基于三阴性乳腺癌不同亚型独特生物学特性的预测性生物标志物,应能识别出从特定靶向治疗药物中获益最大的患者。最近有两种基于生物标志物的治疗方法获批:用于有胚系突变患者的聚腺苷二磷酸核糖聚合酶抑制剂,以及用于肿瘤浸润免疫细胞表达PD-L1患者的阿特珠单抗联合紫杉醇。
识别信息丰富的预测性生物标志物对于三阴性乳腺癌靶向药物的优化研发至关重要。一些靶向药物,如抗体药物偶联物戈沙妥珠单抗和精准药物卡匹西利和伊帕替尼,已在早期临床试验中显示出有前景的结果,人们急切期待最终的3期试验结果。此外,在疾病的早期阶段,特别是新辅助治疗阶段,测试新型免疫疗法和其他靶向药物是当务之急。