晚期三阴性乳腺癌生物标志物的叙述性回顾

R. Chehade, A. Awan, R. Fernandes
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摘要

三阴性乳腺癌(TNBC)是一种异质性疾病;虽然临床上诊断为单一实体疾病,但在分子水平上,TNBC包括具有亚型特异性靶向治疗潜力的特征性亚型,这些治疗仍在进行中。化疗仍然是治疗TNBC的主要方法。尽管在转移性肿瘤中已经引入了新的靶向治疗,包括免疫治疗、PARP抑制剂和抗体药物偶联物(ADC),但在更好地了解TNBC亚型生物学的基础上,确定有选择地从这些治疗中获益的患者仍有待更精细的选择过程。更重要的是,需要一种经过验证的基因组精度和生物标志物驱动的靶向治疗工具,以便在临床中容易地识别TNBC亚型,并将复杂的分子分析转化为患者的个性化治疗计划。本综述介绍了晚期TNBC中具有靶向治疗潜力的生物标志物,并讨论了管理TNBC异质性的持续策略。我们讨论的生物标志物包括TP53、雄激素受体、乳腺癌易感基因(BRCA)、同源重组缺陷(HRD)、PI3K/AKT/mTOR、免疫生物标志物和ADC。该综述总结了生物标志物驱动的靶向治疗在晚期TNBC中的前景,这些治疗已经改善了这种侵袭性疾病的预后。
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A narrative review of biomarkers in advanced triple negative breast cancer
Triple negative breast cancer (TNBC) is a heterogeneous disease; while clinically diagnosed as a single entity disease, at the molecular level, TNBC includes characteristic subtypes with potential for subtype specific targeted therapies which are still underway. Chemotherapy remains the backbone of treatment of TNBC. Although new targeted therapies have been introduced in the metastatic setting, including immunotherapy, PARP inhibitors and antibody drug conjugates (ADC), identifying patients who would selectively benefit from these treatments is awaiting a more refined selection process driven by better understanding of the biology of TNBC subtypes. More importantly, there is a need for validated tools of genomic precision and biomarker driven targeted therapy that can readily identify TNBC subtypes in the clinic and translate complex molecular analysis into individualized treatment plans for patients. This review presents biomarkers in advanced TNBC with potential for targeted therapies and discusses ongoing strategies to managing the heterogeneity of TNBCs. We discuss biomarkers including TP53, androgen receptor, breast cancer susceptibility genes (BRCA), homologous recombination deficiency (HRD), PI3K/AKT/mTOR, immune biomarkers, and ADC. The review concludes with a summary of the landscape of biomarker driven targeted therapies in advanced TNBC that has been improving outcomes of this aggressive disease.
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