Memorial Sloan Kettering Cancer Center, New York, NY.
Memorial Sloan Kettering Cancer Center, New York, NY.
Clin Breast Cancer. 2023 Dec;23(8):784-799. doi: 10.1016/j.clbc.2023.05.012. Epub 2023 May 28.
Triple negative breast cancer (TNBC) remains the subtype with poorest prognosis. Despite the subtype's heterogeneity, there is still a paucity in effective targeted therapeutics that offer both good efficacy and tolerability, and chemotherapy remains the backbone of modern TNBC therapy. In the past few years, immunotherapy as well as novel therapeutic modalities like antibody-drug conjugates (ADCs) have shown clinical benefit and have been FDA approved in various clinical stages of unselected TNBC. However, there has not been similar advancement in molecularly targeted therapies, especially when compared to advancements seen in hormone receptor (HR)-positive or HER2-positive breast cancer. PARP inhibitors have been approved for BRCA-mutated TNBC, but responses are short-lived, and resistance remains a barrier for current treatment. PI3K pathway inhibitors approved in HR+ breast cancer has not worked for TNBC and continue to have significant dose-limiting adverse effects. EGFR inhibition has been thoroughly explored in TNBC, but all trials so far have shown minimal efficacy. Nevertheless, despite these setbacks, current research in targeted therapy for TNBC holds great promise in overcoming the barriers of the past and developing novel therapeutic approaches for the future. In this review, we describe molecular targets both identified and validated in the treatment of TNBC, discuss the historical efforts towards development of targeted agents and current areas of improvement, and address promising advances that have the potential to improve outcomes in this heterogenous and aggressive breast cancer subtype. Immunotherapy, ADCs, and AR targeting will be discussed in separate reviews of this edition.
三阴性乳腺癌（TNBC）仍然是预后最差的亚型。尽管该亚型具有异质性，但仍然缺乏有效且耐受良好的靶向治疗药物，化疗仍然是现代 TNBC 治疗的基础。在过去几年中，免疫疗法以及抗体药物偶联物（ADC）等新型治疗方式已显示出临床获益，并已在未经选择的 TNBC 的各个临床阶段获得 FDA 批准。然而，在分子靶向治疗方面并没有类似的进展，尤其是与激素受体（HR）阳性或 HER2 阳性乳腺癌相比。PARP 抑制剂已获批用于 BRCA 突变型 TNBC，但反应持续时间短，且耐药性仍然是当前治疗的障碍。在 HR+乳腺癌中获批的 PI3K 通路抑制剂对 TNBC 无效，并且仍然存在显著的剂量限制不良反应。EGFR 抑制在 TNBC 中进行了深入研究，但迄今为止所有试验的疗效都很有限。尽管存在这些挫折，但目前针对 TNBC 的靶向治疗研究在克服过去的障碍和为未来开发新的治疗方法方面具有巨大的潜力。在这篇综述中，我们描述了在 TNBC 治疗中已确定和验证的分子靶点，讨论了针对这些靶点开发靶向药物的历史努力和当前的改进领域，并探讨了有潜力改善这种异质性和侵袭性乳腺癌亚型患者预后的有希望的进展。免疫疗法、ADC 和 AR 靶向将在这一版的单独综述中进行讨论。
