Department of Medicine, Stanford University School of Medicine, CA 94305-5820, USA.
Clin Breast Cancer. 2010;10 Suppl 1:E16-22. doi: 10.3816/CBC.2010.s.003.
Triple-negative breast cancers share an aggressive biology, marked by increased recurrence risk and poorer survival compared with hormone receptor-positive subtypes. Few therapeutic trials have specifically focused on triple-negative breast cancer, and the treatment of patients with early-stage triple-negative breast cancer has changed little in the past decade. Over this time, however, attention has shifted to treatment approaches based on molecular subtypes of breast cancer, and investigation into the mechanistic underpinnings of these distinct subtypes has exploded. Converging preclinical rationales combined with early provocative clinical efficacy has focused recent attention on strategies targeting DNA repair defects for the treatment of patients with triple-negative and BRCA mutation-associated breast cancers. These developments are very promising and suggest that major advances in the targeted treatment of patients with triple-negative breast cancer are in sight. This review provides an overview of the clinical features of triple-negative breast cancer and current treatment strategies in the adjuvant setting. Mechanisms of DNA repair and the DNA damage response are reviewed to provide background for understanding novel approaches targeting DNA repair defects in this disease with DNA-damaging chemotherapeutic agents and poly(ADP-ribose) polymerase inhibitors. Ongoing studies, including those investigating the role of antiangiogenic therapies, are also reviewed.
三阴性乳腺癌具有侵袭性生物学特征，与激素受体阳性亚型相比，其复发风险增加，生存率较低。很少有专门针对三阴性乳腺癌的治疗试验，过去十年中，早期三阴性乳腺癌患者的治疗方法变化不大。然而，在此期间，人们的注意力转向了基于乳腺癌分子亚型的治疗方法，对这些不同亚型的机制基础的研究也迅速增加。临床前合理的综合考虑，再加上早期有启发性的临床疗效，使人们最近关注针对 DNA 修复缺陷的策略，用于治疗三阴性和 BRCA 突变相关乳腺癌患者。这些进展非常有希望，表明针对三阴性乳腺癌患者的靶向治疗将取得重大进展。这篇综述概述了三阴性乳腺癌的临床特征和辅助治疗中的现有治疗策略。本文回顾了 DNA 修复机制和 DNA 损伤反应，为理解 DNA 损伤化学疗法和聚（ADP-核糖）聚合酶抑制剂靶向该疾病中 DNA 修复缺陷的新方法提供了背景。还回顾了正在进行的研究，包括抗血管生成治疗的作用研究。
