Reis-Filho J S, Tutt A N J
The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.
Histopathology. 2008 Jan;52(1):108-18. doi: 10.1111/j.1365-2559.2007.02889.x.
Breast cancer is a heterogeneous disease that encompasses several distinct entities with remarkably different biological characteristics and clinical behaviour. Currently, breast cancer patients are managed according to algorithms based on a constellation of clinical and histopathological parameters in conjunction with assessment of hormone receptor (oestrogen and progesterone receptor) status and HER2 overexpression/gene amplification. Although effective tailored therapies have been developed for patients with hormone receptor-positive or HER2+ disease, chemotherapy is the only modality of systemic therapy for patients with breast cancers lacking the expression of these markers (triple-negative cancers). Recent microarray expression profiling analyses have demonstrated that breast cancers can be systematically characterized into biologically and clinically meaningful groups. These studies have led to the re-discovery of basal-like breast cancers, which preferentially show a triple-negative phenotype. Both triple-negative and basal-like cancers preferentially affect young and African-American women, are of high histological grade and have more aggressive clinical behaviour. Furthermore, a significant overlap between the biological and clinical characteristics of sporadic triple-negative and basal-like cancers and breast carcinomas arising in BRCA1 mutation carriers has been repeatedly demonstrated. In this review, we critically address the characteristics of basal-like and triple-negative cancers, their similarities and differences, their response to chemotherapy as well as strategies for the development of novel therapeutic targets for these aggressive types of breast cancer. In addition, the possible mechanisms are discussed leading to BRCA1 pathway dysfunction in sporadic triple-negative and basal-like cancers and animal models for these tumour types.
乳腺癌是一种异质性疾病，包含几种具有显著不同生物学特征和临床行为的不同实体。目前，乳腺癌患者是根据基于一系列临床和组织病理学参数并结合激素受体（雌激素和孕激素受体）状态及HER2过表达/基因扩增评估的算法来进行管理的。尽管已经为激素受体阳性或HER2阳性疾病的患者开发了有效的个体化治疗方法，但化疗是缺乏这些标志物表达的乳腺癌患者（三阴性乳腺癌）唯一的全身治疗方式。最近的微阵列表达谱分析表明，乳腺癌可以被系统地分为具有生物学和临床意义的组。这些研究导致了基底样乳腺癌的重新发现，其优先表现出三阴性表型。三阴性和基底样癌都优先影响年轻女性和非裔美国女性，组织学分级高，临床行为更具侵袭性。此外，散发性三阴性和基底样癌与BRCA1突变携带者发生的乳腺癌在生物学和临床特征上的显著重叠已被反复证实。在这篇综述中，我们批判性地探讨了基底样和三阴性癌的特征、它们的异同、它们对化疗的反应以及针对这些侵袭性乳腺癌类型开发新型治疗靶点的策略。此外，还讨论了散发性三阴性和基底样癌中导致BRCA1通路功能障碍的可能机制以及这些肿瘤类型的动物模型。
