Breast Cancer Center, Medical Oncology Department, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, 08035 Barcelona, Spain.
Nat Rev Clin Oncol. 2010 Mar;7(3):139-47. doi: 10.1038/nrclinonc.2009.234. Epub 2010 Feb 2.
Breast cancer is a heterogeneous disease with different molecular drivers regulating its growth, survival and response to therapy. Breast cancer is divided in three major subtypes based on the pattern of expression of hormone receptors and HER2: luminal tumors (or HR positive), HER2 amplified tumors, and the remaining subtypes being collectively referred to as triple-negative breast cancer. While tumors within these subtypes have similar gene-expression patterns, clinical outcomes, and response to therapy, this division is far from perfect and subgroups within these groups are beginning to be identified. In terms of therapy, an increasingly rational drug development effort has resulted in agents against new molecular targets that are active against only those tumors with the targeted molecular alteration or phenotype. These agents include receptor and non-receptor tyrosine kinase inhibitors (HER1, HER2, HER3, insulin-like growth factor receptor, c-met, fibroblast growth factor receptor and HSP 90 inhibitors), intracellular signaling pathways (PI3K, AKT, mTOR), angiogenesis inhibitors and agents that interfere with DNA repair (PARP inhibitors). Thus, the overall management of breast cancer will increasingly require an understanding of breast cancer heterogeneicity, the biological nature of any given tumor as well the existence of increased personalized treatment options.
乳腺癌是一种异质性疾病，不同的分子驱动因素调节其生长、存活和对治疗的反应。根据激素受体和 HER2 的表达模式，乳腺癌分为三种主要亚型：腔肿瘤（或 HR 阳性）、HER2 扩增肿瘤，以及其余被统称为三阴性乳腺癌的亚型。尽管这些亚型内的肿瘤具有相似的基因表达模式、临床结果和对治疗的反应，但这种分类远非完美，这些组内的亚组开始被识别。在治疗方面，针对新分子靶点的药物开发工作日益合理化，这些药物针对的是仅具有靶向分子改变或表型的肿瘤。这些药物包括受体和非受体酪氨酸激酶抑制剂（HER1、HER2、HER3、胰岛素样生长因子受体、c-met、成纤维细胞生长因子受体和 HSP90 抑制剂）、细胞内信号通路（PI3K、AKT、mTOR）、血管生成抑制剂和干扰 DNA 修复的药物（PARP 抑制剂）。因此，乳腺癌的整体管理将越来越需要了解乳腺癌的异质性、任何给定肿瘤的生物学性质以及存在更多个性化治疗选择。
