Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA.
Department of Medical Oncology, Instituto Nacional de Câncer (INCA), Praça da Cruz Vermelha, 23, 20230-130, Rio de Janeiro, Brazil.
Nat Rev Cancer. 2015 May;15(5):261-75. doi: 10.1038/nrc3920.
Oestrogen receptor-positive (ER(+)) breast cancer is a major cause of cancer death in women. Although aromatase inhibitors suppress the function of ER and reduce the risk of recurrence, therapeutic resistance is common and essentially inevitable in advanced disease. This Review considers both genomic and cell biological explanations as to why ER(+) breast cancer cells persist, progress and cause an incurable, lethal, systemic disease. The design and outcomes of clinical trials are considered with the perspective that resistance mechanisms are heterogeneous, and therefore biomarker and somatic mutation-based stratification and eligibility will be essential for improvements in patient outcomes.
雌激素受体阳性（ER(+））乳腺癌是女性癌症死亡的主要原因。尽管芳香酶抑制剂抑制 ER 的功能并降低复发风险，但在晚期疾病中，治疗耐药性很常见，而且几乎不可避免。本综述考虑了 ER(+)乳腺癌细胞持续存在、进展并导致无法治愈、致命的全身性疾病的基因组和细胞生物学解释。考虑到耐药机制具有异质性，临床试验的设计和结果认为基于生物标志物和体细胞突变的分层和资格将是改善患者预后的关键。
