Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
International Cancer Prevention Institute, Epalinges, Switzerland.
Endocr Relat Cancer. 2018 May;25(5):R319-R330. doi: 10.1530/ERC-18-0063. Epub 2018 Mar 21.
Estrogen receptor-positive (ER+) tumors account for 70-80% of all breast cancer (BC) cases and are characterized by estrogen dependency for their growth. Endocrine therapies using estrogen receptor antagonists or aromatase inhibitors represent a key component of the standard of care for these tumors. The occurrence of de novo or acquired resistance to estrogen withdrawal represents an important clinical problem, impacting on patient survival. In addition, despite an initially favorable outcome, a part of ER+ BC patients present with disease recurrence locally or at distant sites years or even decades after apparent remission. models that closely mimic human disease are urgently needed to study the biology of these tumors, investigate the molecular mechanisms underlying endocrine resistance and identify patients at risk of recurrence. Despite the similarities in the overall hormonal regulation of mammary gland development between mice and humans, the majority of the mammary carcinomas occurring in genetically engineered mouse models (GEMMs) are ER negative and most xenograft models are based on few ER+ cancer cell lines. We recently showed that the microenvironment is critical for ER+ cancer cells and discuss in this review the potential of intraductal xenograft model for basic and preclinical research.
雌激素受体阳性（ER+）肿瘤占所有乳腺癌（BC）病例的 70-80%，其生长依赖于雌激素。使用雌激素受体拮抗剂或芳香化酶抑制剂的内分泌治疗是这些肿瘤标准治疗的重要组成部分。新出现的或获得性的对雌激素撤退的抵抗是一个重要的临床问题，影响患者的生存。此外，尽管最初的结果良好，但一部分 ER+BC 患者在明显缓解后数年甚至数十年，局部或远处出现疾病复发。迫切需要能够更紧密模拟人类疾病的模型来研究这些肿瘤的生物学特性，研究内分泌抵抗的分子机制，并确定有复发风险的患者。尽管在小鼠和人类中，乳腺发育的整体激素调节具有相似性，但大多数发生在基因工程小鼠模型（GEMMs）中的乳腺癌是 ER 阴性的，大多数异种移植模型都是基于少数 ER+癌细胞系。我们最近表明，微环境对 ER+癌细胞至关重要，本文讨论了管内异种移植模型在基础和临床前研究中的潜力。
