Sikora Matthew J, Jankowitz Rachel C, Dabbs David J, Oesterreich Steffi
Department of Pharmacology and Chemical Biology, University of Pittsburgh, United States.
Steroids. 2013 Jun;78(6):568-75. doi: 10.1016/j.steroids.2012.11.002. Epub 2012 Nov 21.
Invasive lobular carcinoma of the breast (ILC) represents 10-15% of all newly diagnosed breast cancers, affecting ∼30,000 women annually in the United States. However, ILC is critically understudied as a breast cancer subtype. Though the vast majority of ILC are estrogen receptor-positive and present with overall favorable biomarkers, ILC patients do not benefit from improved outcomes versus other breast cancer patients. Patient outcomes, in particular in response to endocrine therapies, are not well understood in ILC, due in large part to the lack of prospective identification in large clinical trials. Further, there is a lack of laboratory models to study cell signaling, hormone response, and endocrine resistance in ILC. In this review, we provide an overview of clinicopathological features of ILC tumors, discuss issues with clinical management, and highlight the disconnect between ILC biomarkers and patient outcomes. We review currently available data on ILC patient outcomes, with a focus on response to endocrine therapy. Additionally, we describe currently available laboratory models for understanding hormone response in ILC cells, and review current data on these model systems. The promise for new insight into ILC, based on extensive representation of the disease in recent large scale genomic studies, is also discussed. Increasing understanding of endocrine response in ILC represents a critical area for future research to improve patient outcomes for this understudied breast cancer subtype.
乳腺浸润性小叶癌(ILC)占所有新诊断乳腺癌的10%-15%,在美国每年影响约3万名女性。然而,ILC作为一种乳腺癌亚型的研究严重不足。尽管绝大多数ILC为雌激素受体阳性且具有总体良好的生物标志物,但与其他乳腺癌患者相比,ILC患者并未从改善的预后中获益。ILC患者的预后,尤其是对内分泌治疗的反应,目前尚不清楚,这在很大程度上是由于大型临床试验中缺乏前瞻性识别。此外,缺乏用于研究ILC细胞信号传导、激素反应和内分泌抵抗的实验室模型。在本综述中,我们概述了ILC肿瘤的临床病理特征,讨论了临床管理问题,并强调了ILC生物标志物与患者预后之间的脱节。我们回顾了目前关于ILC患者预后的可用数据,重点是对内分泌治疗的反应。此外,我们描述了目前用于理解ILC细胞激素反应的实验室模型,并回顾了这些模型系统的现有数据。基于近期大规模基因组研究中该疾病的广泛代表性,讨论了对ILC获得新见解的前景。增强对ILC内分泌反应的理解是未来研究的一个关键领域,以改善这种研究不足的乳腺癌亚型患者的预后。