Department of Anatomical Pathology, Tohoku University School of Graduate Medicine, Japan.
J Steroid Biochem Mol Biol. 2013 Jan;133:66-76. doi: 10.1016/j.jsbmb.2012.08.007. Epub 2012 Sep 5.
The clinical management of triple negative breast cancer (TNBC) is challenging due to the relatively aggressive biological behaviour and paucity of specific targeted therapy. A subset of TNBC patients has been reported to express androgen receptor (AR) in carcinoma cells and the manipulation of androgen signalling or AR targeted therapies have been proposed. However, the biological significance of AR in TNBC has remained relatively unknown. Therefore, this review aims to summarise the reported studies assessing the rates of AR positivity in TNBC patients and androgenic effects in TNBC cell lines. The rates of AR positivity among TNBC cases varied depending on the study population (0-53% of all TNBC patients). This difference among the reported studies may be largely due to the methodological differences of analysing AR. While the majority of cell line studies suggest that androgen increase proliferation and preliminary clinical studies suggest that AR antagonists improve the prognosis of AR positive TNBC patients, cell line transfection experiments and survival analyses of histological samples suggest that the presence of AR in tumour is either benign or predicts better survival. Therefore further translational investigations regarding the mechanisms of androgen action in TNBC are required to explain this discrepancy between clinical and basic studies.
由于三阴性乳腺癌(TNBC)具有相对侵袭性的生物学行为和缺乏特异性靶向治疗,其临床管理具有挑战性。据报道,TNBC 患者中有一部分表达癌细 胞中的雄激素受体(AR),并提出了操纵雄激素信号或 AR 靶向治疗的方法。然而,AR 在 TNBC 中的生物学意义仍然知之甚少。因此,本综述旨在总结评估 TNBC 患者 AR 阳性率和 TNBC 细胞系中雄激素作用的报道研究。TNBC 病例中 AR 阳性率因研究人群而异(所有 TNBC 患者的 0-53%)。这些报道研究之间的差异可能主要归因于分析 AR 的方法学差异。虽然大多数细胞系研究表明雄激素增加增殖,初步临床研究表明 AR 拮抗剂改善 AR 阳性 TNBC 患者的预后,但细胞系转染实验和组织学样本的生存分析表明,肿瘤中 AR 的存在是良性的,或预测更好的生存。因此,需要进一步进行关于雄激素在 TNBC 中作用机制的转化研究,以解释临床和基础研究之间的这种差异。