Could NSAIDs become a preventative therapy in pregnancy-associated breast cancer?
Could NSAIDs become a preventative therapy in pregnancy-associated breast cancer?
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DOI：
10.2217/bmt.12.15
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发表时间：
2012-05-01
影响因子：
0.7
通讯作者：
Schedin, Pepper
中科院分区：
文献类型：
--
作者：
Borges, Virginia F.;Schedin, Pepper
妊娠相关性乳腺癌（PABC）是一种独特类型的年轻女性乳腺癌，包括两种生物学上不同的疾病：妊娠期间诊断的疾病和产后诊断的疾病。它是产后PABC的主要子集，与较高的乳腺癌死亡率更一致。临床前工作已经确定产后退化的正常事件是富含免疫细胞的伤口愈合环境。我们已经表明，退化环境驱动肿瘤生长，增殖和转移。此外，我们已经在动物模型中证明，这种“退化效应”可以用药物治疗消除，即NSAID，其靶向与PABC肿瘤促进有关的正常退化途径。从这个角度来看，我们回顾了当代对PABC的理解，我们的临床前建模及其影响，以及未来将这些临床前研究转化为合理和安全的人体临床试验所需的未满足的研究需求。
Pregnancy-associated breast cancer (PABC) is a unique type of young women's breast cancer that includes two biologically distinct conditions: those diagnosed during pregnancy and those diagnosed postpartum. It is the dominant subset of postpartum PABC that is more consistently associated with higher breast cancer mortality. Preclinical work has identified the normal event of postpartum involution as a wound-healing milieu rich in immune cells. We have shown that the involution environment drives tumor growth, proliferation and metastasis. Moreover, we have demonstrated in animal models that this 'involution effect' can be abrogated with drug therapy, namely NSAIDs, which target normal involution pathways implicated in PABC tumor promotion. In this perspective, we review the contemporary understanding of PABC, our preclinical modeling and its implications and the unmet research needs required for future translation of these preclinical studies into rational and safe human clinical trials.