Dall Genevieve, Risbridger Gail, Britt Kara
Metastasis Research Laboratory, Peter MacCallum Cancer Centre, 7 St Andrews Place, East Melbourne 3002, Australia; Department of Anatomy and Developmental Biology, Monash University Clayton, Wellington Rd 3800, Australia.
Department of Anatomy and Developmental Biology, Monash University Clayton, Wellington Rd 3800, Australia.
J Steroid Biochem Mol Biol. 2017 Jun;170:54-60. doi: 10.1016/j.jsbmb.2016.02.018. Epub 2016 Feb 22.
Parity (childbearing) significantly decreases a woman's risk of breast cancer and the protective effect is greater if the woman is younger and has more children. The mechanism/s of parity-induced protection are not known. Although several factors are postulated to play a role, we discuss how a reduction in the number of mammary stem cells (MaSCs) may lead to a reduction in breast cancer risk in parous women. Firstly we review the epidemiology linking childbearing to reduced breast cancer risk and discuss how additional births, a young age at first full term birth, and breastfeeding impact the protection. We then detail the mouse and human studies implicating MaSC in parity induced protection and the in-vivo work being performed in mice to directly investigate the effect of parity on MaSC. Finally we discuss the transplant and lineage tracing experiments assessing MaSC activity according to parity and the need to define if MaSC are indeed more carcinogen sensitive than mature mammary epithelial cells. Continuing and future studies attempting to define the parity induced mechanisms will aid in the development of preventative therapies.
生育次数（分娩情况）会显著降低女性患乳腺癌的风险，而且如果女性更年轻且生育子女更多，这种保护作用会更强。生育诱导保护的机制尚不清楚。尽管推测有几个因素发挥作用，但我们将讨论乳腺干细胞（MaSCs）数量的减少如何可能导致经产妇患乳腺癌风险的降低。首先，我们回顾将生育与降低乳腺癌风险联系起来的流行病学，并讨论额外生育、首次足月分娩时的年轻年龄以及母乳喂养如何影响这种保护作用。然后，我们详细介绍涉及MaSC在生育诱导保护中的小鼠和人体研究，以及正在小鼠体内进行的直接研究生育对MaSC影响的工作。最后，我们讨论根据生育情况评估MaSC活性的移植和谱系追踪实验，以及确定MaSC是否确实比成熟乳腺上皮细胞对致癌物更敏感的必要性。持续的和未来试图确定生育诱导机制的研究将有助于预防性治疗的发展。
