Atashgaran Vahid, Wrin Joseph, Barry Simon Charles, Dasari Pallave, Ingman Wendy V
Discipline of Surgery, School of Medicine, The Queen Elizabeth Hospital, University of Adelaide, Adelaide, SA, Australia; The Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia.
The Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia; Molecular Immunology Laboratory, Discipline of Pediatrics, University of Adelaide, North Adelaide, SA, Australia.
Front Oncol. 2016 Dec 26;6:267. doi: 10.3389/fonc.2016.00267. eCollection 2016.
Fluctuations in circulating estrogen and progesterone across the menstrual cycle lead to increased breast cancer susceptibility in women; however, the biological basis for this increased risk is not well understood. Estrogen and progesterone have important roles in normal mammary gland development, where they direct dynamic interactions among the hormonally regulated mammary epithelial, stromal, and immune cell compartments. The continuous fluctuations of estrogen and progesterone over a woman's reproductive lifetime affect the turnover of mammary epithelium, stem cells, and the extracellular matrix, as well as regulate the phenotype and function of mammary stromal and immune cells, including macrophages and regulatory T cells. Collectively, these events may result in genome instability, increase the chance of random genetic mutations, dampen immune surveillance, and promote tolerance in the mammary gland, and thereby increase the risk of breast cancer initiation. This article reviews the current status of our understanding of the molecular and the cellular changes that occur in the mammary gland across the menstrual cycle and how continuous menstrual cycling may increase breast cancer susceptibility in women.
月经周期中循环雌激素和孕激素的波动会导致女性患乳腺癌的易感性增加；然而，这种风险增加的生物学基础尚未得到充分理解。雌激素和孕激素在正常乳腺发育中具有重要作用，它们指导激素调节的乳腺上皮、基质和免疫细胞区室之间的动态相互作用。女性一生中雌激素和孕激素的持续波动会影响乳腺上皮、干细胞和细胞外基质的更新，还会调节乳腺基质和免疫细胞（包括巨噬细胞和调节性T细胞）的表型和功能。总体而言，这些事件可能导致基因组不稳定，增加随机基因突变的机会，削弱免疫监视，并促进乳腺中的耐受性，从而增加患乳腺癌的风险。本文综述了我们目前对月经周期中乳腺发生的分子和细胞变化的理解现状，以及持续的月经周期如何增加女性患乳腺癌的易感性。
