title: Dissecting the Biology of Menstrual Cycle-Associated Breast Cancer Risk.
abstract: 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.
authors.affiliation: 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.
authors.forename: Vahid
authors.initials: V
authors.lastname: Atashgaran
authors.affiliation: 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.
authors.forename: Joseph
authors.initials: J
authors.lastname: Wrin
authors.affiliation: The Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia; Molecular Immunology Laboratory, Discipline of Pediatrics, University of Adelaide, North Adelaide, SA, Australia.
authors.forename: Simon Charles
authors.initials: SC
authors.lastname: Barry
authors.affiliation: 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.
authors.forename: Pallave
authors.initials: P
authors.lastname: Dasari
authors.affiliation: 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.
authors.forename: Wendy V
authors.initials: WV
authors.lastname: Ingman
keywords: cytokine; estrogen; menstrual cycle; microenvironment; progesterone