Researchers from the VIB-KU Leuven Center for Cancer Biology, the Netherlands Cancer Institute, Oncode Institute, and the University of Cambridge have unveiled a connection between the menstrual cycle and the dissemination of mutant cells in breast tissue. Published in Nature, the study reveals how the natural growth and subsequent regression of milk ducts during the menstrual cycle can promote the spread of these mutant cells, potentially leading to tumor development.
While breast tissue in healthy individuals may appear normal, it can harbor extensive areas of mutant cells capable of evolving into cancerous tumors. The greater the number of these mutant cells within a seemingly healthy tissue, the higher the likelihood that one will exhibit abnormal behavior and lead to cancer. However, the mechanisms behind the emergence of these expansive fields of mutant cells have remained largely unclear.
Some researchers suggest that the spread of mutant cells across large tissue areas may significantly contribute to the initiation and recurrence of breast cancer. The international team, led by Professors Colinda Scheele, Jacco van Rheenen, and Benjamin Simons, has presented new evidence indicating that the normal remodeling of breast tissue during the menstrual cycle may inadvertently drive breast cancer development.
During the menstrual cycle, mouse mammary glands undergo extensive remodeling. Elevated estrogen levels stimulate the formation of small alveoli, which can develop into milk-producing units during pregnancy. In the absence of pregnancy, the body recognizes these structures as unnecessary and initiates their breakdown at the end of the cycle, effectively removing most of the expanded cells.
While this process is generally effective at eliminating excess cells—including mutant ones—it is not foolproof. Some mutant cells may survive the cleanup, and the remodeling process can inadvertently facilitate their proliferation within healthy tissue. This dual nature of tissue remodeling presents a paradox: it aids in the removal of excess cells while simultaneously allowing for the expansion of a few surviving mutant cells.
In their study, the researchers tracked the evolution of labeled healthy and mutant stem cells in the mammary tissue of mice over several months. Their observations indicated that the menstrual cycle significantly influenced the behavior of these cells, enabling some to spread over considerable distances.
Professor Colinda Scheele noted, “Our findings show that the menstrual cycle influences the behavior of labeled cells, allowing some to spread over large distances.” Jacco van Rheenen added, “With each menstrual cycle, there is a slight chance that mutated clones can expand and spread throughout the breast tissue. This suggests that an increased number of cycles raises the likelihood of this occurrence, potentially explaining why pregnancies and breastfeeding are associated with a reduced risk of breast cancer.”
While this research enhances our understanding of the early stages of tumor formation, further studies are required to identify potential interventions that could prevent mutated cells from developing into cancer. The research team plans to investigate human tissue samples to confirm whether similar mechanisms operate in the human body.
This research was supported by the Cancer Grand Challenges PRECISION team, along with funding from the Boehringer Ingelheim Foundation, the FEBS Excellence Award, the Fonds Wetenschappelijk Onderzoek, EMBO, and the European Research Council.
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