Estrous cycle-dependent tumor cell proliferation during the estrous stage in MMTV-PyMT tumors. Credit: Nature (2024). DOI: 10.1038/s41586-024-08276-1
The Dutch Cancer Institute found that the stage of the estrous cycle significantly influences the sensitivity of breast tumors to chemotherapy. In mouse models of breast cancer, treatment initiated at the diestrus stage resulted in a reduced response to chemotherapy compared to initiation at the estrus stage.
The human body contains internal clocks to adapt to environmental changes, including infrared rhythms such as the menstrual cycle. Fluctuating hormonal levels during these cycles regulate physiological adaptations, which can impact responses to therapies.
Understanding the factors that contribute to heterogeneity in responses to chemotherapy is crucial to improving breast cancer treatment outcomes.
In the study “Estrous cycle stage affects sensitivity of breast tumors to chemotherapy,” published in NatureResearchers studied how different stages of the estrous cycle influence the effectiveness of neoadjuvant chemotherapy (NAC) in the treatment of breast cancer.
NAC responses varied significantly depending on whether treatment was initiated during the diestrus or estrus stages of the cycle, suggesting that the timing of chemotherapy relative to menstrual or estrous cycles may optimize therapeutic outcomes in the treatment of breast cancer.
Using three mouse models and a retrospective analysis of human clinical data, they demonstrated systemic and localized changes during diestrus, such as an increase in chemoresistant mesenchymal cells, a reduction in vascular diameter, and an elevated presence of macrophages.
The decrease in tumor vessel diameter suggests potential constraints to drug delivery. A high presence of macrophages, previously associated with the induction of chemoresistance, was also noted during the diestrus phase.
Although NAC disrupts the estrous cycle, the high prevalence of macrophages persists. Macrophage depletion attenuated the reduced therapeutic response observed when treatment was initiated during diestrus.
The results suggest that the estrous cycle is a crucial factor in determining chemosensitivity, and that future clinical studies could exploit the optimal timing of treatment initiation to improve chemotherapy outcomes.
More information:
Laura Bornes et al, The stage of the estrous cycle affects the sensitivity of breast tumors to chemotherapy, Nature (2024). DOI: 10.1038/s41586-024-08276-1
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