Estrous rhythm found crucial for optimizing breast cancer therapy

The Netherlands Cancer Institute has found that the estrous cycle stage significantly influences mammary tumors’ sensitivity to chemotherapy. In mouse models of breast cancer, treatment initiated during the diestrus stage resulted in reduced responses to chemotherapy compared to initiation during the estrus stage.

The human body contains internal timekeeping clocks to adapt to environmental changes, including infradian rhythms like the menstrual cycle. Fluctuating hormone levels during these cycles regulate physiological adaptations, which may impact responses to therapies.

Understanding factors that contribute to the heterogeneity in chemotherapy responses is crucial for improving treatment outcomes in breast cancer.

In the study, “The oestrous cycle stage affects mammary tumor sensitivity to chemotherapy,” published in Nature, the researchers investigated how different stages of the estrous cycle influence the effectiveness of neoadjuvant chemotherapy (NAC) in treating 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 in relation to menstrual or estrous cycles could optimize therapeutic outcomes in breast cancer treatment.

Using three mouse models and retrospective human clinical data analysis, they demonstrated systemic and localized changes during diestrus, such as increased chemoresistant mesenchymal cells, reduced vascular diameter, and elevated macrophage presence.

Decreased tumor vessel diameter suggests potential constraints to drug delivery. Elevated presence of macrophages, previously associated with inducing chemoresistance, was also noted during the diestrus phase.

While NAC disrupts the estrous cycle, the elevated macrophage prevalence persists. Depleting macrophages mitigated the reduced therapy response observed when initiating treatment during diestrus.

The findings suggest that the estrous cycle is a crucial factor in determining chemosensitivity, and future clinical studies may exploit optimal treatment initiation timing for enhanced chemotherapy outcomes.

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