AI Article Synopsis
- The oestrous cycle significantly affects breast cancer's response to neoadjuvant chemotherapy (NAC), with treatment during the dioestrus stage resulting in less effectiveness compared to the oestrus stage.
- In mouse models and human premenopausal cohorts, dioestrus is associated with increased chemoresistance, characterized by more cells undergoing epithelial-to-mesenchymal transition, narrower tumor blood vessels, and higher macrophage levels.
- Understanding the impact of the oestrous cycle on treatment response could lead to improved timing for chemotherapy, enhancing patient outcomes.
Article Abstract
The response of breast cancer to neoadjuvant chemotherapy (NAC) varies substantially, even when tumours belong to the same molecular or histological subtype. Here we identify the oestrous cycle as an important contributor to this heterogeneity. In three mouse models of breast cancer, we show reduced responses to NAC when treatment is initiated during the dioestrus stage, when compared with initiation during the oestrus stage. Similar findings were observed in retrospective premenopausal cohorts of human patients. Mechanistically, the dioestrus stage exhibits systemic and localized changes, including (1) an increased number of cells undergoing epithelial-to-mesenchymal transition linked to chemoresistance and (2) decreased tumour vessel diameter, suggesting potential constraints to drug sensitivity and delivery. In addition, an elevated presence of macrophages, previously associated with chemoresistance induction, characterizes the dioestrus phase. Whereas NAC disrupts the oestrous cycle, this elevated macrophage prevalence persists and depletion of macrophages mitigates the reduced therapy response observed when initiating treatment during dioestrus. Our data collectively demonstrate the oestrous cycle as a crucial infradian rhythm determining chemosensitivity, warranting future clinical studies to exploit optimal treatment initiation timing for enhanced chemotherapy outcomes.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666466 | PMC |
| http://dx.doi.org/10.1038/s41586-024-08276-1 | DOI Listing |
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