Dey Pranay, Brisken Cathrin
ISREC-Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Division of Breast Cancer Research, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, United Kingdom.
Cancer Res. 2025 Mar 14;85(6):1013-1014. doi: 10.1158/0008-5472.CAN-25-0335.
A recent publication by Bornes and colleagues explored the impact of the estrous cycle on mammary tumor response to neoadjuvant chemotherapy. Using genetically engineered mouse models, Bornes and colleagues revealed that chemotherapy is less effective when initiated during the diestrous stage compared with during the estrous stage. A number of changes during diestrus were identified that may reduce chemosensitivity of mammary tumors: an increased mesenchymal state of breast cancer cells during diestrus, decreased blood vessel diameters, and higher numbers of macrophages in the tumor microenvironment. Macrophage depletion was sufficient to mitigate this resistance. To translate these findings to humans, retrospective analyses of premenopausal patients with breast cancer were conducted. Serum progesterone levels served to determine the menstrual cycle phases, which revealed that treatment efficacy is reduced in women receiving neoadjuvant chemotherapy during the luteal (progesterone-high) phase compared with those treated during the follicular (progesterone-low) phase. The findings show that physiologic hormone fluctuations may influence chemosensitivity through tumor cell-extrinsic mechanisms, with the important implication that aligning treatment initiation with the menstrual cycle improves therapeutic outcomes and that consideration of systemic factors may improve therapy outcomes.
博恩斯及其同事最近发表的一篇论文探讨了发情周期对乳腺肿瘤新辅助化疗反应的影响。通过基因工程小鼠模型，博恩斯及其同事发现，与发情期相比，在动情后期开始化疗效果较差。研究确定了动情期的一些变化，这些变化可能会降低乳腺肿瘤的化疗敏感性：动情期乳腺癌细胞的间充质状态增加、血管直径减小以及肿瘤微环境中巨噬细胞数量增多。巨噬细胞耗竭足以减轻这种耐药性。为了将这些发现应用于人类，对绝经前乳腺癌患者进行了回顾性分析。血清孕酮水平用于确定月经周期阶段，结果显示，与在卵泡期（孕酮水平低）接受新辅助化疗的女性相比，在黄体期（孕酮水平高）接受新辅助化疗的女性治疗效果较差。这些发现表明，生理激素波动可能通过肿瘤细胞外在机制影响化疗敏感性，这具有重要意义，即使治疗开始时间与月经周期同步可改善治疗效果，并且考虑全身因素可能会改善治疗结果。
