Fertility Cycle Influence on Surgical Breast Cancer Cure

Abstract

Cancer growth and spread is an intricate process dependent upon both tumor and host. This laboratory is interested in the role of the fertility cycle, specifically cyclic changes in steroid hormone levels, in tumor growth and metastases. Our previous studies, using a murine model, have documented that breast cancer growth rate and post-resection metastatic behavior each change reproducibly during the estrous cycle, and that post-resection cancer spread depends upon the time within the estrous cycle that an advanced transplanted cancer is resected. Twelve to thiry-two percent cure rates were seen in these studies. That early work described estrous cycle stages just prior and near to putative ovulation to be superior while those stages farther from ovulation were disadvantageous times for surgery. Data presented here confirm the role of the estrous cycle in post-resection metastatic spread. This current work validates vaginal smear determined estrous cycle stage with uterine weight. A primary, transplantable, mammary carcinoma, which metastasizes to the lungs, was resected for surgical cure in cycling C₃HeB/FeJ female mice at each fertility cycle stage. A group of oophorectomized (ovx) animals was also used. In two large, independent studies resecting much earlier stage cancers than in prior studies, a 96% surgical cure frequency was documented when the tumor is resected during estrus. The second best surgical cure rate is achieved when tumors are resected during metestrus (79% overall cure rate). Cure frequency in ovx animals is intermediate. These results further support a probable role for circulating E₂ and P₄ levels in modulating the metastatic process. We conclude that the timing of surgical resection within the estrous cycle affects the cancer's metastatic potential and that the optimal timing of resection may also depend to some extent upon the size (stage) of the resected cancer.