A new study has identified a set of genes that may be responsible for previous reports that cancer recurrence after surgery to remove breast cancer is less likely if the surgery is performed during the luteal phase (after ovulation) of the menstrual cycle than if the operation is performed during the follicular phase (before ovulation). Variations in gene expression associated with the menstrual cycle may be one explanation for the fact that cancer recurrence and death occur more often and sooner among premenopausal than postmenopausal women with breast cancer. The authors performed whole mouse genome microarrays on mammary tumors resected during pre-ovulatory (diestrus, follicular) and post-ovulatory (estrus, luteal) phases of the estrous cycle. These tumors had known post-surgical cure or relapse (pulmonary metastasis) outcomes. This allowed the authors to identify a set of genes whose expressions are modulated based on fertility cycle, and which may be associated with prognosis. Identified were 90 genes in mammary tumors whose expressions change meaningfully (up to 100-fold) in accordance with the estrous cycle, 69 genes that are associated with cure/relapse independently of estrous cycle stage at resection, and 24 genes that change (up to 12-fold) across the estrous cycle and are also associated with disease outcome. The authors conclude that the genetic pathways identified in this study are potential targets for the development of therapies which may serve to delay or prevent relapse by preventing dormant micrometastatic tumor cells from escaping their dormant state post-operatively.

Relationship between timing of surgery and prognosis remains controversial

The idea that survival of premenopausal patients is influenced by the menstrual cycle phase in which breast cancer surgery is performed started to be explored in the early 1990s. Inconsistent findings and the apparent lack of a convincing scientific basis for the hypothesis eventually reduced the level of interest in the topic. The present study could revive interest in altering the patient hormonal status shortly before and after surgery for breast cancer in order to improve long-term outcome for premenopausal women.