Timing of surgery for primary breast cancer with regard to the menstrual phase and prognosis

The hormonal milieu of the patient at the time of surgery may influence the prognosis of patients with primary breast cancer. Circulating unopposed estrogen is perhaps detrimental, while circulating progesterone may confer a survival advantage. This hypothesis has particular relevance to the timing of surgery in relation to the menstrual cycle. After all, the first 14 days of the menstrual cycle (follicular phase) are characterized by high levels of circulating unopposed estrogen, while circulating progesterone is present during the second 14 days of the cycle (luteal phase). Several retrospective studies have shown that surgery during the follicular phase of the menstrual cycle results in a worse disease-free and overall survival. Randomized controlled trials addressing the effect of timing of surgery or neoadjuvant hormonal therapy on breast cancer mortality are urgently needed to confirm or refute the unopposed estrogen hypothesis. Such trials may provide important insights into the natural history of breast cancer, and a basis for significantly reducing breast cancer mortality.