Timing of breast cancer surgery during the luteal menstrual phase may improve prognosis

A meta-analysis has been performed of available retrospective reports concerning the 5-15 year disease-free survival of 5,353 premenopausal breast cancer patients operated on either during the follicular or luteal phases of the menstrual cycle. Patients with surgery performed during the luteal phase (d 14-23+) had an overall mean 5% benefit compared to those operated on the follicular phase determined by date of onset of their last menstrual period p = 0.02 by Wilcoxon 2-tailed test. When nodal invasion was reported, node-negative patients had a 5 +/- 2% SEM benefit. Patients with positive nodes had a 34 +/- 3% SEM increase in survival (p = .05), including both estrogen and progesterone-receptor negative as well as positive neoplasms. In 3 of 4 reports from major cancer treatment centers, each containing 249-1175 cases, risk of recurrent cancer and/or death increased 5 to 6-fold after 10 years for women receiving surgery during d 7-14 of their cycle, compared to those resected during d 21-36. Improvement in prognosis was greatest for patients with the highest risk of recurrence due to node-invasive disease and receptor dysfunction. Several cell-mediated immunologic factors inimical to metastasis are maximal in the luteal phase of the menstrual cycle, including natural killer cell activity. A new drug which augments natural killer cell activity may extend any beneficial survival results to post-menopausal breast cancer patients in the future. We conclude that accurate menstrual histories should be included in the medical record from now on for all premenopausal women receiving any surgical procedure upon the breast, preferably using an objective method of determining the date of last ovulation. Prospective randomized clinical trials are necessary to determine the full extent of survival benefits of late luteal surgical timing.