Timing of breast cancer surgery in relation to the menstrual cycle phase - no effect on 3-year prognosis. The Yorkshire Breast Cancer Group Intervention, Timing and Survival Study.
Authors: Richard Sainsbury, Timothy J. Perren, Sarah R. Brown, Vicky L. Morrell, Mitch Dowsett, Helen C. Thorpe
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

484 

Background: The effect of timing of breast cancer surgery during the menstrual cycle on subsequent prognosis remains controversial. We conducted a multi-centre prospective observational study to establish whether timing of interventions within the menstrual cycle influences prognosis. Here we report results of 3-year overall survival (OS) and disease-free survival (DFS) for ‘primary analysis’ patients (regular cycles, no oral contraceptives within last six months). Methods: Data were collected regarding the timing of interventions (first tumor handling and subsequent surgeries) in relation to patients’ last menstrual period (LMP) and first menstrual period after intervention (FMP). Hormone profiles (follicle stimulating hormone, luteinizing hormone, oestradiol, progesterone) were also measured at each intervention. Cox’s Proportional Hazards model was used to assess the effect of menstrual cycle timing on OS and DFS adjusting for type of intervention, Nottingham Prognostic Index and adjuvant treatments. Initial analysis incorporated LMP into the Cox model in its continuous form and subsequent exploratory analyses used the categorizations of Senie, Badwe and Hrushesky. Hormone profiles were also used to define patients’ menstrual cycle phase. Results: 611 patients were recruited from 25 centers between 1993 and 2000. Median age was 43 (range 19-55) years. At a median follow-up of 58 (range 0-132) months there have been 115 deaths; 56 occurred within 3 years of surgery. Types of initial surgery were excision biopsy (18%), lumpectomy (48%) and mastectomy (33%). 14% of tumors were grade I, 42% grade II, 40% grade III; 51% were node positive. Menstrual cycle according to LMP was not statistically significant at the 5% level for the 412 patients in the ‘primary analysis’ group (OS hazard ratio (HR) =1.02, 95% confidence interval (CI) (0.995, 1.042), p=0.14; DFS HR=1.00, 95% CI (0.980, 1.022), p=0.92). Exploratory analyses according to the categorizations of Senie, Badwe and using hormone profiles indicated possible increased OS in patients whose intervention occurred during the follicular phase of the menstrual cycle. Discussion: In this analysis timing of surgery in relation to the menstrual cycle phase had no significant impact on survival at 3 years. This may be explained by our lower than expected event rate or problems with reliably identifying patients’ exact menstrual cycle phase. However survival curves up to 10 years indicate results remain true for longer term survival. Unlike previous studies this cohort has received modern adjuvant treatments, some of which will have caused ovarian suppression. Further analysis will accurately determine menstrual cycle phase by using hormone profiles with LMP and FMP data. Full results of all 3-year analyses will be released at this meeting.