MENSTRUAL-CYCLE TIMING OF BREAST-CANCER R ESECTION - INFLUENCE ON THEPROGNOSIS

Purpose: The overall purpose of this exercise is to rigorously determi ne the relative strenght of the hypothesis that the menstrual cycle ti ming of operation has an impact on the outcome and to determine whethe r or not a specific change in the practice of breast surgical oncology can be recommended. Method: In 1989 preliminary results of a retrospe ctive study were published which identified the timing of breast cance r surgery in relation to the menstrual cycle as an independent predict or of disease-free survival. At least dozens of reports have subsequen tly appeared, some supporting and others refuting the claim. This is a critical review of the outcomes of 8632 women published since 1989 in 31 retrospective studies, relevant to the possibility that the timing of primary breast cancer resection within the menstrual cycle impacts on breast cancer recurrence and/or patient survival. This article con trasts the adequacy of information and data analysis presented in each publication. Therefore we constructed an objective score for evaluati ng the quality of data. This score consists of the most relevant param eters, necessary to clarify the problem. Results: 14 studies including 3236 patients have reported, that the time of breast cancer resection during the menstrual cycle has an impact on the outcome. 17 retrospec tive studies with 5396 patients cannot confirm an influence of surgery timing on the prognosis in premenopausal breast cancer patients. A co mparison of the quality of data among these studies demonstrates great variability. Arbitrary bisections of the menstrual cycle, the applica tion of vastly different primary and adjuvant treatment strategies, th e cumulative distribution (distribution function) of tumour stage of d isease at diagnosis, duration of follow-up and the methods and precisi on of data analysis all differ markedly. Eight high-quality studies ha ve been most completely reported. While two of these find no impact, s ix (75%) of these studies find that breast cancer outcome is affected by operative timing. The design of two ongoing prospective studies is considered inadequate. Conclusion: Although it is likely that the mens trual cycle phase of operation is relevant to outcome, the nature of t he available data does not permit a clear recommendation in respect of the timing of operation. Hence, it is concluded that current retrospe ctive data are insufficient to recommend an immediate change in practi ce. Prospective studies of this potentially important question are ess ential. The minimal requirements for adequate prospective study are ou tlined. Three elements seem to be essential, namely: the accurate tria ngulation of surgery within the cycle, temporal coordination of multip le surgical procedures if more than one operation is employed, and the investigation of menstrual cycle-coordinated biological functions pot entially relevant to breast cancer resection outcome.