Timing of surgery for premenopausal women with breast cancer

Breast cancer is one of the most common causes of mortality and morbidity and the majority of women diagnosed with breast cancer undergo treatment which includes surgical intervention, radiotherapy or chemotherapy, or both. This review attempted to ascertain if the timing of tumour removal in relation to different stages of the menstrual cycle has an impact on overall survival or disease-free survival in premenopausal breast cancer patients. The follicular stage of the menstrual cycle relates to days 0 to 14, prior to ovulation. The luteal phase relates to days 15 to 35, after ovulation. If small changes in the timing of surgery could predictably improve the survival rates, any inconvenience and complexity is a small price to pay for the benefit. There were no completed randomised controlled trials comparing surgery performed during the follicular phase and the luteal phase of the menstrual cycle. We identified one ongoing randomised multicentre study and three prospective observational studies.

Of the three prospective observational studies, one reported no survival differences between menstrual cycle groups after stratification by lymph node status at a mean follow-up of 48 months. The results showed a lack of prognostic value (recurrence-free survival and overall survival) of timing of surgery in relation to the menstrual period or to oestrogen and progesterone levels in premenopausal breast carcinoma patients. One study gave no data on mean survival time or recurrence-free survival and the third study reported no significant difference in the overall survival of patients when surgery was done in either the follicular or luteal phase of the menstrual cycle.

A large randomised controlled trial would be ideal to establish the influence of timing of surgery in relation to the menstrual cycle (follicular phase or luteal phase) on the prognosis of breast cancer. However, in the absence of this, the information available from the prospective observational studies shows that there is no difference in disease-free survival and overall survival in non-metastatic breast cancer patients irrespective of whether the surgery was done during the follicular or the luteal phase.

Authors' conclusions: 

In the absence of RCTs, this review provides evidence from large prospective observational studies that timing of surgery does not show a significant effect on survival.

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Background: 

The majority of women diagnosed with breast cancer undergo a multidisciplinary treatment with surgical intervention and radiotherapy or chemotherapy, or both. The importance of timing of tumour removal in relation to the menstrual cycle and its influence on disease-free survival and overall survival has been studied by researchers since 1989 but still remains speculative.

Objectives: 

To determine if surgery performed either during the follicular or luteal phase of the menstrual cycle affects the overall and disease-free survival of premenopausal breast cancer patients.

Search strategy: 

We searched the Cochrane Breast Cancer Group Trials Register (January 2009), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 1), MEDLINE (1966 to January 2009), EMBASE (1974 to September 2006) and the WHO International Clinical Trials Registry Platform (ICTRP) search portal (July 2010). We checked references of articles and communicated with authors.

Selection criteria: 

Randomised controlled trials (RCTs) comparing breast surgery during the follicular phase of the menstrual cycle with the luteal phase in premenopausal women. Prospective non-RCTs or observational studies were considered if randomised studies were lacking.

Data collection and analysis: 

Three authors independently extracted data and assessed trial quality.

Main results: 

Completed randomised trials were not found. There is one trial that is currently ongoing in Italy; the results have yet to be published.

Two prospective observational studies had data on recurrence-free survival. One study reported an odds ratio for recurrence rate at one year (where > 1 favours the luteal phase) of 0.86 (95% confidence interval (CI) 0.69 to 1.08); 0.87 at two years (95% CI 0.69 to 1.09); 0.95 at three years (95% CI 0.75 to 1.21); 1.12 at four years (95% CI 0.87 to 1.43); and 1.12 at five years (95% CI 0.87 to 1.43). Another study reported a hazard ratio for overall survival of 1.02 (95% CI 0.995 to 1.04, P = 0.14) and for disease-free survival of 1.00 (95% CI 0.98 to 1.02, P = 0.92) at three years based on the last and first menstrual period. The results were not significant. There was no difference in the recurrence rate whether the surgery was done during the follicular or luteal phase of the menstrual cycle.

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