Background: Many studies have addressed the effect of the timing of surgery for breast cancer relative to menstrual cycle phase, with
conflicting results. Explanations for the possibility that survival could be altered by the appropriate timing of breast cancer
surgery in humans remain speculative.
Methods: We examined the expression of three estrogen related proteins (c-
erbB-2, cathepsin D, pS2) in the breast tumors from 69 premenopausal women sampled in different phases of the menstrual cycle.
Data on S-phase fraction and hormone receptor expression were also analyzed. Immunohistochemical assays were used to measure
the proteins of interest. S-phase fraction was determined by flow cytometry. Analyses were performed based on fraction of
cells staining positive for the protein, density of stain, and a histoscore that combined both fraction of positive cells
and density.
Results: We found no differences in c-
erbB-2, cathepsin D, hormone receptor, or S-phase levels in tumors sampled in the follicular versus luteal phase, or perimenstrual
versus periovulatory phase. The exception was pS2, which was expressed at greater levels during the luteal than during the
follicular phase of the cycle (p<0.01); but there was no difference in pS2 expression when the patients were classified as
periovulatory versus perimenstrual.
Conclusions: Our findings do not support a variation in c-
erbB-2, cathepsin D, S-phase fraction, or receptor expression as an explanation for the differences in breast cancer prognosis
when surgery is timed by menstrual cycle phase. The finding that pS2 (an indicator of hormone sensitivity, and possibly better
prognosis) is expressed at higher levels in tumor samples during the luteal phase suggests that the biologic profile of breast
tumors may vary with the menstrual cycle and that these variations deserve further study.
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