EXPRESSION OF PS2, C-ERBB-2, AND CATHEPSIN-D DURING THE MENSTRUAL-CYCLE IN HUMAN BREAST CANCERS

Background: Many studies have addressed the effect of the timing of su rgery for breast cancer relative to menstrual cycle phase, with confli cting 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 estro gen related proteins (c-erbB-2, cathepsin D, pS2) in the breast tumors from 69 premenopausal women sampled in different phases of the menstr ual cycle. Data on S-phase fraction and hormone receptor expression we re also analyzed. Immunohistochemical assays were used to measure the proteins of interest. S-phase fraction was determined by flow cytometr y. Analyses were performed based on fraction of cells staining positiv e for the protein, density of stain, and a histoscore that combined bo th Fraction of positive cells and density. Results: We found no differ ences in c-erbB-2, cathepsin D, hormone receptor, or S-phase levels in tumors sampled in the follicular versus luteal phase, or perimenstrua l versus periovulatory phase. The exception was pS2, which was express ed at greater levels during the luteal than during the follicular phas e of the cycle (p < 0.01); but there was no difference in pS2 expressi on when the patients were classified as periovulatory versus perimenst rual. Conclusions: Our findings do not support a variation in c-erbB-2 , cathepsin D, S-phase fraction, or receptor expression as an explanat ion for the differences in breast cancer prognosis when surgery is tim ed by menstrual cycle phase. The finding that pS2 (an indicator of hor mone sensitivity, and possibly better prognosis) is expressed at highe r levels in tumor samples during the luteal phase suggests that the bi ologic profile of breast tumors may vary with the menstrual cycle and that these variations deserve further study.