Summary
Many studies have addressed the clinical value of pS2 as a marker of hormone responsiveness and of cathepsin D (Cath D) as a prognostic factor in breast cancer. Because pS2 and Cath D are both oestrogen induced in human breast cancer cell lines, we studied the influence of the menstrual cycle phase and menopausal status at the time of surgery on the levels of these proteins in breast cancer. A population of 1750 patients with breast cancer, including 339 women in menstrual cycle, was analysed. Tumoral Cath D and pS2 were measured by radioimmunoassay. Serum oestradiol (E2), progesterone (Pg), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels at the day of surgery were used to define the hormonal phase in premenopausal women. There was a trend towards a higher mean pS2 level in the follicular phase compared with the luteal phase (17 ng mg–1and 11 ng mg–1respectively, P= 0.09). Mean pS2 was lower in menopausal patients than in women with cycle (8 ng mg–1and 14 ng mg–1respectively, P= 0.0001). No differences in mean Cath D level were observed between the different phases of the menstrual cycle, or between pre- and post-menopausal women. In the overall population, pS2 was slightly positively associated with E2 and Pg levels and negatively associated with FSH and LH, probably reflecting the link between pS2 and menopausal status. In premenopausal women, no association was found between pS2 and E2, Pg, FSH or LH levels. There were no correlations between Cath D level and circulating hormone levels in the overall population. However, in the subgroup of premenopausal women with ER-positive (ER+) tumours, E2 was slightly associated with both pS2 and Cath D, consistent with oestrogen induction of these proteins in ER+ breast cancer cell lines. There are changes in pS2 level in breast cancer throughout the menstrual cycle and menopause. This suggests that the choice of the pS2 cut-off level should take the hormonal status at the time of surgery into account. In contrast, the level of Cath D is unrelated to the menstrual cycle and menopausal status.
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References
Badwe, R. A., Gregory, W. M., Chaudary, M. A., Richards, M. A., Bentley, A. E., Rubens, R. D. & Fentiman, I. S. (1991). Timing of surgery during menstrual cycle and survival of premenopausal women with operable breast cancer. Lancet 337: 1261–1264.
Badwe, R. A., Bettelheim, R., Millis, R. R., Gregory, W., Richards, M. A. & Fentiman, I. S. (1995). Cyclical tumour variations in premenopausal women with early breast cancer. Eur J Cancer 13: 2181–2184.
Cazin, J. L., Gosselin, P., Boniface, B. & Demaille, A. (1993). Expression of PS2 and cathepsin D in breast cancer. Int J Oncol 2: 1081–1084.
Clark, G. M. & McGuire, W. L. (1988). Steroid receptors and other prognostic factors in primary breast cancer. Semin Oncol 15: 20–25.
Coradini, D., Cappelleti, V., Miodini, P., Ronchi, E., Scavone, G. & Di Fronzo, G. (1984). Variations in estrogen and progesterone receptor content in premenopausal breast cancer patients throughout the menstrual cycle. Tumori 70: 339–344.
Fentiman, I. S., Gregory, W. M. & Richards, M. A. (1994). Effect of menstrual phase on surgical treatment of breast cancer. Lancet 344: 402
Ferrandina, G., Scambia, G., Benedetti Panici, P., Mancuso, S. & Messori, A. (1997). Relationship between cathepsin D content and disease-free survival in node-negative breast cancer patients: a meta-analysis. Br J Cancer 76: 661–666.
Foekens, J. A., Rio, M. C., Seguin, P., Van Putten, W. L. J., Fauque, J., Nap, M., Klijn, J. G. M. & Chambon, P. (1990). Prediction of relapse and survival in breast cancer patients by pS2 protein status. Cancer Res 50: 3832–3837.
Gion, M., Mione, R., Dittadi, R., Romanelli, M., Capitanio, G., Friede, U., Barbazza, R., Visona, A. & Dante, S. (1995). Relationship between cathepsin D and other pathological and biological parameters in 1752 patients with primary breast cancer. Eur J Cancer 31A: 671–677.
Granata, G., Coradini, D., Cappeletti, V. & Difronzo, G. (1991). Prognostic relevance of cathepsin D vs oestrogen receptors in node-negative breast cancer. Eur J Cancer 27: 970–972.
Henry, J. A., Nicholson, S., Hannesy, C., Lennard, T., May, F. & Westley, B. (1989). Expression of the oestrogen related pNR-2 mRNA in human breast cancer: relation to oestrogen receptor mRNA levels and response to tamoxifen therapy. Br J Cancer 63: 32–38.
Holdaway, I. M., Mason, B. H., Lethaby, A. E., Harman, J. E., France, J. T. & Knox, B. S. (1997). Characteristics of the menstrual cycle at the time of surgery for breast cancer. Br J Cancer 75: 413–416.
Holli, K., Isola, J. & Hakama, M. (1995). Prognostic effect of timing of operation in relation to menstrual phase of breast cancer patient – fact or fallacy. Br J Cancer 71: 124–127.
Khan, S. A., Gonchoroff, N. J. & Miller, L. E. (1997). Expression of pS2, c-erbB-2, and cathepsin D during the menstrual cycle in human breast cancers. Ann Surg Oncol 4: 462–469.
Korenman, S. G. (1969). Comparative binding of estrogens and its relation to estrogenic potency. Steroids 13: 163–178.
Lowry, O. H., Roseborough, N., Farr, L. & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275.
Masiakowski, P., Breathnach, R., Bloch, J., Gannon, F., Krust, A. & Chambon, P. (1982). Cloning of cDNA sequences of hormone-related genes from the MCF-7 human breast cancer cell line. Nucleic Acids Res 10: 7895–7903.
Maudelonde, T., Escot, C., Pujol, P., Rouanet, P., Defrenne, A., Brouillet, J. P. & Rochefort, H. (1994). In vivo stimulation by tamoxifen of cathepsin D mRNA level in breast cancer. Eur J Cancer 30A: 2049–2053.
Mohr, P. E., Wang, D. Y., Gregory, W. M., Richards, M. A. & Fentiman, I. S. (1996). Serum progesterone and prognosis in operable breast cancer. Br J Cancer 73: 1552–1555.
Oliver, D. J. & Ingram, D. M. (1995). Timing of surgery during the menstrual cycle for breast cancer: possible role of growth factors. Eur J Cancer 3: 325–328.
Osborne, C. K., Yochmowitz, M. G., Knight, W. A. & McGuire, W. L. (1980). The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer 36: 2884–2888.
Pink, J. J. & Jordan, V. C. (1996). Models of estrogen receptor regulation by estrogens and antiestrogens in breast cancer cell lines. Cancer Res 56: 2321–2330.
Powles, T. J., Ashley, S. E., Nash, A. G., Tidy, A., Gazet, J. C. & Ford, H. T. (1991). Menstrual surgical timing (letter). Lancet 337: 1604
Predine, J., Spyratos, F., Prud’homme, J. F., Andrieu, C., Hacene, K., Brunet, M., Pallud, C. & Milgrom, E. (1992). Enzyme-linked immunosorbent assay of pS2 in breast cancers benign tumors, and normal breast tissues. Cancer 69: 2116–2123.
Pujol, P., Maudelonde, T., Daures, J. P., Rouanet, P., Brouillet, J. P., Pujol, H. & Rochefort, H. (1993). A prospective study of the prognostic value of cathepsin D levels in breast cancer cytosol. Cancer 71: 2006–2012.
Pujol, P., Daures, J. P., Thezenas, S., Guilleux, F., Rouanet, P. & Grenier, J. (1998). Changing estrogen and progesterone receptor patterns in breast cancer during the menstrual cycle and menopause. Cancer 83: 698–705.
Rageth, J. C., Wyss, P., Unger, C. & Hochuli, E. (1991). Timing of breast cancer surgery within the menstrual cycle: influence on lymph-node involvement, receptor status, postoperative metastatic spread and local recurrence. Ann Oncol 2: 269–272.
Rochefort, H. (1992). Biological and clinical significance of cathepsin D in breast cancer. Acta Oncol 31: 125–130.
Saad, Z., Bramwell, V. H. C., Wilson, S. M., O’Malley, F. P., Jeacock, J. & Chambers, A. F. (1998). Expression of genes that contribute to proliferative and metastatic ability in breast cancer resected during various menstrual phases. Lancet 351: 1170–1173.
Schwartz, L., Koerner, F., Edgerton, S. M., Sawicka, J. M., Rio, M. C., Bellocq, J. P., Chambon, P. & Thor, D. (1991). pS2 expression and response to hormonal therapy in patients with advanced breast cancer. Cancer Res 51: 624–628.
Senie, R. T., Rosen, P. P., Rhodes, P. & Lesser, M. L. (1991). Timing of breast cancer excision during the menstrual cycle influences the duration of disease-free survival. Ann Intern Med 115: 337–342.
Spyratos, F., Andrieu, C., Hacene, K., Chambon, P. & Rio, M. C. (1994). pS2 and response to adjuvant hormone therapy in primary breast cancer. Br J Cancer 69: 394–397.
Tandon, A. K., Clark, G. M., Chamness, G. C., Chirgwin, J. M. & McGuire, W. L. (1990). Cathepsin D and prognosis in breast cancer. N Engl J Med 322: 297–302.
Veronesi, U., Luini, A., Mariani, L., Del Vecchio, M., Alvez, D., Andreoli, C., Giacobone, A., Merson, M., Pacetti, G., Raselli, R. & Saccozzi, R. (1994). Effect of menstrual phase on surgical treatment of breast cancer. Lancet 343: 1544–1546.
Westley, B. R. & Rochefort, H. (1980). A secreted glycoprotein induced by estrogen in human breast cancer cell line. Cell 20: 352–362.
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Pujol, P., Daurès, JP., Brouillet, JP. et al. Time at surgery during menstrual cycle and menopause affects pS2 but not cathepsin D levels in breast cancer. Br J Cancer 79, 909–914 (1999). https://doi.org/10.1038/sj.bjc.6690145
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DOI: https://doi.org/10.1038/sj.bjc.6690145
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