Abstract
Ki-S1, a marker of proliferation, and bcl-2, thegene product of which is an antagonist ofapoptosis, have been measured in 51 ER-positive primarybreast cancers before and during tamoxifen treatment andthen related to clinical response. Both markers weredetected in the majority of tumours before treatmentand, quantitatively, initial expression of Bcl-2 protein, butnot Ki-S1, was significantly related to the percentagereduction in tumour volume as assessed by ultrasound.
Staining for both markers was lower in posttreatment samples than in those taken prior totreatments, but concordant decreases in staining indices wereseen in only 11 of the 51 tumours.The results demonstrate, using clinical material, that theresponse to tamoxifen may involve changes in proliferationand/or susceptibility to cell-death.
Similar content being viewed by others
References
McGuire WL, Carbone PP, Sears ME: Estrogen Receptors in Human Breast Cancer: An Overview. Raven Press, New York, 1995, pp 1–7
Low SC, Dixon AR, Bell J, Ellis IO, Elston CW, Robertson JFR, Blamey RW: Tumour oestrogen receptor content allows selection of elderly patients with breast cancer for conservative tamoxifen treatment. Br J Surg 79: 1314–1316, 1992
Furr BJ, Jordan VC: The pharmacology and clinical uses of tamoxifen. Pharmacol Ther 25: 127–205, 1984
Forrest APM, Anderson EDC, Gaskill D: Primary systemic therapy for breast cancer. Br Med Bull 47: 357–371, 1991
Horobin JM, Preece PE, Dewar JA, Wood RA, Cuschieri A: Long-term follow-up of elderly patients with locoregional breast cancer treated with tamoxifen only. Br J Surg 78: 213–217, 1991
Forrest APM, Levack PA, Chetty U, Hawkins RA, Miller WR, Smyth JF, Anderson TJ: A human tumour model. Lancet 2: 840–842, 1986
Kreipe H, Heidebrecht HJ, Hansen S, Rohlk W, Kubbies M, Wacker HH, Tiemann M, Radzun HJ, Parwaresch R: A new proliferation-associated nuclear antigen detectable in paraffin-embedded tissues by the monoclonal antibody Ki-S1. Am J Pathol 142: 3–9, 1993
Hockenbery D, Dunez G, Milliman C, Schreiber RD, Korsmeyer SJ: bcl-2 Is an inner mitochondrial membrane protein that blocks programmed cell death. Nature (Lond.) 348: 334–336, 1990
Miyashita T, Reed JC: bcl-2 Gene transfer increases relative resistance of S49.1 and WEHI7.2 lymphoid cells to cell death and DNA fragmentation induced by glucocorticoids and multiple chemotherapeutic drugs. Cancer Res 52: 5407–5411, 1992
Lu Q-L, Poulsom R, Wong L, Hanby AM: bcl-2 Expression in adult and embryonic non-haematopoietic tissues. J Pathol 169: 431–437, 1993
Hockenbery D, Zutter M, Hickey W, Nahm M, Korsmeyer SJ: Bcl-2 protein is topographically restricted in tissues characterised by apoptotic cell death. Proc Natl Acad Sci USA 88: 6961–6965, 1991
Colombel M, Symmans F, Gil S, O'Toole KM, Chopin D, Benson M, Olson CA, Korsmeyer S, Buttyan R: Detection of the apoptosis-suppressing oncoprotein bcl-2 in hormone-refractory human prostate cancers. Am J Pathol 143: 390–400, 1993
Hsu SM, Raine L, Fanger H: Use of avidin-biotin peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabelled antibody (PAP) procedures. J Histochem Cytochem 29: 577–580, 1981
Shi S-R, Key ME, Kalra KL: Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem 39: 741–748, 1991
EBCTCG (Early Breast Cancer Trialists' Collaborative Group): Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy: 133 randomised trials involving 31000 recurrences and 24000 deaths among 75000 women. Lancet 339: 1–15, 71–85, 1992
Powles TJ, Hardy JR, Ashley SE, Farrington GM, Cosgrove D, Davey JB, Dowsett M, McKinna JA, Nash AG, Sinnett HD, Tillyer CR, Treleaven JG: A pilot trial to evaluate the acute toxicology and feasibility of tamoxifen for prevention of breast cancer. Br J Cancer 60: 126–131, 1989
Anderson EDC, Forrest APM, Hawkins RA, Anderson TJ, Leonard RCF, Chetty U: Primary systemic therapy for operable breast cancer. Br J Cancer 63: 561–566, 1991
Gaskell DJ, Hawkins RA, de Carteret S, Chetty U, Sangster K, Forrest APM: Indications for primary tamoxifen therapy in elderly women with breast cancer. Br J Surg 79: 1317–1320, 1992
Sutherland RL, Green MD, Hall RE, Reddel RR, Taylor IW: Tamoxifen induces accumulation of MCF-7 human mammary carcinoma cells in the G0/G1 phase of the cell cycle. Eur J Cancer Clin Oncol 19: 615–621, 1983
Ferguson DJP, Anderson TJ: Ultrastructural observations on cell death by apoptosis in the ‘resting’ human breast. Virchows Arch 393: 193–203, 1981
Warri AM, Huovinen RL, Laine AM, Martikainen PM, Harkonen PL: Apoptosis in toremifene-induced growth inhibition of human breast cancer cells in vivo and in vitro. J Natl Cancer Inst 85: 1412–1418, 1993
Aaltomaa S, Lipponen P, Syrjanen K: Prognostic value of cell proliferation in breast cancer as determined by proliferating cell nuclear antigen (PCNA) immunostaining. Anticancer Res 12: 1281–1286, 1992
Nicholson RI, McClelland RA, Finlay P, Eaton CL, Gullick WJ, Dixon AR, Robertson JF, Ellis IO, Blamey RW: Relationship between EGF-R, c-erB B-2 protein expression and Ki67 immunostaining in breast cancer and hormone sensitivity. Eur J Cancer 29A: 1018–1023, 1993
Leek RD, Kaklamanis L, Pezzella F, Gatter KC, Harris AL: bcl-2 in normal human breast and carcinoma, association with oestrogen receptor-positive, epidermal growth factor receptor-negative tumours and in situ cancer. Br J Cancer 69: 135–139, 1994
Nathan B, Gusterson B, Jadayel D, O'Hare M, Anbazhagan R, Jayatilake H, Ebbs S, Micklem K, Price K, Gelber R: Expression of BCL-2 in primary breast cancer and its correlation with tumour phenotype. Ann Oncol 5: 409–411, 1994
Johnston SRD, MacLennan KA, Sacks NPM, Salter J, Smith IE, Dowsett M: Modulation of Bcl-2 and Ki-67 expression in oestrogen receptor-positive human breast cancer by tamoxifen. Eur J Cancer 30A: 1663–1669, 1994
Chan WK, Poulsom R, Lu Q-L, Patel K, Gregory W, Fisher CJ, Hanby AM: bcl-2 Expression in invasive mammary carcinoma: correlation with apoptosis, hormone receptors and p53 expression (Abstract). J Pathol 169: 153A, 1993
Paradiso A, Lorusso S, Tommasi F, Schittulli F, Maiello E, De Lena M: Relevance of cell kinetics to hormonal response of receptor-positive advanced breast cancer. Breast Cancer Res Treat 11: 31–36, 1988
Amadori D, Volpi A, Callea A, Amaducci L, Morgagni S, Magni E, Nanni O: Clinical relevance of cell kinetics in breast cancer. Ann NY Acad Sci 698: 186–192, 1993
Gee JMW, Robertson JFR, Ellis IAO, Willsher P, McClelland RA, Hoyle HB, Kyme SR, Finlay P, Blamey RW, Nicolson RI: Immunocytochemical localization of Bcl-2 protein in human breast cancers and its relationship to a series of prognostic markers and response to endocrine therapy. Int J Cancer 59: 619–628, 1994
Clarke RB, Laidlaw LJ, Jones LJ, Howell A, Anderson E: Effect of tamoxifen on Ki67 labeling index in human breast tumours and its relationship to estrogen and progesterone receptor status. Br J Cancer 67: 606–611, 1993
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Keen, J., Dixon, J., Miller, E. et al. The expression of Ki-S1 and BCL-2 and the response to primary tamoxifen therapy in elderly patients with breast cancer. Breast Cancer Res Treat 44, 123–133 (1997). https://doi.org/10.1023/A:1005796915388
Issue Date:
DOI: https://doi.org/10.1023/A:1005796915388