Abstract
We have investigated the effect of tamoxifen on the biological characteristics of the primary tumour in 33 patients with breast cancer. All patients had pre-treatment biopsy of the primary breast cancer and subsequent trucut biopsy of the primary tumour after 1–4 months on tamoxifen therapy.
The staining patterns in the primary tumour of each of the tumour antigens 115D8, DF3, NCRC-11, and carcinoembryonic antigen (CEA) were unaffected by tamoxifen therapy: there was 16%–31% change before vs. during tamoxifen therapy, but this did not reach significance for any of the four antigens. Comparison of the pattern of staining between the four antigens showed 115D8, DF3, and NCRC-11 to be similar to each other both before and during tamoxifen therapy. All three antigens were significantly different from the staining pattern shown by CEA before and during therapy.
Tumour antigen expression pre-treatment did not correlate with therapeutic response for any of the four antigens. However, NCRC-11 staining during tamoxifen therapy did correlate with response (p=0.004).
There was no significant difference in oestrogen receptor status before and during tamoxifen therapy, both of which correlated with response. DNA ploidy of the tumour before tamoxifen did not correlate with response to therapy, but there was a weak correlation between response and DNA ploidy measured during tamoxifen therapy.
In only a minority of tumours (up to 30%) did tamoxifen exert an effect on the biological characteristics studied. Changes in these biological markers were mainly in tumours which responded to tamoxifen, and the changes seen were a tendency to greater expression of differentiation antigens. It is uncertain whether these changes are a primary or a secondary effect of tamoxifen with respect to inducing tumour response.
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References
Willis JK, London DR, Ward HWC, Butt WR, Lynch SS, Budd BJ: Recurrent breast cancer treated with the anti-oestrogen tamoxifen; correlation between hormonal changes and clinical course. Br Med J 1: 425–428, 1977
Groom GU, Griffiths K: Effects of the antioestrogen tamoxifen on the plasma levels of luteinising hormone, follicle stimulating hormone, prolactin, oestradiol and progesterone in normal premenopausal women. J Endocrinol 70: 421–428, 1976
Raudin PM, Fritz NF, Twomey DC, Jordan VC: Endocrine status of premenopausal node-positive breast cancer patients following adjuvant chemotherapy and long-term tamoxifen. Cancer Res 48: 1026–1029, 1988
Farr BJA, Jordan VC: The pharmacology and clinical uses of tamoxifen: Pharmac Ther 25: 127–205, 1984
Blamey RW, Bishop HM, Blake JRS, Doyle PJ, Elston CW, Haybittle JC, Nicholson RI, Griffiths K: Relationship between primary breast tumour receptor status and patient survival. Cancer 46: 2765–2769, 1980
Campbell FC, Blamey RW, Elston CW, Morris AH, Nicholson RI, Griffiths K, Haybittle JL: Quantitative oestradiol receptor values in primary breast cancer and response of metastases to endocrine therapy. Lancet ii: 1317, 1981
Gaskell DJ, Hawkins RA, Sangster K, Chetty U, Forrest APM: Relation between immunocytochemical estimation of oestrogen receptor in elderly patients with primary breast cancer and response to tamoxifen. Lancet i: 1044–46, 1989
Howat JMT, Harris M, Swindell R, Barnes DM: The effect of oestrogen and progesterone receptors on recurrence and survival in patients with carcinoma of the breast. Br J Cancer 51: 263–270, 1985
Baildam AD, Zaloudik J, Howell A, Barnes DM, Turnbull L, Swindell R, Moore M, Sellwood RA: DNA analyses by flow cytometry, response to endocrine treatment and prognosis in advanced carcinoma of the breast. Br J Cancer 55: 553–559, 1987
Campbell FC, Blamey RW, Elston CW, Nicholson RI, Griffiths K, Haybittle JC: Oestrogen-receptor status and site of metastasis in breast cancer. Br J Cancer 44: 456, 1981
Knight WA, Livingston RB, Gregory EJ, Walder AC, McGuire WL: Estrogen receptor as an independent prognostic factor for early recurrence in breast cancer. Cancer Res 37: 4669–4671, 1977
Maynard PV, Blamey RW, Elston CW, Haybittle JL, Griffiths K: Estrogen receptor assay in primary breast cancer as an independent prognostic factor for early recurrence. Cancer Research 38: 4292–4295, 1978
Kallioniemi OP, Blanco G, Alavaikko M, Hietamen T, Mattila J, Lauslaliti K, Koivulo T: Tumour DNA ploidy as an independent prognostic factor in breast cancer. Br J Cancer 56: 637–642, 1987
Cornelisse CJ, Van-de-Velde CJ, Caspen RJ, Modenaar AJ, Hermans T: DNA ploidy and survival in breast cancer patients. Cytometry 8: 225–235, 1987
Hedley DW, Rugg CA, Gelber RD: Association of DNA index and S-phase fraction with prognosis of node positive early breast cancer. Cancer Res 47: 4729–4735, 1987
Klintenberg C, Stal O, Nordenskold B, Wallgren A, Arvidsson S, Skoog C: Aneuploid DNA content and high S-phase fraction of tumour cells are related to poor prognosis in patients with primary breast cancer. Eur J Cancer Clin Oncol 23: 277–282, 1987
Robertson JFR, Ellis IO, Bell J, Todd J, Robins RA, Elston CW, Blamey RW: Carcinoembryonic antigen immunocytochemistry in primary breast cancer. Cancer 64: 1638–1645, 1989
Ellis IO, Bell J, Todd JH, Williams M, Dowle C, Robins RA, Elston CW, Blamey RW, Baldwin RW: Evaluation of immunoreactivity with monoclonal antibody NCRC-11 in breast cancer. Br J Cancer 56: 295–299, 1987
Williams MR, Gilson D, Marsh L, Morgan DAL, Nicholson RI, Elston CW, Griffiths K, Blamey RW: The early results from a randomised study of radiotherapy versus Nolvadex (tamoxifen) as initial treatment for Stage III breast cancer. Eur J Surg Oncol 14: 235–240, 1988
Robertson JFR, Ellis IO, Todd JH, Elston CW, Blamey RW: A randomised study of mastectomy or tamoxifen for elderly patients with operable breast cancer. Br Med J 297: 511–514, 1988
Ellis IO, Robins RA, Elston CW, Blamey RW, Ferry B, Baldwin RW: A monoclonal antibody, NCRC-11, raised to human breast carcinoma: production and immunohistological characteristation. Histopathology 8: 501–506, 1984
Hilkens J, Buijs F, Hilgers J, Hagemann PH, Sennenberg A, Koldowski U, Karande K, van Hoeven RP, Feltkamp C, von de Rijn JM: Monoclonal antibodies to human milk fat globule membranes. In: Peeters H (ed) Protides of the Biological Fluids. Proceedings 29th Colloq. Pergamon, New York, 1981, pp 813–816
Hilkens J, Hilgers J, Buijs F, Hagemann PH, Schol D, Doorneward GV, van Tweed J: Monoclonal antibodies against human milk fat globule membranes useful in carcinoma research. In: Peeters H (ed) Protides of the Biological Fluids. Proceedings 31st Colloq. Pergamon, New York, 1983 pp. 1013–1016
Kufe DW, Inghirami G, Abe M, Hayes DF, Justi-Wheeler H, Schlom J: Differential reactivity of a novel monoclonal antibody (DF3) with human malignant versus benign breast tumours. Hybridoma 3: 223–232, 1984
Stenberger LA: Immunocytochemistry (2nd ed). John Wiley and Sons, New York, 1979
Hsu SM, Raine L, Fanger H: Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques. J Histochem Cytochem 29: 577–580, 1981
Robertson JFR: MD Thesis. University of Glasgow, 1989
Dowle CS, Owainati A, Robins A, Burns K, Ellis IO, Elston CW, Blamey RW: Prognostic significance of the DNA content of human breast cancer. Br J Surg 74: 133–136, 1987
Walker KJ, Bouzaber N, Robertson J,et al.: Immunocytochemical localisation of oestrogen receptor in human breast tissue: Cancer Res 48: 6517–6522, 1988
Hayward JL, Carbone PP, Heuson J-C, Kumaoko S, Segaloff A, Rubens RD: Assessment of response to therapy in advanced breast cancer. Cancer 39: 1289–1293, 1977
British Breast Group: Assessment of response to treatment in advanced breast cancer. Lancet ii: 38–39, 1974
Robertson JFR, Williams MR, Todd J, Nicholson RI, Morgan DAL, Blamey RW: Factors predicting the response of patients with advanced breast cancer to endocrine (Megace) therapy. Eur J Cancer Clin Oncol 25: 469–475, 1989
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Robertson, J.F.R., Ellis, I.O., Nicholson, R.I. et al. Cellular effects of tamoxifen in primary breast cancer. Breast Cancer Res Tr 20, 117–123 (1991). https://doi.org/10.1007/BF01834641
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DOI: https://doi.org/10.1007/BF01834641