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The biology and physiology of ‘Nolvadex’ (tamoxifen) in the treatment of breast cancer

  • Scandinavian Breast Cancer Symposium
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Summary

After more than a quarter of a million patient years experience with tamoxifen in the clinic, it is perhaps appropriate to re-examine the working hypothesis for the activity of this drug. This hypothesis states that tamoxifen is an anti-oestrogen which exerts its anti-tumour activity by competing for and binding to cytoplasmic oestrogen receptor protein in the tumour.

The evidence that tamoxifen is an anti-oestrogen in animals and man is seen to vary from species to species and between target organs within a species. The balance of the evidence supports the conclusion that this drug acts as an oestrogen antagonist in man.

If the activity of this drug were confined to an effect mediated by the oestrogen receptor (ER), there should be a clear correlation between the anti-tumour effect of tamoxifen and the presence of ER. The clinical and pre-clinical data are reviewed. Whilst the majority of the evidence points to an effect in advanced breast cancer mediated through the ER, there are data that show the correlation is not absolute. The data are examined and the evidence for non-receptor mediated anti-tumour activity is reviewed.

We conclude that whilst the majority of the activity of tamoxifen is that of an anti-oestrogen mediated through the ER, compelling evidence exists that this may not be its only anti-tumour activity at normal clinical doses. These findings might explain tamoxifen's activity in some ER negative tumours.

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Authors and Affiliations

  1. Clinical Research, Mereside, Alderley Park, SK10 4TG, Macclesfield, Cheshire, UK

    John Patterson M.B.

  2. Bioscience I, Mereside, Alderley Park, SK10 4TG, Macclesfield, Cheshire, UK

    Barry Furr Ph.D. & Alan Wakeling Ph.D.

  3. Departments of Imperial Chemical Industries PLC, Mereside, Alderley Park, SK10 4TG, Macclesfield, Cheshire, UK

    Linda Battersby M.A. (Medical)

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Patterson, J., Furr, B., Wakeling, A. et al. The biology and physiology of ‘Nolvadex’ (tamoxifen) in the treatment of breast cancer. Breast Cancer Res Tr 2, 363–374 (1982). https://doi.org/10.1007/BF01805878

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