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Influence of aminoglutethimide on plasma oestrogen levels in breast cancer patients on 4-hydroxyandrostenedione treatment
Authors:P. E. Lønning  M. Dowsett  A. Jones  D. Ekse  S. Jacobs  F. McNeil  D. C. Johannessen  T. J. Powles
Affiliation:(1) Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway;(2) Department of Academic Biochemistry, The Royal Marsden Hospital, Fulham Road, SW3 6JJ London, UK;(3) Department of Medicine, The Royal Marsden Hospital, Surrey, UK
Abstract:Summary The clinical and biochemical effects of combined treatment with the two aromatase inhibitors aminoglutethimide and 4-hydroxyandrostenedione were evaluated in 10 patients suffering from advanced breast cancer. All patients had become resistant to treatment with one of the drugs before having combined treatment. Seven patients progressing on 4-hydroxyandrostenedione who had aminoglutethimide added to their treatment and achieved a further suppression of plasma oestradiol by a mean of 40.0% (p<0.05). Plasma oestrone was suppressed by a mean of 40.6% (p<0.025) and plasma oestrone sulphate was suppressed by a mean of 63.6% (p<0.025). Two of the patients, neither of whom had responded to 4-hydroxyandrostenedione alone, experienced objective tumour regression when aminoglutethimide was given in concert. Three patients progressing on aminoglutethimide who had 4-hydroxyandrostenedione added showed no further suppression of their plasma oestrogen levels, and no tumour regression was observed. These findings suggest a dose-response relationship between plasma oestrogen suppression at low postmenopausal levels and objective tumour response in breast cancer.
Keywords:aminoglutethimide  aromatase inhibition  breast cancer  4-hydroxyandrostenedione  oestrogen  oestrone sulphate
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