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Concentrations of oestrone and 4‐hydroxyandrostenedione in malignant and normal breast tissues
Author(s) -
Reed M. J.,
Aherne G. W.,
Ghilchik M. W.,
Patel S.,
Chakraborty J.
Publication year - 1991
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910490415
Subject(s) - androstenedione , endocrinology , estrone , medicine , breast cancer , chemistry , aromatase , mammary gland , breast tissue , estrogen , hormone , cancer , androgen
4‐Hydroxyandrostenedione (4‐OHA) is a specific inhibitor of aromatase activity used for the treatment of breast cancer in post‐menopausal women. Treatment with 4‐OHA has been shown to inhibit the peripheral conversion of androstenedione to oestrone and reduce plasma oestrogen concentrations, but the effect of treatment on breast‐tissue oestrone concentrations is not known. We have therefore examined the effect of treatment with 4‐OHA on oestrone concentrations in normal and malignant breast tissues and also measured plasma and tissue 4‐OHA concentrations. Changes in tumour oestrone concentrations were related to DNA polymerase α activity, a marker of cellular proliferation. Blood and breast‐tissue samples were obtained before and 36 hr after treatment with 4‐OHA. The mean plasma concentration of 4‐OHA was 27.9 ± 19.3 ng/ml, compared with levels of 33.7 ± 25.6 ng/g for breast tumour and 13.5 ± 11.5 ng/g for normal breast tissue. There was a significant correlation between 4‐OHA concentrations in plasma and normal breast tissue (r = 0.91, p < 0.001). Treatment with 4‐OHA resulted in a significant ( p < 0.02) decrease in breast‐tissue oestrone concentrations. For 3/4 tumour samples, a marked decrease in the concentration of oestrone (78 ± 4%) was associated with a similar decrease (64 ± 16%) in DNA polymerase α activity. It is concluded that treatment with 4‐OHA effectively reduces breast‐tissue exposure to oestrogen.