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in situ oestrone synthesis in normal breast and breast tumour tissues: Effect of treatment with 4‐hydroxyandrostenedione
Author(s) -
Reed M. J.,
Owen A. M.,
Lai L. C.,
Coldham N. G.,
Ghilchik M. W.,
Shaikh N. A.,
James V. H. T.
Publication year - 1989
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.2910440208
Subject(s) - androstenedione , in situ , estrone , breast cancer , aromatase , medicine , endocrinology , chemistry , hormone , cancer , androgen , organic chemistry
An isotopic infusion technique has been used in an attempt to determine the contribution that local, in situ , oestrone synthesis makes to the oestrogen content of breast tumours. 3 H‐Androstenedione and 14 C‐oestrone were infused into women with advanced breast cancer for 12 hr before operation. At surgery, normal breast and breast tumour biopsy samples were obtained and 3 H‐androstenedione, 3 H‐oestrone derived from 3 H‐androstenedione and 14 C‐oestrone were isolated and measured. DNA polymerase α activity, a marker of cellular proliferation, was also measured to examine whether local synthesis of oestrone exerted a biological effect. The study was repeated after patients had been treated with the aromatase inhibitor, 4‐hydroxyandrostenedione, before undergoing further surgery for removal of their tumours. In 4/6 tumours examined, in situ synthesis of 3 H‐oestrone from 3 H‐androstenedione accounted for the major part (84.3 ± 9.0%) of the 3 H‐oestrone detected, while no significant in situ synthesis occurred in 2 other tumours. Although treatment with 4‐hydroxyandrostenedione did not significantly alter the uptake of 3 H‐androstenedione or 14 C‐oestrone into breast tissues, in situ formation of 3 H‐oestrone was only detected in one tumour sample after treatment. DNA polymerase α activity decreased in 4/6 tumours after treatment with 4‐hydroxyandrostenedione. Overall, however, there was no significant correlation between the level of 3 H‐oestrone formed in situ and DNA polymerase α activity (r = 0.38, NS). It is concluded that in some, but not all, breast tumours in situ formation of oestrone can make an important contribution to the oestrogen content of breast tumours.