In situ oestrone synthesis in normal breast and breast tumour tissues: effect of treatment with 4-hydroxyandrostenedione.

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. 3H-Androstenedione and 14C-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 3H-androstenedione, 3H-oestrone derived from 3H-androstenedione and 14C-oestrone were isolated and measured. DNA polymerase alpha 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 3H-oestrone from 3H-androstenedione accounted for the major part (84.3 +/- 9.0%) of the 3H-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 3H-androstenedione or 14C-oestrone into breast tissues, in situ formation of 3H-oestrone was only detected in one tumour sample after treatment. DNA polymerase alpha activity decreased in 4/6 tumours after treatment with 4-hydroxyandrostenedione. Overall, however, there was no significant correlation between the level of 3H-oestrone formed in situ and DNA polymerase alpha 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.