Short Communications. Steroid metabolism by human breast tumours

Extensive studies relating urinary 11-deoxy-17oxo steroids and prognosis in patients with advanced breast carcinoma (Bulbrook, 1965) have directed attention to the maj or source of urinary Cl9 steroids, DHA* sulphate, which is secreted by the adrenal and is present in plasma in high concentration (Yamaji & Ibayashi, 1969). Its metabolism by extra-adrenal tissue is therefore of particular interest. Adams & Wong (1968a, 1969) demonstrated in breast tumour tissue the presence of steroidmetabolizing enzymes capable of converting cholesterol into pregnenolone, 1 7c-hydroxyprogesterone into androstenedione (androst-4-ene-3, 1 7-dione) and testosterone into oestriol [oestra-1,3,5(10)-triene3,16a, 1 7fl-triol]. This communication now presents results from studies similar to those of Adams & Wong (1968a), together with preliminary data from the perfusion of [7oe-3H]DHA sulphate through human breast tumours in situ. Important differences, however, were found in the nature of some of the metabolites isolated, which bear fundamentally on the concept of hormone action in the breast. Tuinour tissue was maintained at 0°C after removal from the patient until prepared for incubation 30min later. The tissue was thinly sliced, the slices were chopped into smaller segments with a razor blade and portions were incubated with radioactive steroids (Table 1) in Krebs-Ringer bicarbonate-glucose medium (Cohen, (1957) (12.5 ml/g of tissuLe), shaking at 37°C in an atmosphere of 02 +CO2 (95: 5) for 2h without addition of cofactors. Purity of incubated precursors was checked by isotope-dilution analysis before incubation. Reactions were stopped by addition of acetone, and known quantities in the range 300-500,ug each of the non-radioactive carrier steroids, shown in Table 1, added in ethanol. Mixtures were homogenized in a Silverson mixer and separated into neutral, phenolic and conjugated fractions as described by Fahmy, Griffiths, Turnbull & Symington (1968). Perfusion studies were performed on tumours localized in the medial half of the breast, supplied