Plasma concentrations of
dehydroepiandrosterone (DHA), DHA-sulphate (
DHAS) and 7 alpha hydroxy-DHA (7 alpha OHDHA) were measured and compared with
tumor estrogen receptor (ER) status in 33 postmenopausal patients with
breast cancer. Although the plasma concentrations of DHA,
DHAS and 7 alpha OHDHA were not different between the ER-positive (ER+) and ER-negative (ER-) patient groups, the ratios of 7 alpha OHDHA/
DHAS and of DHA/
DHAS were significantly higher (P less than 0.001 and P less than 0.001 respectively) in the ER- group. Nine women (normal or with benign
breast disease) of similar age and menopausal status had values for plasma 7 alpha OHDHA/
DHAS and DHA/
DHAS between those of ER+ and ER- patient groups. The measurement of these
steroid ratios in the plasma of
breast cancer patients thus provides an indirect estimate of ER status. Since DHA and 7 alpha OHDHA are major metabolites of precursor
DHAS in mammary
tumor tissues, changes in their relative quantities in plasma may reflect the influence of receptor-mediated events on mammary
steroid metabolism. Alternatively, the relative increase in
tumor metabolism of
androgens inferred from high 7 alpha OHDHA/
DHAS and DHA/
DHAS ratios in the ER- group may disrupt the hormonal microenvironment of the
estrogen receptor. These events may, in turn, predispose toward ER status and a poor response to endocrine
therapy.