Estrogen receptor status, adrenal androgens and 7 alpha-hydroxydehydroepiandrosterone in breast cancer patients.
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.
D000367:Age Factors; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000378:metabolism*; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000097:blood*; D019314:Dehydroepiandrosterone Sulfate; D005260:Female; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000378:metabolism*
D011960:Receptors, Estrogen; D003687:Dehydroepiandrosterone; C003587:7-hydroxydehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate