Hormonally regulated proteins in breast secretions ave markers of target organ sensitivity

Anti-oestrogen therapy is being used in an attempt to prevent breast cancer but no intermediate end points of the effect of tamoxifen on the normal br east are available. Therefore, the purpose of this study was to develop a p hysiological measure of oestrogen action on the breast. We measured oestrog en-stimulated and -inhibited proteins in breast secretions from women on an d off anti-oestrogen therapy. Two oestrogen-stimulated proteins (pS2 and ca thepsin D) and oestrogen-inhibited proteins (CP15, gross cystic disease flu id protein 15; Apo,: apolipoprotein D) were measured. Premenopausal women h ad significantly higher pS2 and cathepsin D in association with lower Apo D and CP15 secretion levels compared to post-menopausal women. Sequential ni pple aspirates from women treated with the luteinizing hormone releasing ho rmone agonist goserelin (n = 9), tamoxifen (n = 9) and hormone replacement therapy (HRT) (n = 26) were measured. Following treatment with goserelin, m edian nipple secretion levels of pS2 fell (P < 0.02) and Apo D and CP15 ros e significantly (P < 0.03 and P < 0.05 respectively). Similar changes were seen on tamoxifen therapy but not in untreated control women. Treatment wit h HRT resulted in a rise of pS2 (P < 0.001) and a fall in Apo D (P < 0.05). Measurement of pS2 and Apo D in nipple aspirates may prove useful intermed iate end point of breast responsiveness to anti-oestrogens. (C) 2000 Cancer Research Campaign.