Hormonally-regulated proteins in breast secretions are 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 breast are available. Therefore, the purpose of this study was to develop a physiological measure of oestrogen action on the breast. We measured oestrogen-stimulated and -inhibited proteins in breast secretions from women on and off anti-oestrogen therapy. Two oestrogen-stimulated proteins (pS2 and cathepsin D) and oestrogen-inhibited proteins (CP15, gross cystic disease fluid protein 15; Apo ,: apolipoprotein D) were measured. Premenopausal women had significantly higher pS2 and cathepsin D in association with lower Apo D and CP15 secretion levels compared to post-menopausal women. Sequential nipple aspirates from women treated with the luteinizing hormone releasing hormone agonist goserelin (n = 9), tamoxifen (n = 9) and hormone replacement therapy (HRT) (n = 26) were measured. Following treatment with goserelin, median nipple secretion levels of pS2 fell (P< 0.02) and Apo D and CP15 rose significantly (P< 0.03 and P< 0.05 respectively). Similar changes were seen on tamoxifen therapy but not in untreated control women. Treatment with 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 intermediate end point of breast responsiveness to anti-oestrogens. © 2000 Cancer Research Campaign