Selective estrogen receptor modulators (SEAMs) Tamoxifen citrate Though chemically related to clomiphene, it has complex actions; acts as potent estrogen antagonist in breast carcinoma cells, blood vessels and at some peripheral sites, but as paial agonist in uterus, bone, liver and pituitary. Inhibition of human breast cancer cells, and hot flushes reflect antiestro.e;enic action while the weak estrogen agonistic action manifests as stimulation of endometrial proliferation,lowering of Gn and prolactin levels postmenopausal women as well as improvement in their bone density. Tamoxifen is the standard hormonal treatment of breast cancer in both pre- and post menopausal women, though aromatase inhibitors are gaining prominence. In early cases it is given as postmastectomy adjuvant therapy, while in advanced cases it is a constituent of palliative .treatment. Response rates are high in ER-positive breast carcinomas, but some ER-negative tumours also respond suggesting additional nonhormonal mechanism of action. It is also effective following surgery in cancer of male breast. Based on large epidemiological studies which have shown 45% reduction in the incidence of ER positive breast cancer, it has been approved for primary prophylaxis of breast cancer in high risk women. Recurrence rate in ipsilateral as well as contralateral breasts is reduced by tamoxifen,but benefits of prophylactic therapy beyond 5 years are not proven; outcomes may even be worse. Improvement in bone mass due to antiresorptive effect, and in lipid profile are the other benefits of tamoxifen therapy. ESSENTIALS OF MEDICAL PHARMACOLOGY K.D.TRIPATHI SIXTH EDITION PAGE NO:304