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The Women's Health Initiative study confirmed that hormone therapy (HT) raises risk for breast cancer. However, this was true only with combined therapy: Estrogen alone (in women with hysterectomies) did not raise risk (JW Gen Med Apr 25 2006). This information incriminated progestins as a factor in breast cancer — a plausible theory, given that mammary epithelial cells have progesterone receptors as well as estrogen receptors.
Two research groups report that, in mice, progestins stimulate production of a molecule called RANKL, which in turn induces proliferation of mammary epithelial cells. RANKL stimulates growth of osteoclasts, so its activity in breast tissue was a surprise. A pharmacological inhibitor of RANKL lowered the incidence and …