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. Author manuscript; available in PMC: 2015 Oct 1.
Published in final edited form as: Menopause. 2014 Oct;21(10):1160–1164. doi: 10.1097/GME.0000000000000220

Figure 4.

Figure 4

Evolution of acquired SERM resistance. After long-term treatment with SERMs (1–2 years in vivo), initially responsive ER-positive tumors become resistant to treatment and are stimulated by SERMs (Phase I resistance) as well as by E2. After long-term transplantation into SERM-treated animal (5+years), breast tumor growth is inhibited by E2, though still stimulated by SERMs (Phase II of resistance). This process with SERMs in vivo is replicated with estrogen deprivation with MCF-7 breast cancer cells in vitro; cells initially start to grow spontaneously but estrogen still induces growth (hypersensitivity). This is Phase I. Long-term estrogen deprivation causes spontaneous growth in culture but apoptosis with physiologic estrogens both in vitro and in vivo (Phase II) (Jordan VC 2004 Cancer Cell 5:207–213 reproduced with permission ).