Modifications of the first dihydronapthalene SERM, nafoxidine (see figure 10) that was a clinical candidate for the treatment of breast cancer but had side effects including severe phototoxicity, resulted in lasofoxifene ((5R,6S)-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro-naphthalen-2-ol; see figure 11). Nafoxidine has all three phenyls constrained in a coplanar arrangement like tamoxifen. But with hydrogenation, the double bond of nafoxidene were reduced, and both phenyls are cis-oriented. The amine-bearing side chain can then adopt an axial conformation and locate this group orthogonally to the plane of the core, like ralofoxifene and other less uterotropic SERMs.