Fig. 10.

A proposed clinical strategy for the optimal application of third-line antihormonal therapy. We propose that patients who have initially responded to, and then failed, two previous antihormonal therapies may exhibit Phase II antihormonal resistance, and would then benefit from short-term low-dose estrogen, which would induce apoptosis in the Phase II resistant cells and debulk the tumor. Prior laboratory evidence indicates that the small percentage of Phase II tumors which revert to an estrogen-stimulated stage after estrogen-induced regression, are also re-sensitized to antihormonal therapy [47, 49]. A low tumor burden would be maintained by FUL in an estrogen-depleted environment, i.e. FUL plus an aromatase inhibitor, to avoid the possible emergence of tumor growth through a negative interaction between FUL and physiologic estrogen.