in preclinical models, fulvestrant has been
shown to have high efficacy in a low-estrogen
environment.6 The combination of fulvestrant and
an aromatase inhibitor, as compared with either
agent alone, delays the development of resistance
by down-regulating several signaling molecules
involved in the development of resistance.7,8 We
therefore conducted a phase 3, randomized trial
to determine whether the combination of anastrozole
and fulvestrant would be superior to anastrozole
alone as first-line therapy for metastatic
breast cancer.