PURPOSE: To compare the effect of therapy with anastrozole versus a combination 
of fulvestrant and anastrozole in women in first relapse of endocrine-responsive 
breast cancer.
PATIENTS AND METHODS: Postmenopausal women, or premenopausal women receiving a 
gonadotropin-releasing hormone agonist, with estrogen receptor- and/or 
progesterone receptor-positive disease at first relapse after primary treatment 
of localized disease were open-label randomly assigned to a fulvestrant loading 
dose (LD) regimen followed by monthly injection plus 1 mg of anastrozole daily 
or to 1 mg of anastrozole daily alone. The primary end point was time to 
progression (TTP).
RESULTS: In all, 514 women were randomly assigned to fulvestrant plus 
anastrozole (experimental arm; n = 258) or anastrozole (standard arm; n = 256). 
Approximately two thirds had received adjuvant antiestrogens, but only eight 
individuals had received an aromatase inhibitor. Median TTP was 10.8 and 10.2 
months in the experimental versus standard arm, respectively (hazard ratio [HR] 
= 0.99; 95% CI, 0.81 to 1.20; P = .91); median overall survival was 37.8 and 
38.2 months, respectively (HR = 1.0; 95% CI, 0.76 to 1.32; P = 1.00). Incidences 
of prespecified adverse events (AEs) were similar. Hot flashes were more common 
in the experimental arm: 63 patients (24.6%) versus 35 patients (13.8%) in the 
standard arm (P = .0023). Death owing to AEs was reported in 11 (4.3%) and five 
patients (2.0%) in the experimental versus standard arm, respectively.
CONCLUSION: Fulvestrant (250 mg + LD regimen) in combination with anastrozole 
offered no clinical efficacy advantage over anastrozole monotherapy in this 
population of individuals with a relatively high proportion of previous adjuvant 
antiestrogen exposure.