In the overall population, between-group differences in efficacy end points favored tamoxifen, and statistical noninferiority of fulvestrant could not be demonstrated. However, in patients with hormone receptor-positive tumors, fulvestrant had similar efficacy to tamoxifen and was well tolerated.

Previous studies suggest that disease recurrence peaks at around 2 years in patients with early stage breast cancer (EBC), but provide no data regarding recurrence type. This retrospective analysis aimed to identify early recurrence types and risk factors in estrogen receptor-positive (ER?) EBC patients treated with adjuvant tamoxifen following breast cancer surgery. Postmenopausal women diagnosed with ER? EBC from 1995 to 2004 were evaluated. Annual hazard ratios (HR) for recurrence at different sites were calculated. Time-dependent Cox regression analysis was used to identify predictors of recurrence within 2.5 years of diagnosis, including factors that were more strongly predictive of early than later recurrence. Of 3,614 patients evaluated, 476 developed recurrence during the 5-year median follow-up. Cumulative recurrence rates at 2.5 years (95% confidence interval) were: overall 6.3% (5.5-7.1), locoregional 1.1% (0.7-1.5), contralateral 0.5% (0.3-0.7), and distant 4.8% (4.0-5.6). The annual HR of overall recurrence peaked at 2 years (4.3% per annum).The majority of this peak represented distant recurrence (3.4% per annum). In Cox regression analysis, tumor size and grade, lymph node involvement, lymphovascular invasion, and symptomatic presentation were significant independent predictors of early recurrence. Age at diagnosis was independently predictive of recurrence within 2.5 years of diagnosis but not later recurrence. This study identified an early recurrence peak at 2 years, most of which were distant recurrences. Implementing an aromatase inhibitor after an initial 2-3 years of tamoxifen fails to address this early peak of distant recurrence and the potential breast cancer-associated mortality.

Owing to its favourable tolerability profile versus cytotoxic chemotherapy, endocrine therapy is the treatment of choice for postmenopausal women with hormone receptor-positive advanced breast cancer (ABC). However, tolerability concerns associated with some endocrine treatments and the potential for cross-resistance has helped to drive the need for new, effective and better-tolerated agents. Fulvestrant is a new type of oestrogen receptor antagonist with no agonist effects. In phase III trials, fulvestrant has been shown to be at least as effective as the third-generation aromatase inhibitor (AI) anastrozole in the treatment of postmenopausal women with ABC progressing on prior tamoxifen therapy. Fulvestrant is administered as a once-monthly 250 mg intramuscular injection into the gluteus muscle. Here we review the tolerability of fulvestrant in the treatment of postmenopausal women with hormone-sensitive ABC and compare it with that of the four most frequently prescribed endocrine treatments for advanced disease (tamoxifen, anastrozole, letrozole and exemestane). Compared with these agents, fulvestrant is well tolerated and is associated with a lower incidence of joint disorders compared with the non-steroidal AIs and none of the potential androgenic side-effects that are sometimes seen with steroidal AIs. It is also associated with hot flushes compared with tamoxifen. Fulvestrant therefore provides clinicians and patients with a useful, well-tolerated option for the treatment of hormone-sensitive ABC. Integration of such agents into the endocrine treatment sequence may extend the opportunity for using well-tolerated therapies before chemotherapy needs to be considered and thus may improve quality of life for patients with ABC. The overall safety profiles of newer agents such as fulvestrant will become increasingly clear with their ongoing use.