Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial

Abstract

Background: To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial.

Methods: We evaluated 4895 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial who received at least some study medication (median follow-up 60.3 months). Bone fracture information (grade, cause, site) was collected every 6 months during trial treatment.

Results: The incidence of bone fractures was higher among patients treated with letrozole [228 of 2448 women (9.3%)] versus tamoxifen [160 of 2447 women (6.5%)]. The wrist was the most common site of fracture in both treatment groups. Statistically significant risk factors for bone fractures during treatment included age, smoking history, osteoporosis at baseline, previous bone fracture, and previous hormone replacement therapy.

Conclusions: Consistent with other trials comparing aromatase inhibitors to tamoxifen, letrozole was associated with an increase in bone fractures. Benefits of superior disease control associated with letrozole and lower incidence of fracture with tamoxifen should be considered with the risk profile for individual patients.

Trial registration: ClinicalTrials.gov NCT00004205.

Figures

Figure 1.

Subpopulation treatment effect pattern plot analysis of incidence of any bone fracture for letrozole versus tamoxifen among overlapping subpopulations defined according to age at study entry.

Figure 2.

Univariate Cox model analysis (hazard ratios for time to first bone fracture; letrozole versus tamoxifen) for relevant risk factors among patients with any bone fracture. The box size is proportional to the inverse of the standard error of the hazard ratio estimates. The horizontal line gives the 95% confidence interval.

Figure 3.

Cumulative incidence of first bone fracture with first disease-free survival (DFS) event as competing events. In the competing risk analysis, for patients who had DFS events before the first bone fracture, the probability of bone fracture at a later time (after the DFS event) was assumed to be zero.