Effect of change of body mass index (BMI) during therapy on the efficacy of endocrine therapy in premenopausal patients with breast cancer: An analysis of the ABCSG-12 trial.

514 Background: Aromatase inhibitors (AIs) are effective as adjuvant endocrine treatment in breast cancer (BC) patients. Recently, it has been argued that BMI at BC diagnosis impacts on the efficacy of endocrine therapy. Interventional trials try to identify a benefit on outcome by BMI change after BC diagnosis. As endocrine therapy may lead to an increase of body weight, we investigated the impact of BMI change during therapy on BC outcome. METHODS ABCSG-12 examined the efficacy of ovarian suppression using goserelin (3.6 mg q28d SC) in combination with anastrozole (ANA) or tamoxifen (TAM) ± zoledronic acid (ZOL 4 mg IV q6mo) in premenopausal women with endocrine-responsive BC. BMI was calculated using prospectively collected data on weight and height at study entry as well as every three months up to 3 years of endocrine treatment. Comparisons between BMI at study entry and BMI during therapy were done by Wilcoxon signed rank test. Comparisons of BMI changes between ANA and TAM were done by Kruskal-Wallis test. Cox regression models were used to analyse the impact of BMI change as a time dependent covariate on disease free survival (DFS). RESULTS BMI significantly increased in both treatment arms after 1, 2 and 3 years of therapy. The increase of BMI was significantly higher in patients treated with TAM compared to ANA after 1, 2 and 3 years (0.68 vs. 0.38 kg/m², 1.06 vs. 0.71 kg/m² and 1.10 vs. 0.74 kg/m², p<0.05). None of the Cox regression models showed an impact of BMI as a time dependent covariate on DFS. No difference regarding DFS could be observed comparing patients with an increase of weight by >0.5kg after 1 year to patients with no such increase in weight (HR 1.25, 95%CI 0.886 1.76, p=0.2). Increase or decrease of BMI could not be correlated to the amount of adverse events at any time during therapy. CONCLUSIONS BMI significantly increases in premenopausal patients during endocrine therapy, especially in those treated with TAM. As the change of BMI during therapy does not impact on disease outcome, the BMI at BC diagnosis seems to be much more important than any short-term change thereafter.