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

Abstract

512 Background: Aromatase inhibitors (AIs) are effective as adjuvant endocrine treatment in breast cancer (BC) patients. According to the hypothesis that overweight patients have higher levels of aromatase enzyme availability, BMI might have impact on the efficacy of AIs. In this retrospective analysis of ABCSG-12, we investigated the influence of BMI on the effectiveness of adjuvant endocrine therapy (tamoxifen versus anastrozole in combination with goserelin) in premenopausal BC patients. 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 the prospectively collected data on patients's height and weight at study entry. BMI definitions of the WHO were used: normal 18.5-24.9 kg/m2; overweight: BMI ≥ 25 kg/m2, underweight BMI ≤ 18.5 kg/m2). Disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier method, results were compared by using the log-rank test and Cox proportional hazard modelling. Results: 1,111 (64.0%) patients were normal weight and 573 (33.0%) were overweight. Fifty-two (3.0%) underweight patients were excluded from further analyses. At a median follow-up of 5 years, overweight patients treated with ANA showed significantly shorter DFS (HR 1.60, 95%CI 1.064 2.412 p = 0.02) and OS (HR 2.284, 95%CI 1.217 4.289 p = 0.008) compared to normal weight ANA patients. No differences in DFS or OS were observed between overweight and normal weight patients treated with TAM (p = 0.62 and p = 0.77, respectively). In overweight patients, ANA led to shorter DFS and OS compared to TAM (HR 0.625 95%CI 0.387 1.009 p = 0.052, and HR 0.336 95%CI 0.149 0.76, p = 0.006, respectively), whereas there was no difference regarding DFS (p = 0.53) and OS (p = 0.67) in the group of normal weight patients. Conclusions: BMI significantly impacts on the efficacy of anastrozole plus goserelin but not tamoxifen plus goserelin in the adjuvant endocrine treatment of premenopausal breast cancer patients, probably through influencing aromatase availability in fat tissue. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Novartis AstraZeneca, Novartis AstraZeneca, GlaxoSmithKline, Merck, Novartis, Roche