A meta-analysis of endocrine therapy trials in early breast cancer (BC) evaluating the impact of obesity: Are aromatase inhibitors (AIs) optimal therapy in obese ER+ BC?

Authors

null

Lina Pugliano

Jules Bordet Institute, Breast International Group, Brussels, Belgium

Lina Pugliano , Dimitrios Zardavas , Marianne Paesmans , Ivana Sestak , Richard D. Gelber , Jack M. Cuzick , Mitchell Dowsett , Ahmad Awada , Martine J. Piccart-Gebhart , Evandro De Azambuja

Organizations

Jules Bordet Institute, Breast International Group, Brussels, Belgium, Institut Jules Bordet, Brussels, Université Libre de Bruxelles, Ixelles, Belgium, Brussels, Belgium, Institut Jules Bordet, Université Libre de Bruxelles, Ixelles, Belgium, Brussels, Belgium, Queen Mary, University of London, London, United Kingdom, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, IBCSG, Frontier Science and Technology Research Foundation, Boston, MA, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, London, United Kingdom, The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom, Medical Oncology Clinic, Jules Bordet Institute, Brussels, Belgium

Research Funding

No funding sources reported

Background: Obesity is an adverse prognostic factor in BC. Mixed results are reported for the relative efficacy of AIs compared to tamoxifen (T) in obese ER+ BC patients. Our purpose was to conduct a meta-analysis of adjuvant randomised trials of AIs vs T assessing the impact of body mass index (BMI). Methods: We identified four studies evaluating BMI and endocrine therapy. Of these, 3 were randomised (non-steroidal AIs vs T) and were evaluable for the aggregation of results for DFS and OS in our meta-analysis. We extracted published data from ATAC, ABCSG-12 and BIG01-98, analyzed according to standard meta-analytic techniques. Results: A total of 11,383 patients were included in our study. BMI>25 is associated with reduced disease free survival (DFS) and a trend towards worse overall survival (OS) (Table 1). A significantly shorter DFS was seen for patients with BMI>25 treated with an AI while a trend was seen for OS. Reduced relative efficacy was seen for DFS for AIs compared to T for BMI<25 (HR=0.78; 95%CI 0.66- 0.91; p=0.002) and a trend for BMI>25 (HR=0.85; 95%CI 0.70- 1.02; p=0.08). The test for interaction was not significant (p=0.48), with similar results for OS for BMI<25 (HR=0.79; 95%CI 0.63-0.9; p=0.009) and BMI>25 (HR=0.98; 95%CI 0.61-1.60; p=0.95). The test for interaction was not significant (p=0.37). Notably, significant heterogeneity in patients treated with anastrozole and a BMI>25 did not allow a comparison between anastrozole and letrozole. Conclusions: BMI>25 has a negative prognostic effect in BC. AIs demonstrate improved outcomes in normal weight BC patients (BMI<25). Obesity was associated with observed relative reduced efficacy of AIs; however, we were not able to detect a significant interaction between BMI and treatment effect. Further analyses into the differing impact of type of AIs on BC outcomes in obese patients are warranted.

HR 95%CI P value
DFS DMI>25 vs <25 1.09 1.00-1.19 0.04
OS BMI>25 vs <25 1.12 0.97-1.29 0.12
DFS AI treated patients BMI>25 vs <25 1.21 1.07-1.39 0.003
OS AI treated patients BMI>25 vs <25 1.44 0.76-2.74 0.26
DFS T treated patients BMI>25 vs <25 1.01 0.90-1.14 0.84
OS T treated patients BMI>25 vs <25 1.08 0.88-1.33 0.45

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Abstract Details

Meeting

2013 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Breast Cancer - HER2/ER

Track

Breast Cancer

Sub Track

ER+

Citation

J Clin Oncol 31, 2013 (suppl; abstr 575)

DOI

10.1200/jco.2013.31.15_suppl.575

Abstract #

575

Poster Bd #

5F

Abstract Disclosures