[S2-1] Obesity at Diagnosis Is Associated with Inferior Outcomes in Hormone Receptor Positive Breast Cancer.

Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, Sledge GW, Wood WC, Fetting J, Davidson NE. Eastern Cooperative Oncology Group; Southwest Oncology Group; Cancer and Leukemia Group B; North Central Cancer Treatment Group

Background: Obesity has been associated with worse outcomes in operable breast cancer. We evaluated the effect of obesity on outcomes in several adjuvant trials coordinated by the ECOG which included doxorubicin/cyclophosphamide plus other agents, including E1199 (NEJM 2008; 358: 1663), E5188 (JCO 2005; 23: 5973) and E3189 (JCO 10998; 16: 2382).
Methods: The relationship between body mass index (BMI in kg/m2) and disease free survival (DFS) and overall survival (OS) was evaluated in multivariate models adjusted for covariates including age, tumor size, nodal status, race (black vs. other), surgery type, prior RT, menopausal status, treatment arm, and treatment adherence. Results are expressed as hazard ratios (HR) from Cox's proportional hazards models (HR > 1 indicates a worse outcome). All p-values are two sided.
Results: The study characteristics and results are shown in the table below. We first evaluated results for the E1199 trial (for the 75% of those with BMI data available) and found a non-significant trend toward inferior DFS (HR 1.10, 95% CI 0.96, 1.26, p=0.18) and OS (HR 1.13, 95% CI 0.96, 1.33, p=0.15) for obese subjects compared with others. When evaluated by breast cancer subtype, however, obese subjects with ER and/or PR-positive/HER2-negative disease had significantly inferior DFS (HR 1.24, p=0.026) and OS (HR 1.42, p=0.003), an effect that was not seen for HER2-positive and triple negative disease. In a model including obesity, ER and/or PR-pos/HER2-neg disease, and their interaction, the interaction term was significant for OS (p=0.017) but not DFS (p=0.21). There was no evidence for differing chemotherapy delivery or endocrine therapy adherence, or differences in toxicity for obese subjects in the E1199 trial. We then evaluated the relationship between obesity and outcomes in two prior ECOG studies which included only premenopausal women with ER positive, node positive breast cancer (E5188) and women of any age with ER/PR negative, node positive disease (E3189), and confirmed a relationship between obesity and poor outcomes only in women with hormone receptor positive disease.

StudyPopulationNoBMI > 30 kg/m2HR for DFSHR for OS
E1199All subjects348438%1.10 (p=0.18)1.13 (p=0.15)
E1199ER and/or PR+/HER2-211538%1.24 (p=0.026)1.42 (p=0.003)
E1199HER2+66136%1.07 (p=0.70)0.89 (p=0.55)
E1199ER/PR/HER2-70839%1.01 (p-0.93)1.05 (p=0.75)
E5188ER and/or PR+150125%1.46 (p<0.0001)1.52 (p<0.001)
E3189ER/PR-61031%0.91 (p=0.55)0.85 (p=0.84)
HR- hazard ratio; ER/PR- estrogen/progesterone receptor

Conclusions: Obesity was associated with significantly inferior DFS and OS in hormone receptor positive operable breast cancer treated with adjuvant chemotherapy. These findings suggest that hyperinsulinemia or other factors associated with obesity may predispose to recurrence specifically in hormone receptor positive disease, and requires further evaluation in prospective studies in order to identify modifiable factors contributing to this effect.

Thursday, December 9, 2010 2:45 PM

General Session 2 (2:45 PM-4:30 PM)

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