P1-08-02: Pre-Diagnosis Body Mass Index and Breast Cancer Prognosis and Survival: Report from the after Breast Cancer Pooling Project.
Authors: Kwan ML , Chen WY , Weltzien E , Beasley JM , Lu W , Nechuta SJ , Quesenberry CP , Pierce JP , Shu XO , Caan BJ 
Published: June 2012

Abstract
Background: A large body of evidence dating back over 30 years suggests that obese women have poorer survival after a breast cancer (BC) diagnosis compared to non-obese women. Despite most studies supporting an association of elevated risk of overall mortality with obesity, the relationship of obesity with risk of BC recurrence, BC mortality and non-BC mortality remains unclear. Furthermore, reports suggest that the association of BMI with BC outcomes may be U or J shaped, prompting the necessity of examining underweight and more severely obese women as independent groups. We conducted a pooled investigation of pre-diagnosis BMI and BC recurrence and survival using data from the After Breast Cancer Pooling Project (ABCPP). Materials and Methods: The ABCPP includes 14,950 BC survivors from four prospective cohorts (three US and one Shanghai, China) diagnosed from 1990–2006 with invasive primary AJCC Stage I-III BC at ages 20–83 years. A random effects meta-analysis was conducted to assess heterogeneity across studies and poolability of data. Delayed entry Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations of pre-diagnosis BMI (underweight &lt;18.5 kg/m2, normal 18.5-&lt;25 kg/m2, overweight 25-&lt;30 kg/m2, obese ≥30 kg/m2) with BC recurrence, BC death, non-BC death, and overall death, adjusted for age at diagnosis, stage, race/ethnicity, menopausal status, hormone receptor status, number of positive lymph nodes, treatment, smoking history, and comorbidity (diabetes, hypertension, and/or CVD). Subgroup analyses further divided the obesity group into obese (30-&lt;35 kg/m2), severely obese (35-&lt;40 kg/m2), and morbidly obese (≥40 kg/m2) categories.
Results: No heterogeneity in effect estimates by study was found. 2104 deaths (1416 BC-related) and 2320 recurrences were observed after a mean (SD) of 7.66 (3.95) years of follow-up. Both underweight and obese women had a statistically significant increased risk of overall death compared to normal-weight women (underweight HR=1.69; 95% CI: 1.25, 2.28 and obese HR=1.22; 95% CI: 1.08, 1.38; p for nonlinear association&lt;0.01). Similar associations were found for non-BC death. Obese but not underweight was associated with increased risk of BC death (HR=1.17; 95% CI: 1.01, 1.36) and recurrence (HR=1.11; 95% CI: 0.98, 1.26). When examining finer obesity categories, the morbidly obese women had the greatest risk for all outcomes (overall death HR=1.90; 95% CI: 1.48, 2.45; non-BC death HR= 3.27; 95% CI: 2.25, 4.77; BC death HR = 1.47; 95% CI: 1.05, 2.06; recurrence HR = 1.27; 95% CI: 0.95, 1.71). No effect modification was observed by menopausal status, hormone receptor status, chemotherapy, and smoking. In all analyses, overweight women had similar risk of outcomes compared to normal-weight women.
Discussion: In this large pooling study of nearly 15,000 BC survivors, we found that the association between BMI and BC outcomes, specifically overall death and non-BC death, was U shaped with both underweight and obese women at greatest risk. Morbidly obese women were at even greater risk compared to other obesity groups. Maintaining a healthy weight throughout adult life may be beneficial for BC prognosis and survival.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-02.