Abstract
Obesity exerts adverse effects on breast cancer survival, but the means have not been fully elucidated. We evaluated obesity as a contributor to breast cancer survival according to tumor molecular subtypes in a population-based case–cohort study using data from the Surveillance Epidemiology and End Results (SEER) program. We determined whether obese women were more likely to be diagnosed with poor prognosis tumor characteristics and quantified the contribution of obesity to survival. Hazard ratios (HRs) and 95% confidence intervals (CI) were calculated via Cox multivariate models. The effect of obesity on survival was evaluated among 859 incident breast cancers (subcohort; 15% random sample; median survival 7.8 years) and 697 deaths from breast cancer (cases; 100% sample). Obese women had a 1.7- and 1.8-fold increased risk of stage III/IV disease and grade 3/4 tumors, respectively. Obese women with Luminal A- and Luminal B-like breast cancer were 1.8 (95% CI 1.3–2.5) and 2.2 (95% CI 0.9–5.0) times more likely to die from their cancer compared to normal weight women. In mediation analyses, the proportion of excess mortality attributable to tumor characteristics was 36.1% overall and 41% and 38% for Luminal A- and Luminal B-like disease, respectively. Obesity was not associated with breast cancer-specific mortality among women who had Her2-overexpressing or triple-negative tumors. Obesity may influence hormone-positive breast cancer-specific mortality in part through fostering poor prognosis tumors. When tumor biology is considered as part of the causal pathway, the public health impact of obesity on breast cancer survival may be greater than previously estimated.
Highlights
In the U.S, almost 40% of the adult population is obese, and another 30% is overweight.[1,2] Obesity is one of the most prevalent modifiable risk factors for chronic disease and has received considerable attention in relation to cancer outcomes
We investigated the relationship between higher body mass index (BMI) and breast cancer survival, with consideration of the possibility that tumor characteristics were on the causal pathway, often termed “mediators.” We evaluated the BMI–mortality relationship according to breast cancer subtypes, as results from previous studies have suggested that the effect of BMI may be stronger in luminal disease.[9,10,11,12,13,14]
Mediation analysis Tumor characteristics differed by BMI (Table 2)
Summary
In the U.S, almost 40% of the adult population is obese, and another 30% is overweight.[1,2] Obesity is one of the most prevalent modifiable risk factors for chronic disease and has received considerable attention in relation to cancer outcomes. Despite numerous studies that have evaluated obesity and breast cancer-specific mortality, the means through which obesity exerts its effects on breast cancer survival have not been fully elucidated. In recent meta-analyses, breast cancer-specific death among obese women is elevated 1.3-fold compared to normal weight women.[3,4] in most studies, risk estimates for the relationship between body mass index (BMI) and breast cancer mortality have been adjusted for tumor characteristics (stage at diagnosis and/or tumor size, grade, and nodal status). Evidence is accumulating that tumor characteristics may be on the causal pathway (potential mediators) between BMI and cancer mortality.[5,6,7] If so, the BMI–mortality risk estimates adjusted for these factors is likely to be underestimated. Statistical adjustment for a causal intermediate can substantially attenuate risk estimates or even result in a reversal of direction (suggested reduced risk).[8]
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