Obesity and survival among a cohort of breast cancer patients is partially mediated by tumor characteristics

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.

Role of Adipose Tissue-Derived Autotaxin, Lysophosphatidate Signaling, and Inflammation in the Progression and Treatment of Breast Cancer

“…There is good evidence that obesity is associated with the development of premenopausal triple-negative breast cancer [ 80 ]. In patients with confirmed breast cancers, obesity also increases the risk of metastasis, tumor recurrence, and mortality [ 81 , 82 ].…”

Effects of weight reduction on the breast cancer-related lymphedema: A systematic review and meta-analysis

“…Although numerous studies have reported a statistical association between obesity and BCRL [ [13] , [14] , [15] , [16] ], [ [13] , [14] , [15] , [16] ] the causal relation and underlying mechanisms remain unclear. Given that studies have reported that obesity increases patients’ risks of larger tumors and axillary lymph node invasion and is considered a negative prognostic factor [ 29 , 30 ], patients with obesity could have received more treatments associated with subsequent occurrence of BCRL. Thus, obesity could in fact be indirectly connected to BCRL.…”

Macrophage conditioned media promotes adipocyte cancer-association, which in turn stimulates breast cancer proliferation and migration

“…Obesity increases the risk of several types of cancer, including post-menopausal breast cancer 3 . It is also a poor prognosis marker for several cancers and causes increased death rates [4][5][6] . It is estimated that 14% of cancer deaths in men and 20% in women are related to obesity 5 .…”