Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention

Abstract

Recent decades have seen an unprecedented rise in obesity and the health impact thereof is increasingly evident. In 2014, worldwide more than 1.9 billion adults were overweight (BMI 25–29.9kg/m2) and of these over 600 million were obese (BMI≥30kg/m2). While the association between obesity and risk of diabetes and coronary artery disease is widely known, the impact of obesity on cancer incidence, morbidity and mortality is not fully appreciated. Obesity is associated with a higher risk of developing breast cancer, particularly in postmenopausal women, and is associated with worse disease outcome for women of all ages. The first part of this review summarizes the relationships between obesity and breast cancer development and outcome in pre and postmenopausal women and in hormone receptor positive and negative disease. The second part of this review addresses hypothesized molecular mechanistic insights that may underlie the effects of obesity to increase local and circulating pro-inflammatory cytokines that promote tumor angiogenesis, and stimulate the most malignant cancer stem cell population to drive cancer growth, invasion and metastasis. Finally, we review observational studies showing that increased physical activity associates with lower breast cancer risk and better outcome. We discuss effects of recent lifestyle interventions to decrease sex steroids, insulin/IGF-1 pathway activation and inflammatory biomarkers associated with worse breast cancer outcome in obesity. Although many observational studies show that exercise with weight loss associates with improved breast cancer outcome, further prospective studies are needed to determine if weight reduction will lead to improved patient outcome. It is hoped that several ongoing lifestyle intervention trials, reviewed herein, will support the systematic incorporation of weight loss intervention strategies into breast cancer patient care.

Nutritional and environmental risk factors for breast cancer: a case-control study

“…Another classic risk factor for the diagnosis of breast cancer is overweight (including obesity) [30,31], and the present data corroborates this assertion. A study among survivors also observed a high prevalence of overweight status in 154 patients from a reference center in Brazil [32].…”

Body Mass Index at Diagnosis as a Prognostic Factor for Early-Stage Invasive Breast Cancer after Surgical Resection

“…In an observational prospective study consisting of about 350,000 US women, higher BMI was very significantly associated with increased risk of death from breast cancer [6]. Although the impact of obesity on diabetes and heart disease is well known, its effect on cancer remains largely unexplored in clinical practice [7, 8]. …”

Low BMI is correlated with increased TGF‐β and IL‐10 mRNA levels in the peripheral blood of breast cancer patients

“…On the contrary, fat tissue shows increased levels of leptin, resulting in low TGF‐β and IL‐10 levels. However, obese breast cancer patients still have higher mortality, which may be a result of the association between obesity and increased tumor size, positive lymph node involvement, and triple‐negative subtype, but not the secretion of TGF‐β and IL‐10 . Other nutritional parameters were not significantly associated with levels of TGF‐β, IL‐10 and Foxp3, potentially because there is a nondirect correlation between them in terms of biological mechanism.…”