“Obesity-Associated” Breast Cancer in Lean Women: Metabolism and Inflammation as Critical Modifiers of Risk

Abstract

Why is obesity only weakly associated with certain "obesity-driven" cancers? Recent population studies identify cohorts of high body mass index (BMI) subjects with unexpectedly reduced risk for breast and colon cancer, and normal BMI subjects with unexpectedly elevated risk for breast cancer, provoking hard thinking about cellular and molecular mechanisms that most strongly couple obesity to cancer occurrence or progression. Emerging work suggests that abnormal metabolism and its associated chronic inflammation make the difference. Type II diabetes, for example, is a chronic inflammatory disease with specific imbalances in T-cell and myeloid-origin cytokines. Inflammation is elevated systemically, measured through blood biomarkers, and locally in adipose tissue. Here, cytokines and chemokines likely modify tumor microenvironments in dangerous ways. High BMI subjects with low inflammation and less disturbed metabolism appear to have reduced risk for certain obesity-associated cancers, whereas lean or slightly overweight subjects with high inflammation and metabolic abnormalities have elevated risk. This latter phenotype is prevalent among South Asian adults and suggests we are not monitoring certain normal weight adults sufficiently for risks of "obesity-associated" cancers. Profiling of patient metabolism and inflammation should accompany measures of body composition when considering cancer risk; the evidence base for these refinements must be extended through new, prospective observational studies.

Inflammatory signatures distinguish metabolic health in African American women with obesity

“…The study of obese subjects with and without T2D has demonstrated the utility of blood biomarkers for stratifying risk. However, even as the cardiometabolic and cancer risks of obesity are well appreciated, new work is focusing attention on overweight or normal weight women with abnormal metabolism and elevated inflammatory profiles [ 48 ], who may experience elevated risk for certain obesity-driven malignancies like breast cancer [ 49 ]. Even as we identified a novel group of cytokines and chemokines that independently associate with T2D risk, 48 of the other analytes tested were not significantly correlated with metabolic disease, which simplifies the task of developing personalized medicine profiles for high risk patients.…”

Obesidade e Câncer de mama: Algumas evidências científicas e vias de interação

“…Diversos estudos, principalmente epidemiológicos, têm evidenciado o papel do ambiente obesogênico e, portanto, da obesidade na promoção da neoplasia, e permitido que ao longo do tempo sejam elucidados os detalhes da relação ganho de peso e aumento do risco de câncer de mama principalmente na idade pós-menopáusica, embora a sua influência seja independente da menopausa (Denis & Palmer, 2017;Druso & Fischbach, 2018;Hao, et al, 2018). Pischon & Nimptsch (2015), em estudo realizado com obesos e eutróficos, observaram que os indivíduos classificados com obesidade apresentaram um risco de 1,5 a 3,5 vezes maior para o desenvolvimento de câncer, quando comparados ao outro grupo.…”

BET proteins in abnormal metabolism, inflammation, and the breast cancer microenvironment

“…More broadly, it is not yet possible to leverage our current knowledge of metabolic inflammation to understand cancer progression in different types of patients. Emerging critical opinion recognizes that the same subtype of cancer behaves quite differently depending on whether the patient is lean and metabolically normal, obese and diabetic, or lean and diabetic. In each case, the nature of T2D‐associated inflammatory cytokines and cellular infiltrates likely makes a critical difference.…”