General and abdominal obesity and survival among young women with breast cancer
ABSTRACT Among postmenopausal women, obesity is linked to increased risk of breast cancer and poorer subsequent survival. For premenopausal women, obesity may reduce incidence, but less is known about its effect on prognosis, particularly for abdominal obesity. This study investigated whether general or abdominal obesity at diagnosis influenced survival in a cohort of young women with breast cancer. A population-based follow-up study was conducted among 1,254 women ages 20 to 54 who were diagnosed with invasive breast cancer between 1990 and 1992 in Atlanta or New Jersey. Women were interviewed within several months of diagnosis and asked about their weight and height at age 20 and in the year before diagnosis. Study personnel did anthropometric measures at the interview. With 8 to 10 years of follow-up, all-cause mortality status was determined using the National Death Index (n = 290 deaths). Increased mortality was observed for women who were obese [body mass index (BMI), > or =30] at the time of interview compared with women of ideal weight [BMI, 18.5-24.9; stage- and income-adjusted hazard ratio (HR), 1.48; 95% confidence interval (95% CI), 1.09-2.01]. A similar result was seen for the highest versus lowest quartile of waist-to-hip ratio (HR, 1.52; 95% CI, 1.05-2.19). Strong associations with mortality were found for women who were obese at age 20 (HR, 2.49; 95% CI, 1.15-5.37) or who were overweight/obese (BMI, > or =25) at both age 20 and the time of interview (HR, 2.22; 95% CI, 1.45-3.40). This study provides evidence that breast cancer survival is reduced among younger women with general or abdominal obesity.
SourceAvailable from: Meng-Hua Tao[Show abstract] [Hide abstract]
ABSTRACT: In spite of its public health importance, our understanding of the mechanisms of breast carcinogenesis and progress is still evolving. The metabolic syndrome (MS) is a constellation of biochemical abnormalities including visceral adiposity, hyperglycemia, hyperinsulinemia, dyslipidemia and high blood pressure. The components of the MS have all been related to late-stage disease and even to a poor prognosis of breast cancer through multiple interacting mechanisms. In this review, we aim to present a summary of recent advances in the understanding of the contribution of the MS to breast cancer with the emphasis on the role of biomarkers of the MS in the prognosis of breast cancer.06/2010; 2(2):721-739. DOI:10.3390/cancers2020721
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ABSTRACT: Inflammation of the adipose tissues occurs in association with obesity. This inflammatory process leads to the induction of cyclooxygenase-2 (COX-2) expression and a consequent elevation in prostaglandin (PG) production, which, together with proinflammatory cytokines, induce aromatase expression and estrogen synthesis. Infiltrating macrophages support the growth of breast epithelial cells and vascular endothelial cells by producing a milieu of cytokines and growth factors. This scenario creates a microenvironment favorable to breast cancer growth and invasion. The eicosanoids promote further development and growth of breast cancers indirectly by the induction of aromatase, particularly in estrogen positive breast cancers, or by direct stimulatory effect of PGE2 and lipoxygenase (LOX) products on the more aggressive, estrogen-independent tumors. Beyond this, the local production of estrogens and proinflammatory cytokines which occurs in association with breast adipose tissue inflammation, and consequent activation of the estrogen receptor and nuclear factor-κB, provides a mechanism by which breast cancers develop resistance to selective estrogen receptor modulation and aromatase inhibitor therapy. The obesity-inflammation-eicosanoid axis in breast cancer does offer a therapeutic target for the prevention of relapse in breast cancer by improving the efficacy of antiaromatase therapy using COX/LOX inhibitors; however, careful consideration of menopausal status and obesity in patients is warranted.Journal of Mammary Gland Biology and Neoplasia 10/2013; DOI:10.1007/s10911-013-9299-z · 7.52 Impact Factor
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ABSTRACT: Obesity is the cause of a large proportion of breast cancer incidences and mortality in post-menopausal women. In obese people, elevated levels of various growth factors such as insulin and insulin-like growth factors (IGFs) are found. Elevated insulin level leads to increased secretion of estrogen by binding to the circulating sex hormone binding globulin (SHBG). The increased estrogen-mediated downstream signaling favors breast carcinogenesis. Obesity leads to altered expression profiles of various adipokines and cytokines including leptin, adiponectin, IL-6, TNF-α and IL-1β. The increased levels of leptin and decreased adiponectin secretion are directly associated with breast cancer development. Increased levels of pro-inflammatory cytokines within the tumor microenvironment promote tumor development. Efficacy of available breast cancer drugs against obesity-associated breast cancer is yet to be confirmed. In this review, we will discuss different adipokine- and cytokine-mediated molecular signaling pathways involved in obesity-associated breast cancer, available therapeutic strategies and potential therapeutic targets for obesity-associated breast cancer.Cytokine & growth factor reviews 10/2013; DOI:10.1016/j.cytogfr.2013.10.001 · 6.49 Impact Factor