Obesity and breast cancer: role of inflammation and aromatase

Simpson, Evan R.; Brown, Kristy A.

doi:10.1530/jme-13-0217

Cited by 80 publications

(85 citation statements)

References 45 publications

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“…In postmenopausal women, adipose tissue becomes the major production site for estrogens via the enzyme aromatase which is expressed by the stromal cell fraction [35]. As obese postmenopausal women usually exhibit elevated estrogen levels, they are at risk of developing estrogen-dependent breast cancer.…”

Section: Pathophysiology Of the Association Between Metabolic Syndrommentioning

confidence: 99%

Metabolic Syndrome and Breast Cancer: Is There a Link?

Hauner

2014

Breast Care

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Summary Epidemiological data suggest a close link between obesity and breast cancer, the most frequently occurring cancer in women. The metabolic syndrome is typically associated with abdominal obesity and comprises disturbances in glucose and/or lipid metabolism and/or hypertension. Recent studies have established a specific association between the metabolic syndrome - as well as its components - and breast cancer, indicating both an increased risk of developing breast cancer and a poorer prognosis. In premenopausal women, obesity might have a protective effect only on receptor-positive tumors, whereas a positive association was observed between obesity/abdominal obesity and an increased risk of triple-negative breast cancer (TNBC). Overall survival and disease-free survival were reported to be significantly shorter in premenopausal obese women with TNBC compared to non-obese women, but these results are still inconsistent and need further research. The metabolic syndrome is characterized by a state of insulin resistance/hyperinsulinemia and subacute chronic inflammation, with both conditions offering a plausible mechanistic link towards breast cancer. Thus, in addition to their increased risk of cardiovascular morbidity and mortality, women with this syndrome represent a group at elevated risk of developing breast cancer and with poorer prognosis.

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Section: Pathophysiology Of the Association Between Metabolic Syndrommentioning

confidence: 99%

Metabolic Syndrome and Breast Cancer: Is There a Link?

Hauner

2014

Breast Care

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“…7). In normal breast adipose tissue, aromatase gene expression is mainly under the control of the distal promoter PI.…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin E2 Inhibits p53 in Human Breast Adipose Stromal Cells: A Novel Mechanism for the Regulation of Aromatase in Obesity and Breast Cancer

et al. 2015

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Obesity is a risk factor for postmenopausal breast cancer and the majority of these cancers are estrogen dependent. Aromatase converts androgens into estrogens and its increased expression in breast adipose stromal cells (ASC) is a major driver of estrogen receptor-positive breast cancer. In particular, obesity-associated and tumor-derived factors, such as prostaglandin E 2 (PGE 2 ), have been shown to drive the expression of aromatase by stimulating the activity of the proximal promoter II (PII). The tumor-suppressor p53 is a key regulator of cell-cycle arrest and apoptosis and is frequently mutated in breast cancer. Mutations in p53 are rare in tumor-associated ASCs. Therefore, it was hypothesized that p53 is regulated by PGE 2 and involved in the PGE 2 -mediated regulation of aromatase. Results demonstrate that PGE 2 causes a significant decrease in p53 transcript and nuclear protein expression, as well as phosphorylation at Ser15 in primary human breast ASCs. Stabilization of p53 with RITA leads to a significant decrease in the PGE 2 -stimulated aromatase mRNA expression and activity, and PII activity. Interaction of p53 with PII was demonstrated and this interaction is decreased in the presence of PGE 2 . Moreover, mutation of the identified p53 response element leads to an increase in the basal activity of the promoter. Immunofluorescence on clinical samples demonstrates that p53 is decreased in tumor-associated ASCs compared with ASCs from normal breast tissue, and that there is a positive association between perinuclear (inactive) p53 and aromatase expression in these cells. Furthermore, aromatase expression is increased in breast ASCs from Li-Fraumeni patients (germline TP53 mutations) compared with non-Li-Fraumeni breast tissue. Overall, our results demonstrate that p53 is a negative regulator of aromatase in the breast and its inhibition by PGE 2 provides a novel mechanism for aromatase regulation in obesity and breast cancer. Cancer Res; 75(4); 645-55.Ó2015 AACR.

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“…Thus, reducing the obesity-induced inflammatory response is one of the proposed approaches for chemoprevention (60)(61)(62).…”

Section: Obesity and Cancermentioning

confidence: 99%

A Narrative Review of Obesity and Its Associated Complications in Iranian Women

Mirmiran¹,

Ghorbani²,

Hosseini-Esfahani³

2017

Women Health Bull

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Context: Obesity is a major public health problem worldwide. This review aimed at providing an updated overview of obesity in Iranian women and its associated complications. Evidence Acquisition: In this narrative review study, related systematic reviews or meta-analysis studies of high ranking journals conducted from 2000 to 2016 were searched in the PubMed, Medline, and Scopus with the following keywords: "women OR female" AND "weight OR overweight OR obesity", "risk factors OR complications", "reproduction OR cancer OR cardiovascular disease OR diabetes OR gestational diabetes OR maternal obesity OR fertility OR pregnancy OR polycystic ovary syndrome" OR management. Results: In Iran, women have shown a constantly higher risk of obesity compared to men. After a 9-year follow-up, the agestandardized incidence rate (95% CI) of diabetes was 10.1 (7.24 -13.9) in women. The increases in overweight and obesity in menopausal women have an important role in endometrial, colon, and breast cancer. Obesity increases the risk of endometrial cancer 2.4 to 4.5 folds compared to the normal weight women. Maternal obesity increases the risk of gestational hypertension 4.5 to 8.7 times compared to normal weight women. An increasing number of obese women becoming pregnant is associated with shortand long-term maternal and child outcomes. The prevalence of childhood obesity in children of obese women aged 3 to 5 years increases up to 25%; and these children have an almost 6-fold chance of being obese in young adulthood. Weight reduction of obese women is accompanied with lower incidence of obesity complications. The most effective interventions are multiple behavioral management activities. Conclusions:Considering the large population of young people in Iran and the lack of any effective preventive policy, the burden of obesity and its associated outcomes will be problematic in the near future.

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Obesity and breast cancer: role of inflammation and aromatase

Abstract: Obesity is now recognised to be an inflammatory condition in which dysregulated metabolism plays an integral role. Inflammatory mediators regulate aromatase expression in the human breast as one mechanism whereby they increase the risk of breast cancer, especially in women who are obese.

Cited by 80 publications

References 45 publications

Metabolic Syndrome and Breast Cancer: Is There a Link?

Metabolic Syndrome and Breast Cancer: Is There a Link?

Prostaglandin E2 Inhibits p53 in Human Breast Adipose Stromal Cells: A Novel Mechanism for the Regulation of Aromatase in Obesity and Breast Cancer

A Narrative Review of Obesity and Its Associated Complications in Iranian Women

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