When fat becomes an ally of the enemy: adipose tissue as collaborator in human breast cancer

2015 ◽  
Vol 23 (1) ◽  
Author(s):  
Lore Lapeire ◽  
Hannelore Denys ◽  
Véronique Cocquyt ◽  
Olivier De Wever
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Breast Cancer Incidence ◽  
Human Adipose Tissue ◽  
Menopausal Women ◽  
Cancer Types ◽  
Post Menopausal ◽  
Lateral Communication

AbstractSince the discovery of leptin in 1994, our vision of adipose tissue as a static organ regulating mainly lipid storage and release has been completely overthrown, and adipose tissue is now seen as an active and integral organ in human physiology. In the past years, extensive research has tremendously given us more insights in the mechanisms and pathways involved not only in normal but also in ‘sick’ adipose tissue, for example, in obesity and lipodystrophy. With growing evidence of a link between obesity and several types of cancer, research focusing on the interaction between adipose tissue and cancer has begun to unravel the interesting but complex multi-lateral communication between the different players. With breast cancer as one of the first cancer types where a positive correlation between obesity and breast cancer incidence and prognosis in post-menopausal women was found, we have focused this review on the paracrine and endocrine role of adipose tissue in breast cancer initiation and progression. As important inter-species differences in adipose tissue occur, we mainly selected human adipose tissue- and breast cancer-based studies with a short reflection on therapeutic possibilities. This review is part of the special issue on “Adiposopathy in Cancer and (Cardio)Metabolic Diseases”.

scholarly journals Review: The Emerging Role of Metformin as Aromatase Inhibitor in Breast Cancer

2019 ◽  
Vol 4 (2) ◽  
pp. 1-10
Author(s):  
Amrilmaen Badawi
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Aromatase Inhibitor ◽  
Aromatase Inhibitors ◽  
Antidiabetic Agent ◽  
Menopausal Women ◽  
Work Mechanism ◽  
Post Menopausal ◽  
Very High

The prevalence of breast cancer is still very high among women, in particular post-menopausal women. There are many factors contributed to the diseases, including diabetes. Recently, it has been emerged that metformin, an antidiabetic agent, is capable of reducing the risk of developing breast cancer among post-menopausal women, and act as aromatase inhibitors (AIs) which inhibits the production of estrogen. In this review, we focus in discussing the possible work mechanism of metformin as AIs and what is in the pipeline on clinical trials.

Tamoxifen and Endometrial Cancer

1996 ◽  
Vol 3 (2) ◽  
pp. 107-112 ◽  
Author(s):  
Richard R. Barakat
Keyword(s):  
Breast Cancer ◽  
Endometrial Cancer ◽  
Large Scale ◽  
Early Stage ◽  
Tamoxifen Treatment ◽  
Breast Cancer Patients ◽  
Menopausal Women ◽  
Overall Survival Benefit ◽  
Post Menopausal

Tamoxifen is commonly used in the management of patients with breast cancer. Clinical trials of tamoxifen involving over 75,000 patients demonstrate an improved recurrence-free and overall survival benefit in both pre- and post-menopausal women. Large-scale trials also are evaluating the role of tamoxifen as a chemopreventive agent in women considered to be at high risk for developing breast cancer based on family history. Endometrial cancer is an uncommon complication of tamoxifen therapy. Since the majority of these cancers will be detected at an early stage when they are highly curable, however, the overall benefit of tamoxifen treatment in breast cancer patients outweighs this risk. All women receiving tamoxifen who have a uterus should undergo regular gynecologic examinations.

scholarly journals A comparison of time to event analysis methods, using weight status and breast cancer as a case study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Georgios Aivaliotis ◽  
Jan Palczewski ◽  
Rebecca Atkinson ◽  
Janet E. Cade ◽  
Michelle A. Morris
Keyword(s):  
Breast Cancer ◽  
Machine Learning ◽  
Cohort Study ◽  
Weight Status ◽  
Cox Model ◽  
Breast Cancer Incidence ◽  
Time To Event ◽  
Menopausal Women ◽  
Post Menopausal ◽  
Partial Dependence

AbstractSurvival analysis with cohort study data has been traditionally performed using Cox proportional hazards models. Random survival forests (RSFs), a machine learning method, now present an alternative method. Using the UK Women’s Cohort Study (n = 34,493) we evaluate two methods: a Cox model and an RSF, to investigate the association between Body Mass Index and time to breast cancer incidence. Robustness of the models were assessed by cross validation and bootstraping. Histograms of bootstrap coefficients are reported. C-Indices and Integrated Brier Scores are reported for all models. In post-menopausal women, the Cox model Hazard Ratios (HR) for Overweight (OW) and Obese (O) were 1.25 (1.04, 1.51) and 1.28 (0.98, 1.68) respectively and the RSF Odds Ratios (OR) with partial dependence on menopause for OW and O were 1.34 (1.31, 1.70) and 1.45 (1.42, 1.48). HR are non-significant results. Only the RSF appears confident about the effect of weight status on time to event. Bootstrapping demonstrated Cox model coefficients can vary significantly, weakening interpretation potential. An RSF was used to produce partial dependence plots (PDPs) showing OW and O weight status increase the probability of breast cancer incidence in post-menopausal women. All models have relatively low C-Index and high Integrated Brier Score. The RSF overfits the data. In our study, RSF can identify complex non-proportional hazard type patterns in the data, and allow more complicated relationships to be investigated using PDPs, but it overfits limiting extrapolation of results to new instances. Moreover, it is less easily interpreted than Cox models. The value of survival analysis remains paramount and therefore machine learning techniques like RSF should be considered as another method for analysis.

scholarly journals The color of fat and its central role in the development and progression of metabolic diseases

2017 ◽  
Vol 31 (1) ◽  
Author(s):  
Melania Gaggini ◽  
Fabrizia Carli ◽  
Amalia Gastaldelli
Keyword(s):  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Subcutaneous Adipose Tissue ◽  
Metabolic Diseases ◽  
Caloric Intake ◽  
Human Adipose Tissue ◽  
Normal Weight ◽  
Metabolic Characteristics ◽  
Subcutaneous Adipose

AbstractExcess caloric intake does not always translate to an expansion of the subcutaneous adipose tissue (SAT) and increase in fat mass. It is now recognized that adipocyte type (white, WAT, or brown, BAT), size (large vs. small) and metabolism are important factors for the development of cardiometabolic diseases. When the subcutaneous adipose tissue is not able to expand in response to increased energy intake the excess substrate is stored as visceral adipose tissue or as ectopic fat in tissues as muscle, liver and pancreas. Moreover, adipocytes become dysfunctional (adiposopathy, or sick fat), adipokines secretion is increased, fat accumulates in ectopic sites like muscle and liver and alters insulin signaling, increasing the demand for insulin secretion. Thus, there are some subjects that despite having normal weight have the metabolic characteristics of the obese (NWMO), while some obese expand their SAT and remain metabolically healthy (MHO). In this paper we have reviewed the recent findings that relate the metabolism of adipose tissue and its composition to metabolic diseases. In particular, we have discussed the possible role of dysfunctional adipocytes and adipose tissue resistance to the antilipolytic effect of insulin on the development of impaired glucose metabolism. Finally we have reviewed the possible role of BAT vs. WAT in the alteration of lipid and glucose metabolism and the recent studies that have tried to stimulate browning in human adipose tissue.

Treatment of established breast cancer in post-menopausal women: Role of aromatase inhibitors

The Surgeon ◽  
2009 ◽  
Vol 7 (1) ◽  
pp. 42-55 ◽  
Author(s):  
S. Samphao ◽  
J.M. Eremin ◽  
M. El-Sheemy ◽  
O. Eremin
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Menopausal Women ◽  
Post Menopausal

scholarly journals Long-Term Whole Grain Wheat and Rye Intake Reflected by Adipose Tissue Alkylresorcinols and Breast Cancer: A Case-Cohort Study

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 465 ◽  
Author(s):  
Huaxing Wu ◽  
Cecilie Kyrø ◽  
Anne Tjønneland ◽  
Katja Boll ◽  
Anja Olsen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Adipose Tissue ◽  
Cohort Study ◽  
Breast Cancer Incidence ◽  
Case Group ◽  
Whole Grain ◽  
Estrogen Receptor Positive

Whole grain rye (WGR) and whole grain wheat (WGW) have been suggested to protect against the development of breast cancer. In this study, we estimated long-term intake of WGR and WGW, using both a food frequency questionnaire (FFQ) and alkylresorcinol concentrations in adipose tissue biopsies, in relation to the risk of developing invasive breast cancer in a case-cohort study (n = 414 in the case group, n = 933 in the subcohort group) on the Danish “Diet, Cancer and Health” cohort. The median follow-up time of the subcohort was 5.3 years. Total WGR and WGW intake estimated with FFQ or reflected by total alkylresorcinol concentration in adipose tissue was not significantly associated with risk of breast cancer. However, after adjustment for total WGR and WGW intake, women in the highest quartile of relative WGR intake, reflected by the alkylresorcinol C17:0/C21:0 ratio, had a higher risk of overall breast cancer and estrogen-receptor-positive (ER+) breast cancer than women in the lowest quartile of relative WGR intake, while the risk of estrogen-receptor-negative (ER-) breast cancer incidence was unaffected. Similar results were obtained with the FFQ data. Based on these data, further investigation of the role of specific grain types in reducing or increasing breast cancer risk, and their overall impact on health, is warranted.

New insights into purine metabolism in metabolic diseases: role of xanthine oxidoreductase activity

2020 ◽  
Vol 319 (5) ◽  
pp. E827-E834 ◽  
Author(s):  
Masato Furuhashi
Keyword(s):  
Adipose Tissue ◽  
Uric Acid ◽  
Metabolic Diseases ◽  
Tissue Injury ◽  
Human Adipose Tissue ◽  
Purine Metabolism ◽  
Xanthine Oxidoreductase ◽  
Oxidoreductase Activity ◽  
Atp Production

Xanthine oxidoreductase (XOR) consists of two different forms, xanthine dehydrogenase and xanthine oxidase (XO), and is a rate-limiting enzyme of uric acid production from hypoxanthine and xanthine. Uric acid is the end product of purine metabolism in humans and has a powerful antioxidant effect. The lack of ascorbic acid, known as vitamin C, in hominoids has been thought to cause a compensatory increase in uric acid as an antioxidant by unfunctional gene mutation of uricase to a pseudogene. Because XO is involved in an increase in reactive oxygen species (ROS) by generating superoxide and hydrogen peroxide, inadequate activation of XOR promotes oxidative stress-related tissue injury. Plasma XOR activity is associated with obesity, smoking, liver dysfunction, hyperuricemia, dyslipidemia, insulin resistance, and adipokines, indicating a novel biomarker of metabolic disorders. However, XOR activity in adipose tissue is low in humans unlike in rodents, and hypoxanthine is secreted from human adipose tissue. The concentration of hypoxanthine, but not xanthine, is independently associated with obesity in a general population, indicating differential regulation of hypoxanthine and xanthine. Treatment with an XOR inhibitor can decrease uric acid for preventing gout, reduce production of XO-related ROS, and promote reutilization of hypoxanthine and ATP production through the salvage pathway. It has recently been suggested that discontinuation of an XOR inhibitor causes adverse cardiovascular outcomes as XOR inhibitor withdrawal syndrome, possibly due to cardiac disturbance of conduction and contraction by reduced ATP production. New insights into purine metabolism, including the role of XOR activity in the past 5 yr, are mainly discussed in this review.

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