Local Biomarkers Involved in the Interplay between Obesity and Breast Cancer

Abstract

Obesity is associated with an increased risk of breast cancer, which is the most common cancer in women worldwide (excluding non-melanoma skin cancer). Furthermore, breast cancer patients with obesity have an impaired prognosis. Adipose tissue is abundant in the breast. Therefore, breast cancer develops in an adipose-rich environment. During obesity, changes in the local environment in the breast occur which are associated with breast cancer. A shift towards a pro-inflammatory state is seen, resulting in altered levels of cytokines and immune cells. Levels of adipokines, such as leptin, adiponectin, and resistin, are changed. Aromatase activity rises, resulting in higher levels of potent estrogen in the breast. Lastly, remodeling of the extracellular matrix takes place. In this review, we address the current knowledge on the changes in the breast adipose tissue in obesity associated with breast cancer initiation and progression. We aim to identify obesity-associated biomarkers in the breast involved in the interplay between obesity and breast cancer. Hereby, we can improve identification of women with obesity with an increased risk of breast cancer and an impaired prognosis. Studies investigating mammary adipocytes and breast adipose tissue in women with obesity versus women without obesity are, however, sparse and further research is needed.

Brief Post-Surgical Stress Management Reduces Pro-Inflammatory Cytokines in Overweight and Obese Breast Cancer Patients Undergoing Primary Treatment

“…Thus, although both OW/OB and NW women receiving stress management interventions reported significantly greater confidence in their ability to manage stress, unique processes occurred within OW/OB women resulting in decreased IL-6 levels over the study period. It is likely that OW/OB women, who presented with significantly higher IL-6 at baseline, were more able to benefit physiologically from a stress management intervention due to the co-occurring, and potentially interacting, effects of acute stress [38], chronic stress [39], and adiposity [24][25][26][27][28][29] on neuroendocrine regulation and inflammation. Providing coping and relaxation techniques may have been more impactful in this particularly vulnerable population.…”

“…Accordingly, obesity has been consistently linked to greater inflammation [23][24][25][26][27][28]. High adiposity in OW/OB individuals is associated with dysregulated metabolic pathways [23], including increased secretion of pro-inflammatory cy-tokines [24][25][26][27][28][29] and adipokines [27,29]. This increased inflammation related to adipose tissue dysfunction has been linked to increased BC risk in OW/OB women [30].…”

The Emerging Role of Cyclin-Dependent Kinase Inhibitors in Treating Diet-Induced Obesity: New Opportunities for Breast and Ovarian Cancers?

“…Regarding the potential introduction of CDKi drugs for the management of obesity, it would be important to estimate the anti-DIO effect in several cohorts of patients treated with CDK4/6 antagonists, as well as to identify which biomarkers could be the most useful to detect and quantify the connection existing between the anti-obesogenic role of a specific molecule and the achieved antitumoral effect. An example of these biomarkers linking both diseases has been recently reviewed last year [ 11 ], where the authors have deeply examined the accumulation of reactive oxygen species (ROS) and other free radicals responsible for causing DNA damage in DIO and cancer, some of them already outlined in this review (p.e. adipokines and cytokines).…”

“…Obesity is also a well-established risk factor for breast cancer (BC) [ 11 ] and ovarian cancer (OC) [ 12 ], which are among the most commonly diagnosed tumors in women worldwide, and a leading cause of cancer mortality [ 13 , 14 , 15 , 16 ]. Although epidemiologic data have associated obesity with increased risk of cancer development and progression for a variety of tumors long ago, only recently the underlying molecular mechanisms have begun to be characterized [ 17 , 18 ].…”

Greater Body Fatness Is Associated With Higher Protein Expression of LEPR in Breast Tumor Tissues: A Cross-Sectional Analysis in the Women’s Circle of Health Study

“…the local organ might have differential impacts on breast cancer based on tumor subtype, and the crosstalk between ER and adipokine biomarkers and other inflammatory biomarkers might play a role (59).…”