Mechanistic Targets and Nutritionally Relevant Intervention Strategies to Break Obesity-Breast Cancer Links.

Ximena M Bustamante-Marin,Emily Devericks,Delisha A Stewart,Jenna L Merlino,Meredith S Carson,Stephen D Hursting

doi:10.3389/fendo.2021.632284

Ximena M Bustamante-Marin, Emily Devericks + Show 4 more

Open Access

https://doi.org/10.3389/fendo.2021.632284

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Abstract

The worldwide prevalence of overweight and obesity has tripled since 1975. In the United States, the percentage of adults who are obese exceeds 42.5%. Individuals with obesity often display multiple metabolic perturbations, such as insulin resistance and persistent inflammation, which can suppress the immune system. These alterations in homeostatic mechanisms underlie the clinical parameters of metabolic syndrome, an established risk factor for many cancers, including breast cancer. Within the growth-promoting, proinflammatory milieu of the obese state, crosstalk between adipocytes, immune cells and breast epithelial cells occurs via obesity-associated hormones, angiogenic factors, cytokines, and other mediators that can enhance breast cancer risk and/or progression. This review synthesizes evidence on the biological mechanisms underlying obesity-breast cancer links, with emphasis on emerging mechanism-based interventions in the context of nutrition, using modifiable elements of diet alone or paired with physical activity, to reduce the burden of obesity on breast cancer.

Highlights

Obesity is a state of increased adiposity defined by a body mass index (BMI) ≥ 30 kg/m2 [1]
Autocrine and paracrine signaling mechanisms drive anti- and pro-inflammatory signals within the tumor microenvironment, linking inflammation to tumor aggressiveness, disease progression and chemoresistance programs [92, 93]. This communication, which includes other stromal components, creates a milieu promoting genetic instability that enhances every aspect of Breast cancer (BC) progression from increasing proliferation, reducing apoptosis, and facilitating angiogenesis, migration, and metastasis [94]
The aggressive biology of the tumor microenvironment metabolically activated by dysregulated adipose tissues in the obese state reduces the efficacy of cancer treatments, posing greater challenges in patient care and disease management

Summary

INTRODUCTION

Obesity is a state of increased adiposity defined by a body mass index (BMI) ≥ 30 kg/m2 [1]. Autocrine and paracrine signaling mechanisms drive anti- and pro-inflammatory signals within the tumor microenvironment, linking inflammation to tumor aggressiveness, disease progression and chemoresistance programs [92, 93] This communication, which includes other stromal components (i.e., fibroblasts and tumor-adjacent normal tissue), creates a milieu promoting genetic instability that enhances every aspect of BC progression from increasing proliferation, reducing apoptosis, and facilitating angiogenesis, migration, and metastasis [94]. Regular exercise is linked to reducing intratumoral hypoxia favoring the accessibility of circulating immune cells to the tumor microenvironment, inhibiting tumor development and improving cancer treatment [127] Fatty acids, such as arachidonic acid and omega-3 fatty acids, have been found to have a role in breast cancer [128, 129]. Future interventions strategies will need to account for the multi-factored contributors, namely inflammation, when addressing this aspect of BC

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