The Many Faces of Obesity and Its Influence on Breast Cancer Risk

Abstract

Obesity is associated with increased risk of breast and other cancers. However, the complexity of the underlying mechanisms, together with the interplay of diet and physical activity-contributing to energy balance-and the role of adipose tissue, pose challenges to our understanding of the basis of this increased risk. Epidemiologic studies have documented a higher obesity prevalence in US black women compared to white women. Elucidation of the contribution of potential biological differences among racially distinct groups to their differences in breast cancer (BC) risk and mortality have been topics of considerable interest in recent years. The racial and ethnic variation in body fat distribution may account for at least part of the differences in breast cancer rates in these populations. Yet, while black women exhibit higher rates of obesity compared to white women, this does not translate directly into higher rates of BC. In fact, overall, BC in black women occurs with a lower incidence than BC in white women. Obesity is a known risk factor for postmenopausal breast cancer, and growing evidence suggests that abdominal obesity, also known as central obesity, may increase risk for triple negative breast cancer, which is more common in premenopausal women. The positive association of postmenopausal BC risk and specifically estrogen receptor (ER)-positive BC, is presumably due largely to accumulation of estrogen in the adipose tissue of the breast and other tissues. Of the two main types of adipose tissue-subcutaneous and visceral-visceral adipocytes are more active metabolically. Such adipose tissue harbors multiple molecular entities that promote carcinogenesis: endocrine molecules/hormones, immunologic factors, inflammatory cytokines, metabolic alterations, and other components of the microenvironment. Expression of these culpable entities is largely regulated by epigenetic mechanisms. The interrelationship between these entities and drivers of epigenetic alteration are critical to the regulation of pathways connecting obesity and cancer risk. Initiatives to counteract the carcinogenic effects of obesity have primarily involved modulation of energy balance by diet. However, targeting of specific molecular abnormalities characterizing adiposity offers an alternative approach to preventing cancer. Our goal in this review is to first discuss the major mechanisms contributing to the obesity-breast cancer link. We will also consider race, specifically black/white differences, as they relate to the association of obesity with breast cancer risk. Then we will enumerate strategies targeting these mechanisms to reduce BC risk, in large part by way of dietary interventions with potential to mitigate the cancer-promoting components of adiposity.

Oxidative Stress, Nutrition and Cancer: Friends or Foes?

“…The common routinely pathway is indicated in the centre of the figure (large thick arrows), suggesting the pathway pre-adipocyte-mature adipocyte-delipided adipocyte, which then evolves to a post-adipocyte. This can give rise to adipocytes (1), adipocyte derived stem cells (ADSCs), which then will evolve to adipocytes directly (2) or via a pre-adipocytic pathway (3). Moreover, mature adipocytes can evolve to dedifferentiated adipose tissue (DFAT) cells (4), which might be confused with the stem pool of fibrblast-like cells.…”

“…The great concern of cancer worldwide is expanding its shadows to scientific fields previously far from a forthright relation with oncology. Besides to the awareness that malnutrition and some incorrect dietary habits and lifestyles are possible triggers for cancer onset, current literature is moving its spotlight on the fundamental role exerted by the different adipose tissues in this regards [ 1 2 3 ]. The adipocyte is a highly complex cell, despite its simplistic image of a fat-collecting tank.…”

Flavonoids and Other Polyphenols Act as Epigenetic Modifiers in Breast Cancer

“…According to the American Cancer Society, approximately 2 million new cases of breast cancer occurred worldwide in 2018 [1]. Major risk factors for breast cancer include genetic mutation, obesity, alcohol consumption, lack of physical activity, red meat consumption, and processed food intake [2][3][4][5]. However, a variety of factors provide prevention of breast cancer occurrence, including sustaining a healthy weight; consuming a diet rich in produce, whole grains, and beans; and limiting consumption of alcohol, red meat, fatty, salty, high sugar foods, and processed foods [6].…”

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

“…Obesity-driven BC risk is associated with multiple factors including menopausal status ( 12 ). Further, the risk of developing postmenopausal BC is exacerbated by obesity ( 13 ). These women have worse disease-free and overall survival despite appropriate therapeutic approaches.…”