Abstract
Breast cancer is the most common tumor in women worldwide, and an increasing public health concern. Knowledge of both protective and negative risk factors is essential for a better understanding of this heterogenous disease. We undertook a review of the recent literature and evaluated the relationship between obesity mediators and breast cancer development depending on menopausal status. Excess weight is now pandemic and has replaced tobacco as the main lifestyle-related risk factor for premature death. Although the prevalence of obesity/overweight has increased globally over the last 50 years, the potential harm attributable to excess fat has generally been underestimated. The relationship between overweight/obesity, breast cancer and overall risk appears to be highly dependent on menopausal status. Thus, obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women. We evaluate the role of different clinical factors potentially involved in this seemingly contradictory relationship, including estrogen, mammogram density, adipokines, insulin-signaling pathway activation, and inflammatory status. A key focus of this review is to better understand the impact of body mass index and menopausal status on these clinical factors and, hence, provide some clarity into the inter-relationships involved in this controversial issue.
Highlights
The incidence of obesity has nearly tripled since 1975 and it is considered one of the worst pandemics of the 21th century
Random fine needle aspirates of breast tissue were collected from 57 premenopausal and 55 postmenopausal healthy women classified as normal-weight, overweight, and obese
Obesity can have a marked impact in women since it is associated with an increased risk for many chronic conditions such as diabetes and heart disease, as well as it increases the risk of malignancies such as breast cancer
Summary
The incidence of obesity has nearly tripled since 1975 and it is considered one of the worst pandemics of the 21th century. The seemingly paradoxical relationship between obesity, breast density, and breast cancer risk lies in the fact that adiposity has a positive correlation with absolute nondense area and is a recognized risk factor for breast cancer, some reports indicate that absolute non-dense area correlates negatively with breast cancer risk [31] In this regard, Shieh et al reported that elevated MBD was associated with an increased risk of ER-negative breast cancer independent of menopausal status or BMI in premenopausal women [32]. Obesity may cause adipose tissue dysfunction, including secretion of abnormal levels of cytokines linked to insulin resistance, as well as impaired triglyceride storage and increased lipolysis These abnormalities may in turn contribute to accumulation of non-esterified fatty acids (NEFAs) in the circulation and an overload of NEFAs by skeletal muscle and liver cells, which are liable to instigate decreased insulin responsiveness in these tissues. Breast WAT inflammation is paralleled by increased tissue levels of aromatase (Figure 1) [70]
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