Possible mechanisms linking obesity to breast cancer
In this review, several mechanisms by which obesity affects the development and prognosis of breast cancer will be described.
Host factors such as estrogenic activity are likely to play a key role in the development of breast cancer, while tumor- and treatment-related factors contribute to the poor prognosis of these women.
Host-related factors
Hormones Higher bioavailable concentrations of tumor-promoting hormones, such as estrogen and testosterone, may contribute to carcinogenesis and poor survival in obese breast cancer patients [16,17]. Mammary carcinogenesis may also be promoted by the concomitant hyperinsulinemia found in some obese women through increased levels of insulin-like growth factor and leptin. These substances and estrogen have a synergistic effect on mammary epithelial cells, promoting tumor migration and invasion, enhancing angiogenesis, and increasing the activity of aromatase and transcriptional factors [18,19]. At present, more research is needed to clarify these interactions.Nutrition
The complex relationship between obesity, nutrition, and breast cancer is only partly understood, despite the fact that an association between breast cancer risk and dietary factors has long been recognized and extensively researched [20]. Obesity in women presenting with breast cancer may be a marker of poor dietary habits such as an excess intake of saturated fat, which is a recognized factor for an adverse breast cancer prognosis [21]. Several large-scale nutrition interventions, including the WHEL (Women’s Healthy Eating and Living) study, and WINS (the Women’s Intervention Nutrition Study), have recently reported beneficial effects of healthy eating on the prognosis of breast cancer, while others have not confirmed this association [22–24].
Socioeconomic status
Socioeconomic deprivation is associated with both obesity and a poor breast cancer prognosis, suggesting that host factors such as cellular immunity and nutrition, which determine the metastatic and recurrence potential of breast cancer [25], are unfavorable in obese patients from low socioeconomic groups [26]. However, this has been disputed by other investigators, and the association between socioeconomic status and breast cancer outcome is yet to be fully explicated [27]. A recent Scottish study again confirmed the difference in breast cancer incidence rates between deprived and affluent women [28].
Physical activity
Robust evidence from large-scale, well-performed epidemiological studies confirms that breast cancer patients who undertake regular, moderate physical activity have a better outcome than their sedentary counterparts [29–31]. Obese patients are less likely to engage in regular physical activity than women of normal weight. While there is little direct evidence to show that lack of physical exercise leads to breast cancer development or a poor prognosis, there is strong evidence demonstrating that regular physical activity after a diagnosis of breast cancer reduces the risk of disease-related death by 50% [29–31]. The greatest benefit has been seen in women who performed the equivalent of walking 3–5 h/week at an average pace, regardless of obesity or weight loss after surgery [30].
Shape and build
Central obesity and an elevated waist–hip ratio are associated with an increased risk of breast cancer-related mortality [32]. In postmenopausal women, an elevated waist–hip ratio is associated with a significantly higher RR of dying from breast cancer compared with women with a normal ratio (RR 3.3, 95% CI 1.1–10.4) [33]. The exact mechanism underlying this is not fully understood, but increased bioavailability of estrogen and hyperinsulinemia have been proposed as possible mechanisms [16].
Amtul R Carmichael, MD
Russells Hall Hospital, Dudley, UK