Abstract
Obesity-related breast cancer is an important threat that affects especially post-menopausal women. The link between obesity and breast cancer seems to be relying on the microenvironment generated at adipose tissue level, which includes inflammatory cytokines. In addition, its association with systemic endocrine changes, including hyperinsulinemia, increased estrogens levels, and hyperleptinemia may be key factors for tumor development. These factors may promote tumor initiation, tumor primary growth, tissue invasion, and metastatic progression. Although the relationship between obesity and breast cancer is already established, the different pathophysiological mechanisms involved are not clear. Obesity-related insulin resistance is a well-known risk factor for breast cancer development in post-menopausal women. However, the role of inflammation and other adipokines, especially leptin, is less studied. Leptin, like insulin, appears to be a growth factor for breast cancer cells. There exists a link between leptin and metabolism of estrogens and between leptin and other factors in a more complex network. As a result, obesity-associated hyperleptinemia has been suggested as an important mediator in the pathophysiology of breast cancer. On the other hand, recent data on the paradoxical effect of obesity on cancer immunotherapy efficacy has brought some controversy, since the proinflammatory effect of leptin may help the effect of immune checkpoint inhibitors. Therefore, a better knowledge of the molecular mechanisms that mediate leptin action may be helpful to understand the underlying processes which link obesity to breast cancer in post-menopausal women, as well as the possible role of leptin in the response to immunotherapy in obese patients.
Highlights
Reviewed by: Mila Pontremoli Salcedo, Federal University of Health Sciences of Porto Alegre, Brazil Mohamed Hosney, Cairo University, Egypt
Once STAT3 is bound to the receptor, it is phosphorylated by janus kinase 2 (JAK2) and STAT3 proteins dimerize, allowing their translocation to the nucleus
Cancer patients with overweight or obesity (BMI > 25) have shown to have a better response to treatment with anti-PD1/PD-L1 immune checkpoint inhibitors [124]. This beneficial effect of increased body mass index (BMI) has been demonstrated in obese patients with metastatic melanoma [125, 126], where a mechanism mediated by chronic inflammation and increased C-reactive protein concentration has been proposed [127]
Summary
Obesity-related breast cancer is an important threat that affects especially post-menopausal women. Its association with systemic endocrine changes, including hyperinsulinemia, increased estrogens levels, and hyperleptinemia may be key factors for tumor development. Obesity-related insulin resistance is a well-known risk factor for breast cancer development in post-menopausal women. A better knowledge of the molecular mechanisms that mediate leptin action may be helpful to understand the underlying processes which link obesity to breast cancer in post-menopausal women, as well as the possible role of leptin in the response to immunotherapy in obese patients. In the development of post-menopausal breast cancer, as happens with other tumors, obesity has been considered a major risk factor.
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