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Review
. 2021 Mar 25:11:629666.
doi: 10.3389/fonc.2021.629666. eCollection 2021.

Metabolic Syndrome and Breast Cancer: Prevalence, Treatment Response, and Prognosis

Shuwen Dong  1 , Zheng Wang  1 , Kunwei Shen  1 , Xiaosong Chen  1
Affiliations
Review

Metabolic Syndrome and Breast Cancer: Prevalence, Treatment Response, and Prognosis

Shuwen Dong et al. Front Oncol. .

Abstract

Metabolic syndrome is a type of multifactorial metabolic disease with the presence of at least three factors: obesity, diabetes mellitus, low high-density lipoprotein, hypertriglyceridemia, and hypertension. Recent studies have shown that metabolic syndrome and its related components exert a significant impact on the initiation, progression, treatment response, and prognosis of breast cancer. Metabolic abnormalities not only increase the disease risk and aggravate tumor progression but also lead to unfavorable treatment responses and more treatment side effects. Moreover, biochemical reactions caused by the imbalance of these metabolic components affect both the host general state and organ-specific tumor microenvironment, resulting in increased rates of recurrence and mortality. Therefore, this review discusses the recent advances in the association of metabolic syndrome and breast cancer, providing potential novel therapeutic targets and intervention strategies to improve breast cancer outcome.

Keywords: breast cancer; incidence; metabolic syndrome; obesity; prognosis; treatment response.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Metabolic syndrome and its molecular changes related to the risk of breast cancer. Obesity, diabetes, hypertension and dyslipidemia are the main components of metabolic syndrome and are all significantly related to the risk of breast cancer. Obesity increases fibroblasts, T cells, macrophages, leptin, TNF-α, IL-6 and IL-8 and decreases adiponectin. Diabetes is characterized by upregulation of insulin and IGF-1 and downregulation of SHBG and IGFBP. Hypertension is associated with increased ANG II and sodium and decreased calcium. Dyslipidemia leads to high levels of TG, TC, LDL, and VLDL and low levels of HDL. Changes in the expression of these key molecules are correlated with an elevated risk of breast cancer. (‘the blue arrow’ means increase and ‘the red arrow’ means decrease).
Figure 2
Figure 2
The key pathways and molecular mechanisms of components of metabolic syndrome leading to tumor proliferation, invasion and metastasis. (A) The mechanism of obesity and its related key molecules leading to breast cancer with important signaling pathways, including LKB1/AMPK/mTOR, AMPK/ULK, JAK2/STAT3, Ras/Raf/MEK/ERK, NF-κB and PI3K/Akt/mTOR. (B) The mechanism of diabetes mellitus type 2 and its related key molecules leading to breast cancer with important signaling pathways, including PI3K/Akt/mTOR, Ras/Raf/MEK/ERK and NF-κB. (C) The mechanism of hypertension and its related key molecules leading to breast cancer with important signaling pathways, including NF-κB, PI3K/Akt/mTOR and CAM/CAMK/ERK. (D) The mechanism of dyslipidemia and its related key molecules leading to breast cancer with important signaling pathways, including PI3K/Akt/mTOR, JAK2/STAT3 and ERα/STAT3.
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