Abstract
Breast cancer is the most prevalent cancer and primary cause of cancer-related mortality in women. The identification of risk factors can improve prevention of cancer, and obesity and hypercholesterolemia represent potentially modifiable breast cancer risk factors. In the present work, we review the progress to date in research on the potential role of the main cholesterol transporters, low-density and high-density lipoproteins (LDL and HDL), on breast cancer development. Although some studies have failed to find associations between lipoproteins and breast cancer, some large clinical studies have demonstrated a direct association between LDL cholesterol levels and breast cancer risk and an inverse association between HDL cholesterol and breast cancer risk. Research in breast cancer cells and experimental mouse models of breast cancer have demonstrated an important role for cholesterol and its transporters in breast cancer development. Instead of cholesterol, the cholesterol metabolite 27-hydroxycholesterol induces the proliferation of estrogen receptor-positive breast cancer cells and facilitates metastasis. Oxidative modification of the lipoproteins and HDL glycation activate different inflammation-related pathways, thereby enhancing cell proliferation and migration and inhibiting apoptosis. Cholesterol-lowering drugs and apolipoprotein A-I mimetics have emerged as potential therapeutic agents to prevent the deleterious effects of high cholesterol in breast cancer.
Highlights
Breast cancer is the third most common cancer overall, with an estimated incidence of 1.7 million cases in 2016 and a 29% increase in incident cases between 2006 and 2016
We review the progress to date in research on the potential role of the main cholesterol transporters, low-density and high-density lipoproteins (LDL and HDL), on breast cancer development
Some studies have failed to find associations between lipoproteins and breast cancer, some large clinical studies have demonstrated a direct association between LDL cholesterol levels and breast cancer risk and an inverse association between HDL cholesterol and breast cancer risk
Summary
Breast cancer is the third most common cancer overall, with an estimated incidence of 1.7 million cases in 2016 and a 29% increase in incident cases between 2006 and 2016. Cancer cells show specific alterations in different aspects of lipid metabolism, which can affect the availability of structural lipids for the synthesis of membranes, contribution of lipids to energy homeostasis, and lipid signaling functions, including the activation of inflammation-related pathways. The interplay among cholesterol, lipoproteins, proinflammatory signaling pathways, and tumor development has mainly been studied in breast cancer cells and experimental models in vivo. In humans, both benign and malignant proliferation of breast tissue were associated with changes in plasma lipid and lipoprotein levels [8], despite that epidemiological data on the association between lipoproteins and breast cancer showed inconclusive results [9,10,11]. PubMed was searched comprehensively with combinations of the keyword Breast Cancer and the rest of keywords related with cholesterol and lipoproteins
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