Role of Lipoproteins in the Pathophysiology of Breast Cancer

Abstract

Breast cancer is one of the most common malignancies in women and the leading cause of cancer mortality. Hypercholesterolemia and obesity are potential risk factors for the incidence of breast cancer, and their detection can enhance cancer prevention. In this paper, we discuss the current state of investigations on the importance of lipoproteins, such as low denisity lipoproteins (LDL) and high density lipoproteins (HDL), and cholesterol transporters in the progression of breast cancer, and the therapeutic strategies to reduce breast cancer mortality. Although some research has been unsuccessful at uncovering links between the roles of lipoproteins and breast cancer risk, major scientific trials have found a straight link between LDL levels and incidence of breast cancer, and an inverse link was found between HDL and breast cancer development. Cholesterol and its transporters were shown to have significant importance in the development of breast cancer in studies on breast cancer cell lines and experimental mice models. Instead of cholesterol, 27-hydroxycholesterol, which is a cholesterol metabolite, is thought to promote propagation and metastasis of estrogen receptor-positive breast cancer cell lines. Alteration of lipoproteins via oxidation and HDL glycation are thought to activate many pathways associated with inflammation, thereby promoting cellular proliferation and migration, leading to metastasis while suppressing apoptosis. Medications that lower cholesterol levels and apolipoprotein A-I mimics have appeared to be possible therapeutic agents for preventing excessive cholesterol’s role in promoting the development of breast cancer.

LDL-C/HDL-C ratio:a strong metabolic risk factor of invasive breast cancer

“…Liu YL et al found that elevated LDL-C levels and an increased LDL-C/HDL-C might favour development of lymph node metastasis and that LDL-C/HDL-C might be a more effective biomarker for identifying advanced N2 stage than LDL-C levels alone in males with colorectal cancer (24). However, two studies from Sweden and France did not conclude association involving LDL-C/HDL-C and BC risk (7,10). This discrepancy may be due to ethnic differences and other various confounding characteristics of the study populations.…”

“…Even though no complete consensus were achieved, major large studies and scienti c trials have found a positive link between LDL-C and BC risk, and a reversed link between HDL-C and BC risk (7)(8)(9)(10). A number of previous studies focused on the role of LDL-C on BC development.…”

“…Although the conclusions of these studies are not completely consistent, metabolically unhealthy is positively associated with total BC and invasive BC risk in most studies (5)(6). Furthermore, although the results remained inconsistent,major scienti c studies have veri ed the positive relevance involving low density lipoprotein cholesterol(LDL-C) and BC risk, and the reversed relevance involving high density lipoprotein cholesterol (HDL-C) and BC risk (7)(8)(9)(10). However, the relevance between LDL-C/HDL-C and BC in women…”

Hypercholesterolemia in Cancer and in Anorexia Nervosa: A Hypothesis for a Crosstalk

“…In this regard, a relation between hypercholesterolemia and inflammation, activated by oxidated lipoproteins, was reported. In fact, the oxidation of LDL is considered to be responsible for the activation of many pathways associated with inflammation in breast cancer [45] and colorectal cancer [46]. Thus, hypercholestrolemia is able to induce a low-grade inflammatory state [47].…”

Clinically Deployable Bioelectronic Sensing Platform for Ultrasensitive Detection of Transferrin in Serum Sample

“…Cancer cells and CSCs need bulk ferritin to survive and proliferate in hypoxic conditions. However, serum Tf undergoes saturation under high ferritin levels, leading to low Tf levels in serum [ 8 ]. It has been observed that with an increase in tumor staging and grading, there would be an enhanced rate of iron metabolism, suggesting that as the tumor grade increases, ferritin levels increase.…”