HDL and LDL: Potential New Players in Breast Cancer Development

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.

Download Full-text

The Mechanism of Lunasin's Effect on the Growth of Breast Cancer Cells Induced by Obesity-induced Inflammation

Impact ◽

10.21820/23987073.2020.7.16 ◽

2020 ◽

Vol 2020 (7) ◽

pp. 16-18

Author(s):

Chia-Chien Hsieh

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Inflammatory Responses ◽

Specific Area ◽

Tumour Microenvironment ◽

Associate Professor ◽

World Health ◽

Cancer Development ◽

Breast Cancer Development

It has long been established that diet and nutrition can have a significant impact on health and even help reduce the prevalence of chronic diseases. It makes sense that what we put into our bodies would have some bearing on how our bodies function. Indeed, the World Health Organization developed guidelines focusing on nutrient intake, with a view to reducing the global burden of disease related to obesity, diabetes, cardiovascular disease, several forms of cancer, osteoporosis and dental disease. One exciting area of research, that is little understood, is the potential efficacy of lunasin – a peptide found in soy, legume and some cereal grains – against certain types of cancer. Lunasin has shown potential in the prevention of cancers. It is able to do this by suppressing the proliferation and migration of cancer cells, and anti-inflammation in this tumour environment. A specific area of study within this is lunasin's ability to reduce obesity associated breast cancer development. Associate Professor Chia-Chien Hsieh, a researcher based at the Programs of Nutrition Science, School of Life Science, National Taiwan Normal University, current work is focused on the mechanism of lunasin's effect on the growth of breast cancer cells induced by obesity-associated inflammation. Her goal is to investigate the obesity-related breast cancer chemoprevention of lunasin, which might retard inflammatory responses around tumour microenvironment and even break the crosstalk of macrophages, adipocyte, and breast cancer cells. The aim being to provide potential strategies for ameliorating obesity-related ER(+) or ER(-) breast cancer development.

Download Full-text

rs10514231 Leads to Breast Cancer Predisposition by Altering ATP6AP1L Gene Expression

Cancers ◽

10.3390/cancers13153752 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3752

Author(s):

Shumin Ma ◽

Naixia Ren ◽

Qilai Huang

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Target Identification ◽

Migration And Invasion ◽

Regulatory Activity ◽

Breast Cancer Predisposition ◽

Gene Assay

Numerous genetic variants located in autophagy-related genes have been identified for association with various cancer risks, but the biological mechanisms underlying these associations remain largely unknown. Here we investigated their regulatory activity with a parallel reporter gene assay system in breast cancer cells and identified multiple regulatory SNP sites, including rs10514231. It was located in the second intron of ATG10 and showed gene regulatory activity in most breast cancer cells we used. Mechanistically, the T allele of rs10514231 led to ATP6AP1L downregulation by decreasing the binding affinity of TCF7L2. Overexpression of the ATP6AP1L gene in cancer cells diminished cell proliferation, migration, and invasion. Notably, ATP6AP1L downregulation correlated with breast cancer risk and with poor prognosis in patients. These results provide a plausible mechanism behind the association of rs10514231 with breast cancer risk and will be important for more effective therapeutic target identification for precision medicine.

Download Full-text

Evaluation of the Tyrer-Cuzick (International Breast Cancer Intervention Study) Model for Breast Cancer Risk Prediction in Women With Atypical Hyperplasia

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.0784 ◽

2010 ◽

Vol 28 (22) ◽

pp. 3591-3596 ◽

Cited By ~ 65

Author(s):

Judy C. Boughey ◽

Lynn C. Hartmann ◽

Stephanie S. Anderson ◽

Amy C. Degnim ◽

Robert A. Vierkant ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Invasive Breast Cancer ◽

Atypical Hyperplasia ◽

Cancer Development ◽

Cancer Risk Assessment ◽

Individual Risk ◽

Breast Cancer Development ◽

Breast Cancer Risk Assessment

Purpose Accurate breast cancer risk assessment is vital to personalize screening and risk reduction strategies. Women with atypical hyperplasia have a four-fold higher risk of breast cancer. We evaluated the performance of the Tyrer-Cuzick model, which was designed to predict 10-year risk of breast cancer development, in a well-defined cohort of women with atypia. Patients and Methods The Mayo Benign Breast Disease cohort includes 9,376 women who had a benign breast biopsy between 1967 and 1991. Among those, 331 women with atypia were identified by our study pathologists. Risk factor data for the Tyrer-Cuzick model were collated for each woman and used to predict individual risk of developing invasive breast cancer within 10 years. Results Over a median follow-up of 14.6 years, 64 (19%) of the 331 women developed invasive breast cancer. In the first 10 years after biopsy, 31 women developed invasive breast cancer whereas the Tyrer-Cuzick model predicted 58.9. The observed-to-predicted ratio was 0.53 (95% CI, 0.37 to 0.75). The concordance statistic was 0.540, revealing that the Tyrer-Cuzick model did not accurately distinguish, on an individual level, between women who developed invasive breast cancer and those who did not. Conclusion The Tyrer-Cuzick model significantly overestimated risk of breast cancer for women with atypia, and individual risk estimates showed poor concordance between predicted risk and invasive breast cancer development. Thus, we cannot recommend the use of the Tyrer-Cuzick model to predict 10-year breast cancer risk in women with atypical hyperplasia.

Download Full-text

Influence of Breast Reduction Surgery on Long-Term Breast Cancer Risk in Austria

Breast Care ◽

10.1159/000517816 ◽

2021 ◽

pp. 1-5

Author(s):

Albert Niepel ◽

Sven Schwake ◽

Mira Zeichmann ◽

Ariel Noltze ◽

Viktoria König ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Incidence Rate ◽

Breast Reduction ◽

Cancer Development ◽

Control Group ◽

Breast Reduction Surgery ◽

Female Population ◽

Breast Cancer Development

Introduction: Breast reduction surgery is one of the most frequently performed surgeries amongst plastic and reconstructive surgeons worldwide. Previous studies have shown decreased risk of breast cancer development in women undergoing breast reduction surgery of up to 28%. We aimed to evaluate the relative risk of breast cancer development in our patients after breast reduction surgery in relation to the general female population of Austria. Methods: A total of 637 women underwent breast reduction surgery between 2003 and 2017 at our department. From those women, 513 patients completed a follow-up assessment of breast cancer development and were included into the study sample. The age-specific incidence rate data of the general female population of Austria served as the control group and basis for the calculation of the standardized incidence ratio (SIR) and Poisson test. Results: Relative to 5.66 expected cases of breast cancer, our cohort showed 1 subject with breast cancer after breast reduction surgery (SIR = 0.1765). An exact Poisson test was carried out to determine the level of significance of the difference between the incidence rate observed in the sample compared to the expected rate based on the age-specific incidence rates of the general population (p = 0.023, α = 0.05). Discussion: Our study underlines the strong evidence of previous studies for significant breast cancer reduction in patients after reductive mammoplasty. In comparison to the general female population of Austria, our cohort showed a reduction in breast cancer incidence of about 82%. The authors believe that different techniques in reduction mammoplasty have different levels of safety regarding the prevention and risk reduction for breast cancer. Further investigation must be conducted to evaluate the reduction of breast cancer risk with different surgical techniques.

Download Full-text

LEP (−2548G>A LEP) and LEPR (223Gln>Arg, 109Lys>Arg) polymorphisms as breast cancer risk factors in the Polish female population

Molecular Biology Reports ◽

10.1007/s11033-021-06328-7 ◽

2021 ◽

Author(s):

Hanna Hołysz ◽

Anna Paszel-Jaworska ◽

Aleksandra Romaniuk-Drapała ◽

Sylwia Grodecka-Gazdecka ◽

Błażej Rubiś

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Progesterone Receptor ◽

Cancer Development ◽

Neoplastic Disease ◽

Wild Type ◽

Female Population ◽

Breast Cancer Development ◽

Her2 Breast Cancer

AbstractOn a global scale, breast cancer is the most common type of cancer in women, and it is still a growing problem. Therefore, new prognostic or diagnostic markers are required that would facilitate the assessment of patients or provide more efficient therapy, respectively. In these studies, we analyzed the contribution of LEP (2548G>A) and LEPR (109 Lys>Arg and 223Gln>Arg) genes polymorphisms to the risk of breast cancer development. The study involved 209 women aged 59.6 ± 11 years diagnosed with breast cancer and 202 healthy women aged 57.8 ± 8.2 years, who were blood donors. Polymorphism were evaluated by PCR–RFLP reaction followed by the verification of part of the samples by sequencing. The results of the study confirmed obesity as a significant breast cancer development risk factor in Polish women. However, no significant association between the studied polymorphisms and breast cancer risk or severity of the neoplastic disease was found. Interestingly, it was shown that wild type 223Gln>Gln leptin receptor (LEPR) was statistically more common in women with human epidermal growth factor receptor 2 negative (HER2−) than human epidermal groth factor receptor 2 positive (HER2+) breast cancer and wild type form of 2548G>A LEP was more common in women with progesterone receptor positive (PR+) than progesterone receptor negative (PR−) breast cancer. Studied polymorphisms of the LEP and LEPR genes do not increase breast cancer risk in the population of Polish women. However, they can affect PR an HER receptors expression and thus the severity of the disease. Noteworthy, this interesting correlation is being reported for the first time and might constitute an essential contribution to the identification of molecular mechanisms of carcinogenesis.

Download Full-text

Nicotine Synergizes with High-Fat Diet to Induce an Anti-Inflammatory Microenvironment to Promote Breast Tumor Growth

Mediators of Inflammation ◽

10.1155/2020/5239419 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Thalia Jimenez ◽

Theodore Friedman ◽

Jaydutt Vadgama ◽

Vineeta Singh ◽

Alexandria Tucker ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Breast Tumor ◽

High Fat Diet ◽

Breast Cancer Cells ◽

Cancer Development ◽

High Fat ◽

Breast Cancer Development ◽

Anti Inflammatory

Breast cancer results from a complex interplay of genetics and environment that alters immune and inflammatory systems to promote tumorigenesis. Obesity and cigarette smoking are well-known risk factors associated breast cancer development. Nicotine known to decrease inflammatory signals also modulates immune responses that favor breast cancer development. However, the mechanisms by which nicotine and obesity contribute to breast cancer remain poorly understood. In this study, we examined potential mechanisms by which nicotine (NIC) and high-fat diet (HFD) promote growth of HCC70 and HCC1806 xenografts from African American (AA) triple negative (TN) breast cancer cells. Immunodeficient mice fed on HFD and treated with NIC generated larger HCC70 and HCC1806 tumors when compared to NIC or HFD alone. Increased xenograft growth in the presence of NIC and HFD was accompanied by higher levels of tissue-resident macrophage markers and anti-inflammatory cytokines including IL4, IL13, and IL10. We further validated the involvement of these players by in vitro and ex vivo experiments. We found a proinflammatory milieu with increased expression of IL6 and IL12 in xenografts with HFD. In addition, nicotine or nicotine plus HFD increased a subset of mammary cancer stem cells (MCSCs) and key adipose browning markers CD137 and TMEM26. Interestingly, there was upregulation of stress-induced pp38 MAPK and pERK1/2 in xenografts exposed to HFD alone or nicotine plus HFD. Scratch-wound assay showed marked reduction in proliferation/migration of nicotine and palmitate-treated breast cancer cells with mecamylamine (MEC), a nicotine acetylcholine receptor (nAchR) antagonist. Furthermore, xenograft development in immune-deficient mice, fed HFD plus nicotine, was reduced upon cotreatment with MEC and SB 203580, a pp38MAPK inhibitor. Our study demonstrates the presence of nicotine and HFD in facilitating an anti-inflammatory tumor microenvironment that influences breast tumor growth. This study also shows potential efficacy of combination therapy in obese breast cancer patients who smoke.

Download Full-text