The Role of HDL in Breast Cancer: Insights with Avanti Research’s Deuterium-Labeled Oxysterols

Breast cancer – one of the most prevalent cancers in the world – has been researched for many years with regards to lipid metabolism. Specifically, how HDLc impacts the development of breast cancer has attracted major interest. This blog discusses an article in Scientific Reports on plasma lipids and breast cancer, focusing particularly on the HDL function. Most central to this work is the availability of deuterium-labeled oxysterols (sourced from Avanti Research), which allowed them to measure oxysterol content in isolated HDL samples.

Products from Avanti Research were key players in this research, providing the deuterium-labelled oxysterols for GC-MS analysis. They were labelled as 7α-hydroxycholesterol-d7, 7β-hydroxycholesterol-d7, 25-hydroxycholesterol-d6, and 27-hydroxycholesterol-d6 internal controls for quantifying oxysterols in the HDL samples. Internal standards are a staple of analytical chemistry since they facilitate precise standardization of sample data.

With Avanti’s lipids, the researchers could pinpoint the concentration of each oxysterol in breast cancer patients’ HDL. This finding was fundamental to the study’s success because it revealed significant correlations between oxysterol levels, HDL function and breast cancer progression.

The Major Findings from the Study:

1. Increased Plasma Lipids in Triple-Negative Breast Cancer: TN breast cancer patients had elevated plasma lipids, including total cholesterol (TC), triglycerides (TG), apolipoprotein B (apoB), and non-HDL cholesterol (non-HDLc), when compared with other forms of breast cancer. This suggests that lipid metabolism could be firmly connected to TN breast cancer’s aggressiveness.

2. HDL Composition and Activity: While breast cancer patients had lower concentrations of certain lipids (TC, phospholipids, TG, and 27-hydroxycholesterol) compared with control, HDL performed comparable in allowing cholesterol efflux, the flushing out of cells, of cholesterol. That observation suggests that HDL function, not only HDLc, is more relevant to the prognosis of breast cancer.

3. HDL Function in Advanced-Stage Cancer: For advanced-stage patients with breast cancer, the researchers detected low HDL function. Though similar in lipid composition to early patients, HDL from late patients did not have as much impact on expelling cholesterol from macrophages. This compromised functionality might be part of what drives the disease.

These data suggest that the way in which HDL clears cholesterol from cells (rather than its cholesterol levels) might be important in the development of breast cancer. The granular quantification of oxysterols by Avanti’s lipids helped to reveal these subtle links between HDL and breast cancer.

HDL Functioning as an Explicit Therapeutic Area.

While the article doesn’t specifically recommend novel therapies, it does suggest that HDL function might be a key target for the development of breast cancer treatments in the future. The reasons are a few, but here are some:

1. Decreased HDL Function in Late Stage Breast Cancer: The study reported that late stage (stage III, IV) women had impaired HDL function, despite the similar HDL levels of lipids and apolipoprotein A-I as those earlier patients. This deficit might be associated with breast cancer progression and HDL function could be a target for therapy.

2. Cholesterol Efflux and Tumor Microenvironment: HDL participates in the process of reverse cholesterol transport (excess cholesterol is removed from cells). When we have cancer, cholesterol accumulation makes the tumour grow. According to the study, HDL in cholesterol efflux could play an important role in regulating cholesterol within tumor cells and may even be involved in the spread of cancer.

3. Potential Therapeutic Targeting and Enhancement of HDL Function – in particular its ability to filter out cholesterol from cancer cells – will provide exciting opportunities for the treatment of breast cancer. But there’s still work to be done on how dysfunctional HDL function happens, and how it can be harnessed for therapeutic purpose.

What We Need to Think About for the Next Research.

1. Mechanisms of Loss of HDL Function: Finding biological reasons for loss of HDL function in breast cancer may hold the promise of specific treatments that will increase HDL function in cancer patients.

2. HDL as a Moving Picture: The paper poses a challenge to the idea of HDL as a fixed marker using HDLc values. Rather, HDL can be understood as an evolving system whose activity can be modulated by various conditions in the tumor microenvironment.

3. Focus on Function, Not Just Levels: Future research may look more closely at HDL function rather than HDLc levels as an endpoint for cardiovascular and cancer risk factors. Such a reorientation may produce more precise biomarkers and cancer treatments for breast cancer.

Conclusion

Its findings shed new light on the correlation between HDL activity and breast cancer, providing a new way to look at lipids in cancer biology. Avanti Research’s deuterium-labeled oxysterols were essential to the study’s ability to accurately measure oxysterols, and they could provide vital information about the dysfunctional HDL of advanced breast cancer patients. While much has yet to be found, HDL function as a target for therapy is still a potentially exciting field for future breast cancer research.

Be sure to check out all of Avanti Research's deuterated sterols for all of your research needs!

For the full research article, click here: Sawada, M.I.B.A.C., de Fátima Mello Santana, M., Reis, M. et al. Increased plasma lipids in triple-negative breast cancer and impairment in HDL functionality in advanced stages of tumors. Sci Rep 13, 8998 (2023). https://doi.org/10.1038/s41598...