Hypercholesterolemia and Breast Cancer

It has been clearly established that obesity and the metabolic syndrome are risk factors for estrogen receptor (ER) positive breast cancer – a type of breast cancer in which the tumor cells bind the female hormone estrogen – in postmenopausal women.

This increased risk has been attributed to a number of factors including:

• Increased levels of insulin and insulin-like substances in the circulation
• Localized production of estrogen in adipose (fat) tissues
• The role of inflammatory substances like cytokines in enhancing tumor cell growth.

Recent studies have implicated hypercholesterolemia – high levels of cholesterol in the bloodstream – as a definitive risk factor in for estrogen receptor (ER) positive breast cancer in postmenopausal women.  Hypercholesterolemia correlates with obesity and together these conditions have been shown to increase morbidity.  In addition, it has been shown that disease-free survival is improved in those patients who were taking statins prior to diagnosis.  Statins are members of  a class of compounds designed to inhibit cholesterol production in the liver

Although it has been proposed that statins exert their effect by directly inhibiting tumor cell growth, the amount of circulating statins in individuals who use the drug at the typical dose level is far below the amount required to inhibit cancer cell growth as has been reported in–vitro  (in the laboratory).  Therefore, there must be some other explanation.  An understanding of the role of cholesterol in breast cancer pathology would be invaluable in regards to possible therapeutic approaches.  Dr. Eric R. Nelson and his colleagues from the Department of Pharmacology and Cancer Biology at the Duke Institute for Genome Sciences and Policy at Duke University in Durham, NC, have made a significant contribution in this regard.

Nelson and his group have shown that the actual substance that seems to be responsible for accelerating the growth of breast cancer tumors is a metabolite of cholesterol – 27-Hydoxycholesterol (27HC).  Furthermore, 27HC is a product of the action of the enzyme cytochrome P450 oxidase (CYP27A1).   The expressed level of CYP27A1 correlates well with tumor grade in breast cancer patients and inhibition of this enzyme had a positive impact on the suppression of tumor growth.

 

From this data, the authors conclude that lowering the level of circulating cholesterol or inhibiting its conversion to 27HC represent effective strategies in the treatment of estrogen receptor (ER) positive breast cancer in postmenopausal women.  This is, indeed, an important finding.