Cholesterol is a waxy, fat-like substance found throughout the body, including the blood. Total cholesterol consists primarily of high-density lipoprotein (HDL, the "good" cholesterol), low-density lipoprotein (LDL, the "bad" cholesterol), and triglycerides. High circulating cholesterol has been linked to increased risk of breast cancer in women. Normal breast cells respond to LDL by increasing proliferative and pro-inflammatory signaling, thereby setting the stage for breast cancer development. Unfortunately, high HDL levels have also been found to be associated with increased breast cancer risk. Now a new study has reported that high circulating LDL increases tumor growth in mouse models of HER2+ and triple negative (ER-/PR-/HER2-) breast cancer.
Low cholesterol can also be associated with breast cancer
While high cholesterol has been linked to increased risk of breast cancer, the same is also true of low cholesterol. Circulating cholesterol levels have been observed to decline during mammary tumor development in mice, providing evidence of increased use of cholesterol by such tumors. Therefore, low cholesterol can indicate that undiagnosed tumors are already using cholesterol. In fact, some researchers have theorized that breast cancer cells might migrate to seek out cholesterol when their needs are not being met in their local environment. This suggests that drastically reducing circulating cholesterol levels in the absence of other strategies to reduce metastasis could backfire.
Statins and breast cancer
Statin drugs, which are used to treat high cholesterol, have been reported to reduce breast cancer risk in some studies but not in others. Similarly, breast cancer recurrence might be reduced by statin use. However, statin use appears to increase the risk of type 2 diabetes, which is in itself a breast cancer risk factor. As a result, the topic of statin use and its association with breast cancer is not settled. It is not certain which breast cancer survivors should use statins to reduce cholesterol, although there appears to be a clear benefit for inflammatory breast cancer (IBC) patients.
Most women can reduce their cholesterol levels, especially LDL cholesterol, by increasing their level of physical activity and adopting an appropriate diet. In fact, the diets recommended for various types of breast cancer in this website are all cholesterol-lowering. A change in diet and exercise can often quickly start to reduce cholesterol levels. However, some women cannot reduce their cholesterol levels to acceptable levels through diet and exercise alone due to their genetic makeup. For those with breast cancer who need to take statins, lipophilic statins such as Zocor and Lipitor appear to be the best choice.
Latest research finds cholesterol increases HER2+ and TN tumor growth
The study referenced at the beginning of this news story was designed to examine how LDL and LDL receptor expression in tumor cells influence breast cancer growth. To conduct the study, the authors used both newly developed and established mouse models of hyperlipidemia (high levels of lipids (fats) in the blood). The mice were divided into groups to investigate the effects of elevated LDL in HER2+ overexpressing (MCNeuA)— and triple negative (MDA-MB-231)—derived tumors in the animals.
Tumors derived from both HER2+ and triple negative breast cancer cells were found to have elevated LDL receptor expression compared to normal tissue. The tumors grew larger in mice with high circulating LDL compared to mice with lower LDL. Additional experiments demonstrated that silencing the LDL receptor resulted in lower growth of tumors in the HER2+ mouse group. Cell studies also demonstrated that silencing the LDL receptor resulted in reduced cell survival in serum-starved conditions.
The authors also used publicly available data sets to examine the association between high LDL and relapse-free survival among breast cancer patients. They found that high LDL receptor expression in breast cancer was associated with reduced relapse-free survival, especially in patients given systemic treatments. The authors conclude that elevated circulating LDL interacts with the LDL receptor in triple-negative and HER2+ breast cancers to contribute to the increased recurrence and mortality.