Could statins prevent breast cancer returning?

“Statins could be used in the treatment of breast cancer,” Sky News report. Findings from a new study suggest the potential involvement of cholesterol in the recurrence of breast cancer following treatment.

The researchers hope their discovery could pave the way towards new treatment targets, and say that the effect of cholesterol-lowering drugs (such as statins) now needs to be examined. 

The research centred on what is known as oestrogen receptor-positive (or “ER+”) breast cancers – where cancer growth is stimulated by the hormone oestrogen; these account for the majority of cases. Hormonal treatments such as tamoxifen can be used to block the effects of oestrogen. However, in some cases, these cancers build up resistance to the lack of oestrogen and can return. This study aimed to investigate why this happens and suggests that one of the answers may lie in cholesterol.

The findings suggest that specific cholesterol molecules (25-HC and 27-HC) are produced in the absence of oestrogen, which may stimulate further tumour growth. This may be one of the reasons behind cancer resistance.

Current evidence suggests the most effective method for reducing your risk of breast cancer reoccurrence is to follow standard healthy living advice: stop smoking, exercise regularly, eat a healthy diet, maintain a healthy weight and moderate your alcohol consumption.

Where did the story come from?

The study was carried out by researchers from a number of institutions, including the London Institute of Cancer Research, University of Oslo and the Department of Biochemistry, Royal Marsden Hospital in London. It was funded by the Breast Cancer Now Toby Robins Research Centre and NHS Trust funding.

The study was published in the peer-reviewed scientific journal Breast Cancer Research. It is available on an open-access basis and is free to read online here.

The UK media’s headlines are slightly premature by suggesting that the study has already assessed the effect of statins on breast cancer recurrence, which isn’t the case. However, the main body of the news articles were more accurate, with the papers acknowledging that most of the research was in the lab, and therefore has not yet been tested on humans.

What kind of research was this?

This was a laboratory study, which aimed to identify the biological pathways that could be responsible for some oestrogen receptor-positive (ER+) breast cancers becoming resistant to hormone treatments. (“ER” is used due to the American spelling of oestrogen: estrogen).

Eighty percent of breast cancers are reported to carry oestrogen receptors and, while current hormone treatments such as aromatase inhibitors are effective at blocking the action of oestrogen, many patients relapse. Previous research had indicated that cholesterol-producing pathways may be involved. 

Laboratory studies like this are useful early stage research for getting an indication of biological processes and how things work at a cellular level. They can pave the way towards the development of new treatments, or using existing treatments in new ways to treat different diseases. However, clinical trials would need to be conducted to understand whether proposed treatments are firstly safe, and then effective, for this purpose in humans.

What did the research involve?

The researchers aimed to identify novel mechanisms of resistance to oestrogen deprivation. They first cultured five different types of ER+ breast cancer cells. These were grown in the absence of oestrogen until their growth rate was no longer dependent on the hormone.

They then analysed the changes in gene activity and protein production that occurred in this setting of oestrogen deprivation.

On finding increased activity of the cholesterol-producing pathway, they assessed the effect that the cholesterol molecules 25-HC and 27-HC had on cancer cell growth, and also looked at what happened when they interrupted the genes needed to produce them.

They then verified their findings in two cohorts of people with ER+ breast cancer who had been treated with aromatase inhibitors or tamoxifen.

What were the basic results?

Overall, the researchers found that ER+ breast cancer cells grown in the absence of oestrogen show increased activity of cholesterol-producing pathways. The cholesterol molecules 25-HC and 27-HC can mimic oestrogen and stimulate cancer growth instead.

When they interfered with the genes needed to produce these cholesterol molecules using small interfering RNAs (siRNAs – artificially made packets of genetic material), they observed a 30-50% drop in cancer cell growth.

Gene analysis of samples from the cohort of people with ER+ patients who had been treated with aromatase inhibitors showed that poor response to treatment was associated with increased expression of four enzymes that are required to make cholesterol molecules.

How did the researchers interpret the results?

The researchers concluded: “Our observations suggest that enzymes within the cholesterol biosynthesis pathway may be associated with acquired resistance to AI [aromatase inhibitors] therapy. Our study highlights the need to evaluate the lowering of cholesterol on the impact of endocrine therapy.”

Conclusion

The study aimed to identify biological pathways that could be the reason why some ER+ breast cancers relapse after oestrogen-blocking treatment.

It seems that one of the answers for treatment resistance lies in increased activity of cholesterol-producing pathways in the absence of oestrogen. The cholesterol molecules mimic oestrogen and stimulate further tumour growth.

The researchers hope that their research could potentially highlight a new pathway, which could be used as a target for therapeutic treatment in the future. Dr Lesley-Ann Martin from the research team told the media, “This is hugely significant. Testing the patient’s tumour for 25-HC or the enzymes that make it may allow us to predict which patients are likely to develop resistance to hormone therapy, and tailor their treatment accordingly.”

While this may be an important discovery, and could hopefully pave the way to more targeted treatments, the research has so far only been performed in cells in the lab. Cholesterol-blocking treatments such as statins may have new potential in the management of some people with ER+  breast cancers, but they have not yet been tested for this use.

Further laboratory studies are likely to be needed to test the effect of statins upon cancer growth. If these results are positive, this may lead to clinical trials to test whether statins have the same effect in people as they do on cancer cell growth in the lab. This will identify which women could benefit from statin involvement in their breast cancer treatment, and to see if there are any long-term side effects.

Current evidence suggests that the most effective methods to reduce your risk of breast cancer reoccurrence is to follow standard healthy living advice: stop smoking, exercise regularly, eat a healthy diet, maintain a healthy weight and moderate your alcohol consumption.

Links To The Headlines

Statins Could Stop Breast Cancer Return – Study. Sky News, June 1 2016

Statins ‘could be valuable addition to breast cancer treatment’. The Guardian, June 1 2016

Statins could prevent breast cancer returning, study suggests. The Daily Telegraph, June 1 2016

Statins could provide hope for millions of breast cancer sufferers. Daily Mirror, June 1 2016

Statins offer new way to beat breast cancer – for good. The Times, June 1 2016 (subscription required)

Links To Science

Simigdala N, Gao Q, Pancholi S, Roberg-Larsen H, et al. Cholesterol biosynthesis pathway as a novel mechanism of resistance to estrogen deprivation in estrogen receptor-positive breast cancer. Breast Cancer Research. Published online June 1 2016