New tricks for old drugs – blocking oestrogen to prevent breast cancer

Can drugs like tamoxifen be used to prevent breast cancer?

Tamoxifen is one of the mainstays of breast cancer treatment. Since the early 1980s, it’s been given to women who’ve had breast cancer to try to stop the disease returning.

As a result, it’s saved the lives of millions around the world, and some regard it as the most important cancer drug ever developed.

But today this old drug returns to the spotlight, with a new study showing that tamoxifen and other oestrogen- blocking medicines can reduce the chances of healthy women developing breast cancer.

We’ve blogged before about the discovery of tamoxifen, and Cancer Research UK’s role in its development.

But until now it’s not been clear whether tamoxifen and related drugs might have benefits for healthy women. Today’s finding, by an international team led by Cancer Research UK-funded researchers, provides the best evidence yet that these drugs could be used to help prevent breast cancer in women at average and above-average risk of the disease.

This is hugely significant. If benefits are shown to outweigh the risks, offering women at high risk of breast cancer a drug to lower their risk, could potentially prevent many thousands of breast cancer cases in the UK alone.

Let’s look at their findings, and at what happens next.

How do tamoxifen and its sister drugs work?

Tamoxifen comes from a group of drugs called a ‘selective oestrogen receptor modulators’ or SERMs. These medicines work by interfering with the action of proteins known as oestrogen receptors, and, in doing so, they prevent oestrogen – a hormone – from encouraging cells to divide.

In patients with the most common type of breast cancer – known as oestrogen-receptor positive (ER-positive) breast cancer – tamoxifen can stop tumours in their tracks, preventing them growing.

Since it was discovered, researchers have developed several other SERMs called raloxifene, arzoxifene and lasofoxifene. These are most commonly used to help prevent fractures in women with osteoporosis.

A closer look at the new study

Over the years, several randomised controlled trials (considered the ‘gold standard’ in clinical evidence) have looked at whether taking SERMs can lower a woman’s chance of developing breast cancer.

But often, a single trial – no matter how rigorous – doesn’t provide a definitive answer. So researchers have developed a technique called a ‘meta-analysis’, where the results of several trials can be combined to give an even more concrete answer.

Cancer Research UK’s Professor Jack Cuzick and his colleagues carried out just such an analysis of the results from nine randomised controlled trials of SERMs to prevent breast cancer.

With data stretching over 10 years, from over 80,000 women at average or high risk of breast cancer, they were able to pin down the effects of taking SERMs for five years or longer, compared to with those who did not.

Their results were striking.

Professor Cuzick, who led the research

Women who had taken SERMs had a 38 per cent reduction in risk of breast cancer compared to those who hadn’t.

In other words, if 1000 women took SERMS for five years or longer, and were followed for a further five years, you’d see 21 fewer cases of breast cancer than you would among 1000 women who didn’t take the drugs.

The data also showed that rates of breast cancer were lowest in the first five years (i.e. when women were actually taking the medicines).

But the benefit remained even five years after treatment had ended.

Here’s another way to look at it: for every 42 women who took SERMs, one case of breast cancer was prevented.

While the previous trials suggested that SERMs can reduce the risk of breast cancer in the short term, the new study has a few advantages over its predecessors:

• It includes all SERM trials
• It includes more women
• There’s a longer follow-up time
• It compares four SERMs, where individual trials included only one or two.

Not the whole story

This may all sound too good to be true and, unfortunately, there are indeed some drawbacks. As many who’ve taken tamoxifen for breast cancer will testify, these drugs are not completely harmless.

Again, the meta-analysis allowed these to be compared with the drugs’ benefits. When Cuzick and his colleagues examined the risk of side effects, they found that the risk of blood clots in the veins (including deep vein thrombosis and pulmonary embolism) increased by 73 per cent , while there was also an increased risk of womb (endometrial) cancer in the first five years (although the risk returned to normal after they stopped taking the SERMs).

For every 1000 women taking the drugs for five years, there were 3 extra endometrial cancers, and 6 extra blood clots over the ten year study period (for context, the increased risk of blood clots is similar to that seen with HRT).

Next steps

It’s not every day that affordable, available medicines are shown to cut the risk of a common cancer. Breast cancer affects nearly 50,000 women every year this country, so even a small percentage reduction in overall risk would have a big impact.

This is undoubtedly an exciting piece of research. But it’s not the end of the story.

We now need organisations like the National Institute for Clinical and Health Excellence to fully assess the balance of harms and benefits of these drugs – something they are in the process of doing. With drugs that have significant side effects – and SERMs undoubtedly have side effects – it’s important only to give them to people for whom the benefits outweigh the risks. This needs careful thought and planning.

For example, not everyone has the same risk of breast cancer. We discussed this before in the context of breast screening – targeting healthy women at highest risk would make it more likely the potential risks – a small increase in side effects – would be largely outweighed by the benefits – a large drop in breast cancer risk.

Professor Cuzick estimates that about 5-10 per cent of women in the UK are at the highest risk of breast cancer – about 500,000 women in total. This study raises the tantalising prospect that these women should be offered a SERM.

At Cancer Research UK, we hope that, one day soon, women will be offered SERMs to prevent breast cancer. But there’s still some work to do to find out which women, and which SERM, and under what circumstances.

Hazel

• Hazel Nunn is head of health evidence and information at Cancer Research UK

Reference 

• Cuzick J., Sestak I., Bonanni B., Costantino J.P., Cummings S., DeCensi A., Dowsett M., Forbes J.F., Ford L. & LaCroix A.Z. & (2013). Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data, The Lancet, DOI: 10.1016/S0140-6736(13)60140-3