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Let's beat cancer sooner

A breast cancer cell (image courtesy of our London Research Institute EM Unit)

The tantalising possibility that breast cancer could be prevented by taking a pill is something our scientists have been exploring since the 1980s. In June this became a reality for some, with NICE recommending tamoxifen and raloxifene for preventing breast cancer in women at increased risk of the disease.

But taking drugs to prevent cancer only makes sense if the benefits outweigh the added risks. And although there are undoubted benefits of tamoxifen – stopping some women from getting breast cancer – it can also have some serious side effects like increased risk of blood clots.

That’s why we’re excited by new results announced today from one of our trials, which suggest that another drug used to treat breast cancer called anastrozole could be even better at preventing the disease than tamoxifen for some women, and also leads to fewer serious side effects.

Women who took anastrozole every day for five years halved their risk of developing breast cancer. This by itself is promising. But there is another benefit too. Women who took anastrozole were only slightly more likely to develop side effects like moderate joint pain than women who took a placebo ‘sugar pill’.

We’re keen to see how the risks and benefits balance in the long-term, but these results look really positive.

Let’s explore more about this possible new option for preventing breast cancer and which women might benefit from taking anastrozole.

Anastrozole and tamoxifen: different paths to the same goal

First though, let’s look at how anastrozole works. The hormone oestrogen fuels the growth of many breast cancers. After women go through the menopause, their oestrogen is no longer produced by the ovaries – instead it’s made by an enzyme called aromatase. Aromatase is found in fatty tissues (such as the breasts), muscle and the skin.

Anastrozole is a type of drug called an aromatase inhibitor. It blocks the action of aromatase and so lowers the amount of oestrogen in post-menopausal women. There are two other aromatase inhibitor drugs used to treat breast cancer, exemestane and letrozole. Exemestane has already shown promising results for preventing breast cancer and letrozole is also being investigated.

Tamoxifen is one of the most effective breast cancer treatments ever developed. It also works by blocking the action of oestrogen but does this in a different way. While anastrozole stops the production of the hormone, tamoxifen stops the oestrogen attaching to breast cancer cells. So oestrogen is still found in the body but its activity is blocked. This type of therapy is called selective oestrogen receptor modulators or SERMs.


Anastrozole can only be used for women who have gone through menopause

Because of these different actions in the body, either tamoxifen or anastrozole are used depending on what stage in life a woman has reached. Anastrozole can only be used for women who have gone through menopause but tamoxifen can be used in both pre- and post-menopausal women.

Which women are considered at high risk?

Breast cancer is the most common cancer in the UK, affecting around 50,000 women every year.

Some women are at higher risk of getting the disease, usually if they have a number of relatives with breast cancer, have had certain types of benign breast disease or have a high breast density.

This new study investigated whether anastrozole could be used to prevent breast cancer in post-menopausal women who have a higher than average risk of developing the disease.

In this trial, women had twice the risk of breast cancer compared to the general population.

The results

Almost 4,000 post-menopausal women took part in the trial and were given either anastrozole or a placebo for five years. In those who took anastrozole, the risk of breast cancer dropped by a huge 53 per cent – the infographic below shows the key numbers from the study:

Anastrozole study findings

To look at this another way, over seven years, 36 women needed to take anastrozole regularly to prevent one case of breast cancer.

Positive balance of benefits and risks

This treatment is not free from side effects. But between the anastrozole and placebo groups the risks seemed to be similar. There was an increase in the number of patients who experienced joint pain and hot flushes/night sweats, but there were no more serious events, such as heart attacks or fractures, compared to the placebo group.

By contrast, tamoxifen raises the risk of blood clots and endometrial cancer.

There have been concerns about whether aromatase inhibitors could reduce bone density – we’ve written before about how another aromatase inhibitor, exemestane, was linked to weakening of the bones.

In this new study, women with severe osteoporosis were excluded and all women had their bone density measured at the start of the trial – anyone at risk was given bone-strengthening drugs called bisphosponhates to prevent bone density problems.

After five years, the number of bone fractures was the same in the group of women treated with anastrozole as those treated with the placebo. So it seems that it’s possible to manage the impact of this drug on women’s bones.

An interesting surprise

A particularly interesting finding in this study was that women who took anastrozole had a lower chance of getting other types of cancer too. Overall, the risk of developing other types of cancer was reduced by 42 per cent.

There were 70 cases of other cancers in the placebo group and only 40 in the women taking anastrozole. In particular skin cancer and bowel cancer were significantly less common.

This result was unexpected and will need further investigation, as it’s not clear why this could be happening. The women in this trial will be followed for a number of years and this will be important to fully understand the long-term side effects and also shed light on other possible benefits such as this.

How does this compare to tamoxifen?

Although the drugs have not been compared directly in a single trial, we can explore the relative risks and benefits:

Tamoxifen Anastrozole
Trial IBIS I: 7145 women, aged 35-70 years and at increased risk of breast cancer received either tamoxifen or placebo for 5 years. IBIS II: 3864 post-menopausal women, aged 40–70 and at increased risk of breast cancer received either anastrozole or placebo for 5 years.
Who Both pre- and post-menopausal women at higher risk of breast cancer. Only post-menopausal women at higher risk of breast cancer.
Benefits 27 per cent reduction in risk of breast cancer. 53 per cent reduction in risk of breast cancer.
Risks Increased likelihood of suffering from blood clots and endometrial cancer, as well as gynaecological side effects (e.g. abnormal bleeding/discharge), and hot flashes/night sweats. Increased likelihood of suffering from joint pain and hot flashes/night sweats. No increased risk of serious events.
Follow up Average 8 years, maximum 10 years
Includes time period after treatment finished, which showed that the side effects were only seen during treatment, but the benefit continued for up to 10 years.
Average 5 years. Longer-term follow up not available yet.

What next?

The burden of breast cancer in the UK is huge. We’re funding a wide range of trials into how we can best treat this devastating disease. But it’s just as important to try to stop women getting breast cancer in the first place.

We already know that there are a number of things women can do to lower their risk of breast cancer such as keeping a healthy weight, being physically active and limiting their alcohol intake. For postmenopausal women with a higher than average chance of developing breast cancer, it’s great news that there’s potentially something else they can do to help cut down the risk.

We feel these results are strong enough for National Institute of Clinical Excellence (NICE) to consider adding anastrozole to their recommendations for breast cancer prevention, along with tamoxifen and raloxifene.

Each of these drugs has a slightly different range of side-effects and is suited to different types of women, so having more drugs on offer will allow doctors to recommend what’s most appropriate for each woman.

In the meantime, we’d like to encourage women who think they might be at high risk of breast cancer to make an appointment with their GP to discuss what might be the best path for them to lower their risk.

Nikki Smith, Health Information Officer

Image of anastrozole packaging from Wikimedia Commons


Maggie Cline May 7, 2014

Stage 1 adenocarcinoma 1/2008, lumpectomy, mammosite radiation and ACT chemo. Started on Arimidex but could not tolerate the severe joint and bone pain. Switched to Femara (letrozole) 2 mg/daily and could not tolerate severe joint and bone pain. Started seeing a rheumatologist whose own mother had been treated for breast cancer and subsequently put on aromatase inhibitors. When the side effects are severe, they are severe and intolerable. Quality of life is extremely poor. She understood all of this from watching her mother go through this treatment and she had to make a medical decision to remove her mother from these drugs. I considered it but decided to try to stick it out for the five years that were recommended at that time. It took 3 muscle relaxants/day, two large doses of NSAIDS/day, two large doses of CoQ10/day and my life was tolerable. I did stop this medication twice for a total period of a year so I actually was on it for six years (with two six month hiatuses). I have been informed that the studies indicate that I should probably stay on it for life, but I cannot contemplate that possibility at this time when I am only off the medication for a little over a month. The problem is that all the other medication I was taking to help with those side effects are causing liver issues and I have to get off them. For me, it’s a trade off–prevent cancer or live a life of excruciating pain and immobility. I’m going to reexamine this at the six month anniversary and decide at that time if I can tolerate taking this drug again. As I said, when a patient has side effects that are not “moderate” (which is how it was described to me prior to taking it), those side effects are severe and life-altering. It’s a dilemma I wish I had the answer to.