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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

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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.

david favre March 20, 2014

Attn: Martin Ledwick; My wife is 70. She had a lumpectomy followed by radiotherapy 5 years ago (2 lymph nodes were OK). She was put on FEMARA tablets but found the leg/joint pains severe. She was switched to ANTASTROZOLE (ARIMIDEX). These have had less side effects but still bad. She takes paracetamol/codine almost daily to easy pain and takes joint supplements. From a fit person she now has difficulty standing/walking for any period. She has now reached 4.5 years on the scheduled 5 year term on the tablets. When switching from FEMARA to ANASTROZOLE the doctor recommended a break in tablets for around a month between stopping “old” and starting “new” and in that time my wife’s pains reduced and mobility improved. We are considering a long holiday (21 days) to celebrate our joint 70ths and wondered if there was any research/information/advice with regard to stopping the ANASTROZOLE for say a month before and during the holiday (say 2 months in all) to help her enjoy the break more. She would then plan to start them again till then end of term and seek advice from her doctor concerning the future. Is there any information/advice on stop/start approach?

Kathy Lopez March 1, 2014

Very informative. I’m a breast cancer survivor for 2 years. My friend who was diagnosed at the same time I was, was just diagnosed with pancreatic cancer. So of coarse my mind started wondering. This article set my mind at ease. Thank you, Kathy Lopez

IBCR February 25, 2014

Wow.. really useful informative blog on breast cancer prevention. We are researching and collecting IBCR repositories with different people experiences. You can visit us at IBCR.

Lesley Asque February 11, 2014

I took part in trials of Tamoxifen and Letrozole about 10 years ago and I had the opportunity to continue taking either one. I have been taking Letrozole for 10 years now I do have side effects, Osteoporosis in my spine and am taking bisphosponhates which seem to be having a positive holding effect. I also suffer from regular urinary track infections and I also continue to have hot flushes and night sweats. But I really believe that taking Letrozole is preventing cancer returning in the other breast and metastases, so hopefully I will continue taking it as long as possible

Theresa January 13, 2014

Hi, have been taking Letrozole daily since August 2011 after right breast mastectomy and
sentinel lymph node biopsy. HER2 neg. ER positive 8/8. When will we have results on
research into Letrozole. No side effects so far, travelling hopefully!

Pat Church January 13, 2014

In 2000 I had a lumpectomy and several lymph glands removed followed by radiotherapy. I was given tamoxifen for 5 years. 2years later the cancer returned and I had another lumpectomy on the other breast. So in 2007 I was given anastrasole. I do not want to come off this as am worried that the breast cancer will return. I have suffered from joint pains but was recommended I take Glucosame, Chondroitin but with MSM which I do and the joints are ok. I am going to insist I keep taking anastrasole as I have also had a full hysterectomy.

Martin Ledwick January 10, 2014

Hi Caroline
At the moment Anastrozole would usually be prescribed for 5 years following other treatments for early breast cancer. But a specialist may sometimes suggest taking it for longer in some circumstances. A study looking at taking a different type of hormonal treatment called Tamoxifen that was recently completed suggested that there may be an advantage in taking this drug for 10 years rather than 5, but similar studies have not yet been done looking at aromatase inhibitors. And it is always important to balance any longer term side effects of treatment with potential benefits. If you have concerns talk them through with your specialist.

Martin Ledwick, Head Information Nurse, Cancer Research UK

Martin Ledwick January 10, 2014

Hi Wendy
So far the studies on using Anastrozole to prevent breast cancer in women who haven’t been diagnosed but are considered to be at high risk have only looked at giving it for 5 years. As these women have never had breast cancer (and may never get it) but are at increased risk, the researchers have to be particularly careful to avoid any long term side effects of it that may outweigh any benefits. At the moment the women in the trial have only been followed up on average for 5 years following completing the course of treatment, so it is not yet known if the increased risk returns after 5 years have elapsed. However, a similar study using a different hormonal treatment called Tamoxifen seemed to have a benefit that lasted for 10 years following completeion of 5 years treatment, so it is quite possible that the benefits last longer than the course of treatment.

In women who are taking Anastrozole to stop a recurrence of breast cancer after being diagnosed with it, the current recommendation is also 5 years, but this may change as more research evidence becomes available.

Martin Ledwick, Head Information Nurse, Cancer Research UK

Martin Ledwick January 10, 2014

Hi Heather
At the moment, for early breast cancer (breast cancer that has not spread to other parts of the body) Anastrozole is usually prescribed for 5 years, but in some circumstances your specialist may opt to carry it on for longer.
In your situation this may have been because you were younger when the cancer first developed and quite a number of your lymph nodes were affected. As more research is done it is possible that guidance may change on how long to take it for, but at the moment for cancers that have not spread there is not yet any clear evidence of benefit of taking it long term. As there can be longer term side effects for taking Anastrozole your specialist would need to balance the risks of taking it for longer against potential benefits which at the moment may not be known. If you have any further questions it may help to give our nurse team a call on freephone 0808 800 4040.

Martin Ledwick, Head Information Nurse, Cancer Research UK

Martin Ledwick January 10, 2014

Hi Alice Heffernan
Generally, if a breast tumour is considered hormone receptor negative, treatments which prevent the action of hormones on the tumour like Tamoxifen and Anastrozole are not thought to be as effective. But, if your cancer ever did recur, or you developed a new breast cancer, your doctors might reassess the situation to see if hormonal treatments might be useful.

Martin Ledwick, Head Information Nurse, Cancer Research UK

Judith Milner January 10, 2014

I had a bi-lateral mastectomy, Grade 3 and 10 positive lymph nodes removed in 2003. Six months of chemotherapy (Taxol) and radiotherapy. Two years on Tamoxifen then was changed to Anastrozole. My oncologist has agreed to me taking Anastrozole indefinitely as I was a high risk cancer patient. Although there are no statistics for people who have taken Anastrozole for this length of time I am prepared to take the risk as I hope this will prevent a recurrence. Suffer some joint pain particularly in the feet.


Heather January 10, 2014

I have been taking anastozole for 7 years previously taken Tamoxifen for 5 years, Was diagnosed with breast cancer stage 3 at age 38 with DCIS -and had tumour 2.5cm with 27 lymph nodes affected had mastectomy followed by 8 months chemo and 8 weeks radiotherapy. Would it be beneficial to stay on Anastrozole I have been told now to stop. Experienced minimal side effects hot flushes and slight joint pain. My consultant thinks it best to stop now was wondering would it be best to continue to stop any re-occurrence.

Wendy January 9, 2014

But what happens after 5 years when you stop taking the pills? Are you at less risk or back to how you were at the beginning? No one seems to know.

Caroline January 9, 2014

I finished taking Anastozole last year after a 5 year period following treatment for Breast Cancer. I had a Lumpectomy, Chemotherapy and Radiotherapy. I did suffer with dreadful night sweats and Hot Flushes but managed to cope ok. I was wondering if it would be beneficially to continue with this treatment to avoid a possible re-occurence? I do have a Family History and both myself and my sister were 42 and 44 when diagnosed.

Kay Lay January 9, 2014

This is very exciting, I’m on anastozole for five years following breast cancer. I have 2 more years to go. However, I get horrible side effects such as burning hot flushes and sweats which come with pounding heart and head, osteoporosis, very aching bones and muscle, severe insomnia and have had to cut my work hours to 16 per week through lack of stamina, I am 60 but am greatful that hopefully this drug will cut my chance of cancer coming back.

Diana Apps January 9, 2014

I was diagnosed with Breast cancer in October 2012 and have received surgery (lumpectomy and removal of two lymph nodes) followed by radiotherapy. I took anastrazole and had joint pains and dental pain, I was switched to tamoxifen and had nausea and psychological side effects and finally I too exemestane which also gave me joint pains, nausea and psychological problems. With the consent of my oncologist, I am no longer taking medication. However, my existing gum disease has progressed to a serious extent and I have just had to have dental surgery prior to implants which was not required prior to the hormome treatment. My dentist, who is an experienced implant surgeon stated that he had not seen any bone disease as bad as mine. This does not appear to be a recognised side-effect but I do know that, within 48 hours of stopping the exemestane, the dental pain resolved, although obviously, the damage had already been done. I also had a number of epuli on my gums which have also cleared up.

Alice Heffernan January 9, 2014

This is exciting news. I had a mastectomy 10 years ago, followed by 6 months of chemotherapy treatment. Because my cancer was receptor negative I was told that Tamoxifen wouldn’t have helped. Is Anastrozole also not used in cases such as mine?

Joan December 29, 2013

As I have been taking Tamoxifen for almost 5 years following lumpectomy L breast and radiotherapy, but developed osteoarthritis necessitating L and R hip replacement, I wish to know if there is any data available which would implicate the oestrogen suppressing Tamoxifen as a cause of cartilage breakdown.

My experience of the onset of osteoarthritis at 62 is a unique occurrence in my family. I was not overweight when OA developed and took regular exercise (swimming and walking).

Martin Ledwick December 17, 2013

Hi Sheila Reid. Tamoxifen can be a useful treatment for men who develop breast cancer, but there is less research information about how well other hormonal treatments like anastrazole work in men. If a man has a family history of breast cancer, his risk of getting breast cancer (although probably higher than for men without a family history) is still not nearly as high as for women with a family history. So it is less likely that the hormonal preventatives would give these men as strong a benefit. The IBIS trial only looked at preventing breast cancer in women with a family history.

Martin Ledwick, Head Information Nurse, Cancer Research UK

Nikki Smith December 17, 2013

S Ruskin – that’s an interesting point, thank you for your comment. In the IBIS I trial, researchers found slightly higher reduction in the risk of breast cancer for pre-menopausal women compared to post-menopausal women (a 33 per cent reduction in risk for women before menopause and a 23 per cent reduction in risk for those who had been through their menopause).
This suggests that tamoxifen may be particularly useful for women before menopause, when anastrozole can’t be used. It’s important to note that these two drugs have not been tested in a head-to-head trial to compare them thoroughly, but it’s useful to see this figure for context.

Juliet Morley December 16, 2013

Great article, Nikki – interesting, really well written and easy to understand the science

Sheila Reed December 13, 2013

can a man take anastrozole instead of risking the side effects of tamoxifen?

S Ruskin December 12, 2013

Can you (or the researchers) show the tamoxifen cases without pre-menopausal women to show a more useful comparison? Thanks

Jayne Smith December 12, 2013

ANASTROZOLE.Sounds good,and I’m pleased to say have been taking this since late 2009,so am in my last year of 5 years,post mastectomy and lymph node removal and chemotherapy.Have had point discomfort and hot flushes,but could have been far worse.