This information is about aromatase inhibitors as a treatment for women with early breast cancer. It should ideally be read with our general information about breast cancer.

Aromatase inhibitors (AIs) are a type of hormonal therapy that work in a different way to tamoxifen. To understand how AIs work, it helps to know a little about the way oestrogen is made.

In women who have not had their menopause (pre-menopausal women), the main source of oestrogen is the ovaries. In women who have had their menopause (post-menopausal women) oestrogen is made by a process known as aromatisation. This is an activity in which sex hormones (androgens) produced by the adrenal glands are turned into oestrogen in the fatty tissue of the body. A chemical in the body called aromatase makes this happen.

Aromatase inhibitors block the process of aromatisation, and so reduce the amount of oestrogen in the body. This means that the hormone receptors are exposed to less oestrogen and the cancer cells receive fewer signals to divide. AIs are currently only suitable for post-menopausal women, although research is being carried out into using them in pre-menopausal women who have been put into a temporary menopause by using medicines such as Zoladex®.  Your doctor can give you more information on this or you can talk to our nurses.

There are three AIs currently in use:

• anastrozole (Arimidex®)
• exemestane (Aromasin®)
• letrozole (Femara®).

Aromatase inhibitors have been used to treat women with advanced (secondary or metastatic) breast cancer since the mid-1990s and their use in this situation is well established. This information is about AIs for early breast cancer, but if you would like information about their use in advanced breast cancer you can contact our nurses.

Several studies have looked at the effectiveness of AIs in primary (early) breast cancer when compared to tamoxifen. The results have been encouraging and the three main aromatase inhibitors are now licensed to treat post-menopausal women with ER-positive early breast cancer.

A study called the ATAC trial compared five years of tamoxifen with five years of Arimidex in post-menopausal women with early breast cancer. Women taking part in this trial had all been treated with surgery and radiotherapy. The results showed that breast cancer was slightly less likely to come back in women taking Arimidex than in those taking tamoxifen. The results also showed that the women taking Arimidex tended to have fewer side effects than those taking tamoxifen.

Several studies have looked at what happens when women switch to Arimidex after taking tamoxifen for 2–3 years. Recent research of the three main studies found that women who switch to Arimidex have a lower chance of their breast cancer coming back; and improved chances of survival. The authors of the study suggest that doctors should consider switching postmenopausal women to anastrozole after 2–3 years of tamoxifen.

Arimidex and the other AIs do not usually cause many side effects, but the main long-term problem that can occur is thinning of the bones (osteoporosis). For this reason, it is recommended that some women have regular scans to check their bone density – your doctor will tell you if this is needed in your case. It is important that women taking AIs ensure their diet includes enough calcium and vitamin D.

The National Institute for Health and Clinical Excellence (NICE) advises doctors on the use of treatment in the NHS in England and Wales. It has approved the use of Arimidex for women with early oestrogen-receptor positive breast cancer.

The International Exemestane Study (IES) looked at women who had been treated for early breast cancer and had been taking tamoxifen for two years, and whether switching to Aromasin after 2–3 years of tamoxifen was more effective than staying on tamoxifen for five years.

The results from this trial showed that changing to Aromasin after two to three years of tamoxifen not only reduced the risk of breast cancer coming back, but also improved the survival rate of women whose cancers were hormone-receptor positive. Aromasin has been approved by NICE as a treatment for women with early, oestrogen-receptor positive breast cancer.

Although these findings are very interesting, they do not mean that all women who are currently taking tamoxifen should change to Aromasin after two or three years. Longer follow-up is needed and, as with Arimidex, Aromasin has side effects.

In 2003, the provisional results of a clinical trial were published. Post-menopausal women who had completed a five-year course of tamoxifen treatment for early breast cancer were then given either Femara (for up to another five years) or an inactive tablet (a placebo). The results showed that breast cancer came back less in women who took Femara. There were also fewer new cases of breast cancer.

The trial was stopped because of the significant benefits discovered. All women who were taking an inactive tablet were offered Femara (but not all took the offer up). In 2006, further analysis of the research was published. This showed that the women who switched from the placebo to Femara had a slightly lower chance of their cancer coming back compared with the women who did not.

An international research group (called the Breast International Group (BIG)) is running a comprehensive study (the BIG 198 study) into the effects of Femara. It randomly allocates women to receive one of the following four treatments:

• five years of tamoxifen alone
• five years of Femara alone
• two years of tamoxifen followed by three years of Femara
• two years of Femara followed by three years of tamoxifen.

The only results available so far are the direct comparison of five years of tamoxifen and five years of Femara. Women who took Femara had less chance of their breast cancer returning.

The Scottish Medicines Consortium (SMC) advises doctors on the use of treatments in the NHS in Scotland. It has approved Femara as a treatment for post-menopausal women with early breast cancer. The drug can now be given as a first hormonal therapy after diagnosis or following five years of tamoxifen treatment. The guidance that the SMC gives to doctors suggests that it may be of greater benefit to women whose breast cancer had spread to their lymph nodes by the time it was first diagnosed.

In November 2006, NICE approved the use of Femara for women with early oestrogen-receptor positive breast cancer in England and Wales.

Femara can also be used in early breast cancer to try to shrink the tumour before surgery.

The trials mentioned here have looked at AIs in comparison with tamoxifen. There are also some ongoing trials directly comparing the effectiveness of different types of AIs but no results from these are available at the time of writing.

Arimidex, Aromasin and Femara are all taken as tablets once a day. They should ideally be taken at around the same time every day.

Each person's reaction to any medicine is different. Most people have very few side effects with AIs.

The most common side effects and menopausal symptoms are outlined below. We have not included those that are very rare and therefore extremely unlikely to affect you. If you notice any effects that are not listed here, please discuss them with your doctor or nurse.

Some people may have the following side effects to varying degrees:

Risk of osteoporosis Women who have osteoporosis (weakened bones) or are at risk of it, should have their bone strength assessed before and during treatment with AIs. Some women may need treatment to help prevent osteoporosis from developing.

Joint pains/stiffness Some women have pain and stiffness in their joints while taking AIs. Let your doctor know if these effects are troublesome. It may be helpful to take mild painkillers.

Hot flushes and sweats These are usually mild and may stop after a period of time. Sometimes women find that avoiding or cutting down on tea, coffee, nicotine and alcohol can reduce sweats. Recent research suggests that progestogen or some antidepressants may be helpful in controlling this side effect. Your doctor or nurse can discuss this with you.

Some women find that complementary therapies help, and your GP may be able to give you details about getting these on the NHS.

If you are having troublesome hot flushes, discuss these with your doctor.

Vaginal dryness may occur while using AIs. Gels that can help to overcome the dryness are available. These can be bought from any chemist or can be prescribed by your doctor.

Nausea (feeling sick), vomiting and diarrhoea These side effects are uncommon. If they occur they can usually be effectively treated, so let your doctor know. Feeling sick can often be relieved by taking your tablet with food or at night. If you have diarrhoea it is important to drink plenty of fluids.

Hair thinning Some women notice that their hair becomes thinner while taking AIs. This is usually mild and the hair goes back to normal after the treatment has finished.

Headaches Some people have headaches whilst taking AIs, but this is rare. It is important to drink plenty of fluids. Let your doctor know if you are getting headaches, as medicines can be prescribed.

Vaginal bleeding Vaginal bleeding (usually in the first few weeks of treatment) has been reported. This is rare and has usually occurred after changing from other hormonal therapies to treatment with AIs. If the bleeding continues, tell your doctor or breast-care nurse.

Tiredness and lethargy Some people feel more tired than usual, especially at the start of treatment. It is important to get plenty of rest. If you are very sleepy, you should take extra care when driving or operating machinery.

Your doctor will discuss with you the different types of hormonal therapy. Together you can decide which one is right for you. At present, tamoxifen is the standard hormonal treatment for early stage breast cancer in both pre- and post-menopausal women. However, there have been very encouraging results from the early aromatase inhibitor studies, and AIs are starting to be used more often for women in the UK with oestrogen-receptor positive early breast cancer.

All three AIs have been licensed for use in early breast cancer, and have recently been assessed by the National Institute for Health and Clinical Excellence (NICE). NICE approves all three drugs for use as extra (adjuvant) treatment following surgery for post-menopausal women with early, oestrogen-receptor positive breast cancer.

Research into AIs for early breast cancer continues as there are still some key questions that need to be answered.  For example:

• How do the different AIs compare to each other? (The trials so far have compared them with tamoxifen but not with each other).
• When is the best time to start taking an AI? – this could be straight away as part of a patient’s initial treatment (first line), or after 2–3 years of tamoxifen (sequentially).
• How long should women take AIs for?
• What are the possible long-term side effects of AIs?
• Are AIs as effective at stopping breast cancer from coming back as tamoxifen?

Your doctor will recommend a particular hormonal therapy based on your current situation. You will have regular follow-up appointments where you can discuss how you’re getting on with the treatment. If you are having troublesome side effects, or your medical situation changes, your doctor may recommend a different treatment.

You can find more detailed information about aromatase inhibitors in our health professionals section.

• AIs may interact with other medicines. Let your doctor know about any medicines you are taking, including non-prescribed drugs such as complementary therapies and herbal drugs.
• Keep the tablets in a safe place where children can’t reach them.
• If your doctor decides to stop the treatment, return any remaining tablets to the pharmacist. Do not flush them down the toilet or throw them away.
• If you are sick just after taking the tablet tell your doctor, as you may need to take another.
• If you forget to take your tablet, do not take a double dose. Let your doctor or nurse know. Don’t worry, the levels of the drug in your blood will not change very much, but try not to miss more than one or two tablets in a row.
• Remember to get a new prescription a few weeks before you run out of tablets, and make sure that you have plenty for holidays, etc.

This section has been compiled using information from a number of reliable sources including:

• ATAC Trialists group. Results of the ATAC trial after completion of 5 years adjuvant treatment for breast cancer. Lancet. 2005. vol 365; 60–62.
• The Breast International Group (BIG) 1–98 Collaborative Group. A comparison of Letrozole and tamoxifen in post-menopausal women with early breast cancer. New England Journal of Medicine. 2005. vol 353 (26); 2747–2757.
• Effectiveness of switching from adjuvant tamoxifen to anastrozole in postmenopausal women. Jonat W et al. Lancet Oncology Published online 17 November 2006.
• Coombes, RC et al. A randomised trial of Exemestane. New England Journal of Medicine. 2004. vol 350 (11);1081–1092.
• Jakesz, R et al. Switching of post-menopausal women with endocrine-responsive early breast cancer to anastrozole. Lancet. 2005. vol 366; 455–462.
• Final Technology Appraisal Hormonal Therapies for the adjuvant treatment of early oestrogen-receptor positive breast cancer. National Institute for Health and Clinical Excellence (NICE); November 2006.
• Winer, Eric P et al. American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for post-menopausal women with hormone-receptor positive breast cancer. Journal of Clinical Oncology. 2005. vol 23 (3); 619–629.