Tamoxifen

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Your doctor has recommended a medication called tamoxifen, which is now used widely to treat breast cancerTamoxifen is taken by mouth in tablet form. It comes in different strengths; 10mg, 20mg and 40mg. The drug is also manufactured under different brand names and these may appear on the tablets. This page provides extra information about your medicine, summarises possible side effects and methods to alleviate them. 

How do they work? Some tumours such as breast cancer are stimulated by the body's own female hormone (Oestrogen). Stopping the body's oestrogen reaching the tumour can cause the cancer cells to stop growing and in some cases shrivel up and die completely (self destruct - apoptosis).  Tamoxifen stops oestrogen stimulating a cancer cell in two main ways. It stops the cancer cells ability to read the oestrogen in the blood stream. Breast cancer cells have receptors in the same way as a TV needs an aerial. If the aerial is damaged the TV can't show a clear picture. In the same way if the receptor on the cell is blocked it can't be influences by the body's hormones, despite often normal levels in the blood stream. In this case the receptors are called oestrogen receptors and are blocked by  tamoxifen. This is why tamoxifen is sometimes referred to as a receptor antagonists. These receptors can be measured by performing a special test on the tissue removed from the tumour (Oestrogen receptor tests). If a tumour is oestrogen receptor positive it is much more likely to respond to tamoxifen.  

How are they taken? Tamoxifen is usually prescribed as a single daily dose. Many women like to take it at the same time each day – the actual time does not matter. Some women prefer to take it with food as it may cause nausea and leave a metallic taste in your mouth. Some women prefer to take it last thing at night because it reduces the hot flushes in the day . Try to find a convenient time and stick to it as its easier to remember to take the tablets in the long term.

If you forget to take your tablet don’t panic – 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 couple of weeks before you run out of the tablets and make sure you have plenty for holidays etc.

What are they taken for? There are three main reasons why hormone therapy is recommended for patients with breast cancer:-

 Adjuvant therapy - In this situation tamoxifen is given to patient after their breast cancer has been removed with surgery as an added insurance policy to reduce the chance of it returning in another part of the body in the future. Trials are underway to decide exactly how long tamoxifen should be taken after breast cancer has been diagnosed. It is commonly prescribed for five years although some doctors prescribe it for two years and others indefinitely. It is usually recommended in all ladies who's tumour is seen to have oestrogen receptors.  Trials have shown that in this case there is an improved chance of cure by an extra 49%. Women benefit before and after the menopause by an equal amount. Many women take tamoxifen for 5 years but an alternative is to take it for 1-3 years then switch to an aromatase inhibitor for the remaining adjuvant cause.

Neoadjuvant therapy - For breast cancer this is usually reserved for situations where the surgeon does not feel the tumour could be safely removed at operation with lumpectomy (removal of lump) and has recommended mastectomy (removal of breast). Tamoxifen is occasionally given first in an attempt to shrink the tumour to make it possible to remove the lump and not the breast. 

Palliative/ primary therapy - In this situation the aim is not  to cure, but to control or shrink the tumour especially if it is causing a specific symptom.  For example,  it is used to controlled disease which has spread from the breast to another part of the body (metastasised) such as bone, liver or lung. Alternatively,   tamoxifen is used as the primary treatment for a breast lumps in patients, usually elderly who are unfit or unwilling to have surgery.

In these latter two categories, your oncologist would require a full re-assessment of your disease at regular intervals to check whether it is working effectively. If not, the regime could be stopped or changed.

There is another category which is at the research stage but may be talked about in the press. Tamoxifen is given to offer protection from breast cancer to women who have a high risk of developing the disease. High risk is defined as having one or more close relatives (mother, sister) who had breast cancer before they were 50. The trials will run for several years ands it is hoped that tamoxifen will be successful in preventing the development of breast cancer in these women.

What are the possible side effects of tamoxifen? Because people react to drugs in different ways, it is impossible to predict who is going to have side effects. Many women who take tamoxifen have no side effects at all while others will experience them. Some women find that one brand of tamoxifen causes more or less side effects than another, so if you experiencing side effects you may wish to ask your doctor if you can change to a different brand.

If side effects are severe, you may have to stop tasking the drug and a different hormonal drug may be prescribed. The commonest side effects, apart from nausea, are hot flushes and sweats, particularly at night.

Flushes and sweats;  Sometimes the flushes will gradually lessen over the first few months but some women continue to have them for as long as they take tamoxifen. There are a number of self help strategies to help reduce or control hot flushes and sweats. For example, Some women find it helpful to avoid or cut down on tea, coffee, nicotine and alcohol. Evening primrose oil has been reported to be helpful in reducing sweats but it does not work for all women and it is very expensive. There are a lot of calories in Evening Primrose Oil so it may be fattening in some women. Some women have found complementary therapies have helped, and your GP may be able to give you details about obtaining these on the NHS.  If you find your own therapist makes sure he or she is properly qualified and registered. If these measures do not work medical intervention may be appropriate: Nausea and indigestion;  Feelings of sickness (nausea) and indigestion are fairly common but can often be relieved by taking your tablet(s) with foods or milk or at night. Although mild nausea is quite common initially it usually wears off after a few weeks.

Weight gain; Weight gain can be a side effect of tamoxifen and this is sometimes due to water retention but at other times a consequence of a eating more either due to a increased appetite or mild nausea - "to settle the stomach" . See coping with weight gain.

Change in periods; Women who have not yet reached the menopause may notice their monthly periods change – they may become irregular, lighter or sometimes stop altogether. Some women also notice an increase in vaginal discharge and vulval itching.

Less common side effects include depression, tiredness and dizziness. Very rare side effect of tamoxifen includes:

Rarely, women who are prescribed tamoxifen for advanced cancer, where there has been spread to the bones, may experience something called ‘tumour flare’ when they start taking Tamoxifen. This can cause a raised level of calcium in the blood (hypercalcaemia) with symptoms of nausea, vomiting and thirst. Often a short stay in hospital is necessary until the calcium levels have been reduced.

Tamoxifen can increase the effect of the drug warfarin, used to thin the blood in people prone to blood clots. If you are taking warfarin let your doctor know straight away.

 

What are the long term side effects of tamoxifen?

As tamoxifen is a relatively new drug the full long term effects of the drug are still being assessed through patient studies. In recent years there has been publicity about the long term effects of tamoxifen and its possible link with other types of cancer.

Tamoxifen studies have shown that women who take high doses of tamoxifen over a long period of time may have a slightly increased risk of developing cancer of the womb (endometrial cancer). This is very rare if the drug is taken for less than 5 years. However, this risk has to be weighted against the benefits of tamoxifen. If detected early, treatment for endometrial cancer is usually very successful.

Early warning signs are abnormal vaginal bleeding – although this is often caused by a non-cancerous condition such as a polyp. If taken for longer than 5 years, in some cancer centres women are given regular gynaecological check-ups to detect signs of endometrial cancer. An ultrasound scan, using sound waves, may be done to check for signs of endometrial cancer. An ultrasound scan, using sound waves, may be done to check for signs of change in the womb lining. A small probe is inserted into the vagina and the doctor can look at the scan on a screen. Any changes can be seen straight away. The scan is safe and only takes a few minutes.

Some studies on rats have shown a link between tamoxifen and liver cancer but this has not been proven in humans. There is little doubt that for most women the beneficial effects of tamoxifen far outweigh the risks.

 

Other benefits of tamoxifen There is some evidence suggesting that while you are taking tamoxifen it can lower the level of fat or lipids in your blood – and high levels of fat contribute to heart disease.

It is also thought that tamoxifen may help to prevent bone loss which can reduce the risk of osteoporosis (thinning of the bone) in some women.

 

Alternatives to tamoxifen  In post menopausal women it may be possible to take an Aromatase inhibitor drug . In the metastatic setting they may even be more effective than tamoxifene equal in effect to tamoxifen and trials are underway in the adjuvant setting. Other forms oestrogen receptors agonist are available which are currently under investigation e.g. toremifene

 


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