Hormones are substances that occur naturally in the body, where they control the growth and activity of normal cells. Female hormones, particularly oestrogen, can encourage the growth of some breast cancer cells. So, drugs which lower the level of oestrogen in the body, or that block oestrogen from attaching to the cancer cells are used as treatment for some types of secondary breast cancer.

Many women are prescribed tamoxifen (one type of hormonal therapy) after their initial cancer treatment. In this situation, if the cancer comes back, a different type of hormonal therapy (such as an aromatase inhibitor) may be used. Aromatase inhibitors (see below) are becoming more widely used after primary breast cancer treatment, and in this situation tamoxifen or a different type of aromatase inhibitor may be used if the cancer comes back. Some women have several types of hormonal therapy – one after the other.

They stimulate the growth of hormone sensitive tissues, such as the breast,. and can also stimulate the growth and spread of breast cancer. Two methods help combat hormone dependent breast cancer. The first is by taking certain drugs that can block hormone production or change the way hormones work to fight the cancer throughout the body. The second is remove the ovaries, which secrete hormones.

The breast cancers that are hormonedependent are referred to as estrogen receptor positive (ER+) and progesterone receptor positive (PR+). Receptors are areas on the surfaces of cells where hormones can bind to promote the growth of breast cancer. Doctors can prescribe hormone therapy to block those hormone receptors in order to “starve” the cancer cells. Hormones do not promote the growth of tumors that are estrogen receptor negative (ER-) or progesterone receptor negative (PR-). Patients who have ER- and PR- breast cancers are not candidates for hormone therapy.

Hormone therapy drugs include tamoxifen (Nolvadex) and three others that are collectively referred to as aromatase inhibitors (AIs). All are taken orally each day. Tamoxifen blocks estrogen after it is produced and can reduce the risk of developing breast cancer in the same (ipsilateral) or opposite (contralateral) breast. Tamoxifen may be taken by women who are either premenopausal or postmenopausal as well as by men. Common side effects of tamoxifen include hot flashes, indigestion or feeling sick, sweats, vaginal dryness, vaginal discharge and weight gain. Rare, but more serious, side effects include blood clots (thrombosis), endometrial problems, eye problems and stroke.

AIs include anastrazole (Arimidex), letrozole (Femara) and exemestane (Aromasin). These drugs block the production of estrogen and are not prescribed for premenopausal women Side effects include hot flashes, joint pain, muscle aches, headache, depression and increased risk of bone fracture.
Side effects vary from person to person. Be sure to discuss with your healthcare provider the specific side effects of the drug you will be taking.

Premenopausal women
In women who have not had their menopause (change of life), most of the oestrogen in the body is produced by the ovaries. A small amount of oestrogen is made by changing androgens (produced by the adrenal glands) into oestrogen.

Postmenopausal women
After the menopause, oestrogen is produced mainly from male hormones (androgens) made by the adrenal glands. The androgens are changed into oestrogens in the fatty tissues of the body. Changing androgens into oestrogens is controlled by an enzyme called aromatase.

When hormonal therapies are used
Hormonal therapy only works for women who have oestrogen-receptor positive cancers, and can be effective in controlling slow-growing cancers affecting the bones, the lymph glands, the fatty tissue under the skin or the skin itself. It can also be used for secondary breast cancer in the liver and lung.

One advantage of hormonal treatments is that they are easy to take and although side-effects can occasionally be troublesome, they are rarely serious. Another advantage is that there are many different hormonal treatments available, and if one does not work, or stops working, others can be tried. Hormonal therapies usually need to be taken for a few weeks before you can tell if they are working.

Many hormonal treatments are available and more are being developed all the time. The commonly used ones are discussed below.

Anti-oestrogens
Tamoxifen
Tamoxifen is a type of anti-oestrogen drug. It works by stopping oestrogen in the body from attaching to breast cancer cells and encouraging them to grow. In the UK, it is currently the most commonly used hormonal therapy for breast cancer. It can be very effective in controlling secondary breast cancer for many women and can be taken by women who are premenopausal or postmenopausal. Tamoxifen treatment can be continued for as long as it is effective in preventing the cancer cells from growing.

Tamoxifen is taken as a daily tablet. The side effects may include hot flushes and sweats, a tendency to put on weight, dryness of the vagina or an increased discharge from the vagina. These side effects are usually mild and may reduce over time. Some women continue to find some of the side effects of tamoxifen troublesome. If this happens, it is helpful to discuss this with your doctor as there are ways of reducing these effects. Other hormonal therapies can also be used instead of tamoxifen. Cancerbackup has a section on breast cancer and menopausal symptoms, which has helpful tips.

In post-menopausal women tamoxifen can slightly increase the risk of womb cancer, blood clots in the leg or lung and strokes. Although this sounds very frightening, these effects are very rare and almost always curable and treatable. The benefits of tamoxifen in treating the breast cancer outweigh the risks of side effects for most women.

Women who have secondary breast cancer in a bone may find that tamoxifen makes the bone pain worse for the first few days. This soon eases, but it is important to know that it might happen and that it is a temporary side effect of the drug. It is important to tell your doctor if it happens.

Fulvestrant (Faslodex®)
Fulvestrant is a new anti-oestrogen drug that is given as an injection. It is given once a month. It may be used after treatment with tamoxifen or aromatase inhibitors (see below). It may also be used if women cannot take tablets or may forget to take tablets. The side effects are similar to tamoxifen.

Drugs that block oestrogen production
Aromatase inhibitors
A group of drugs called aromatase inhibitors work by blocking the production of oestrogen in fatty tissues and the adrenal glands. They are only used in women who have had their menopause. Currently, research trials are testing whether they can be effective when used with goserelin (Zoladex®) in women who have not had their menopause.
Anastrozole (Arimidex®) is an aromatase inhibitor which is taken once a day as a tablet. It tends to cause few side effects, and those that do occur tend to be mild. It can cause vaginal dryness, nausea (feeling sick), and muscle and joint pain. It is less likely to cause hot flushes than tamoxifen.
Letrozole (Femara®) is also taken once a day as a tablet. Side effects are usually mild, and are similar to those of anastrozole.
Exemestane (Aromasin®) is also taken as a tablet once a day. The side effects tend to be mild and are similar to anastrozole, but it may also cause diarrhoea in some women.

Progestogens
If the secondary breast cancer cells are not controlled by tamoxifen or aromatase inhibitors, artificial progesterone (progestogen) treatment may be used instead.

Progesterone is another hormone that occurs naturally in women. Progestogens are stronger than progesterone and can be given as tablets or by injection into the muscle of the buttock. The commonest ones are megestrol acetate (Megace®) and medroxyprogesterone acetate (Farlutal®, Provera®). Injections may be given by your doctor or nurse.
Progestogens tend to cause more side effects than aromatase inhibitors. Although some women may feel slightly sick, most women find that progestogens increase their appetite. This may make them put on some weight, particularly in the stomach area. Some women also notice mild muscle cramps or slight vaginal bleeding (spotting). Rarely, progestogens can cause breathlessness, and if this happens you should let your doctor know.

Pituitary downregulators

Drugs known as pituitary downregulators reduce the production of oestrogen-stimulating hormones from the pituitary gland. This lowers the level of oestrogen in the body. Pituitary downregulators can be used to lower oestrogen levels in women who have not yet had their menopause. They have the same effect as removing the ovaries or giving them radiotherapy, but the effect is reversible. As a result, many doctors now recommend these drugs, rather than removing the ovaries with surgery or giving radiotherapy to stop them working.
Because these drugs lower the amount of oestrogen circulating in the blood, they can be an effective treatment for women with breast cancer who have not had their menopause. They only work for oestrogen-positive breast cancers. The most commonly used pituitary downregulator in breast cancer is goserelin (Zoladex®). Goserelin brings on a temporary menopause, so many of its side effects are similar to those of the menopause and include hot flushes and sweating, lowered sex drive, headaches and mood changes.
Many younger women find the symptoms of this early menopause difficult to deal with. Although some menopausal symptoms can be uncomfortable, many can be effectively treated.

Surgery or radiotherapy to the ovaries
In women who have not yet had the menopause, it is sometimes possible to stop the growth of their secondary breast cancer by stopping the ovaries from producing oestrogen. This can be done either by removing the ovaries during an operation or by giving three or four radiotherapy treatments to the ovaries. In both cases, the ovaries stop producing female hormones, which brings on the menopause.

When surgery is used, periods stop immediately. It needs a hospital stay of 1–2 days.
When radiotherapy is given to the ovaries, women usually have one more period, which may be heavy. Periods then stop completely. Contraception should be continued for three months after radiotherapy.

These treatments mean that a woman will no longer be able to have children. This definite end to being able to have children can be very distressing to women already coping with secondary breast cancer – whether or not they have completed their families.

Health care staff will understand the emotional effect this treatment can have on women. You may find you want time to discuss the treatment with your partner, or someone close to you, before deciding to go ahead. You can also contact Cancerbackup’s Cancer Support Service to talk through your feelings.