Hormonal therapies

Hormonal therapies are treatments for women who have hormone receptors on their breast cancer cells.

Hormonal therapies are treatments for women who have hormone receptors on their breast cancer cells.Hormonal therapies lower the level of female hormones in the body or change the way the body responds to female hormones.

For women with early breast cancer, hormonal therapies reduce the risk of breast cancer coming back (in the breasts and in other parts of the body). Some hormonal therapies have also been shown to increase the chance of survival for women with breast cancer.
For women with metastatic breast cancer, hormonal therapies can slow or stop the growth of metastatic breast cancers and can relieve symptoms. For some people, hormonal therapies can make the cancer smaller. The benefits of treatment with hormonal therapies for women with metastatic breast cancer can last for some time – sometimes for years.

Hormonal therapies used to treat breast cancer are not the same as hormone replacement therapy (HRT) used to manage symptoms of menopause.

Find out more about:

[accordion]

Hormone receptors

When breast cancer cells have hormone receptors on them, it means the growth of the cancer cells is affected by female hormones. Breast cancer cells with hormone receptors on them are said to be ‘hormone receptor positive’.

There are two types of hormone receptors – oestrogen receptors (ER) and progesterone receptors (PR). Hormonal therapies stop hormone receptor-positive breast cancer cells from growing.

Types of hormonal therapy

There are different types of hormonal therapy for breast cancer. The type of hormonal therapy recommended for women with hormone receptor-positive breast cancer depends on whether the woman has reached menopause

Anti-oestrogens
Anti-oestrogens work by stopping breast cancer cells from getting oestrogen. The most common anti-oestrogen is tamoxifen. Tamoxifen can be used to treat women of any age, regardless of whether they have reached menopause. Tamoxifen is taken as a single tablet every day, usually for 5 years.

Fulvestrant (Faslodex®) is another anti-oestrogen that is sometimes used in the treatment of metastatic breast cancer. It is given as a monthly injection into the muscle of the buttock. It may be recommended if other hormonal therapies have stopped working or if a woman cannot take tablets because she’s feeling sick.

Aromatase inhibitors
Aromatase inhibitors work by stopping androgens from being changed to oestrogen. Examples of aromatase inhibitors include anastrozole (Arimidex®), letrozole (Femara®) and exemestane (Aromasin®). Aromatase inhibitors are only effective for women who have gone through menopause permanently.

Aromatase inhibitors are not suitable for women who:

haven’t yet reached menopause
are in the middle of menopause
have temporarily stopped having menstrual periods because of chemotherapy.
Aromatase inhibitors are taken as a single tablet every day, usually for 5 years.

Ovarian treatments
Ovarian treatments work by stopping the ovaries from making oestrogen. Drugs like goserelin (Zoladex®) stop the ovaries from making oestrogen temporarily. They only work while the woman is taking the drug. This is called ovarian suppression.

Oestrogen production can be stopped permanently by removing the ovaries surgically (oophorectomy) or giving radiotherapy to the ovaries. Ovarian treatments are only suitable for women who have not yet reached menopause.

Progestins
Progestins are artificial forms of the female hormone progesterone. They are sometimes used for women with metastatic breast cancer. The most common progestins are megestrol acetate (Megace®) and medroxyprogesterone (Provera®). Progestins are given as a tablet.

Side effects

Some side effects are common to all hormonal therapies, and some only happen with certain therapies.

Everyone is different in how they respond to treatment. For some of the newer drugs, such as aromatase inhibitors, we do not yet know all the long-term side effects.

Common side effects

All hormonal therapies can cause menopausal symptoms.

Treatment with hormonal therapies can sometimes cause permanent menopause. Women who have not yet reached menopause and hope to have children in the future should talk to a fertility specialist about options before starting treatment.

Symptoms include:

hot flushes
vaginal dryness
reduced libido (sex drive)

The severity of these symptoms varies between women and between different treatments. These side effects often improve after treatment stops.

There are treatments that can help with these problems.

Less common side effects

Different hormonal therapies have different side effects.

Side effects of tamoxifen

Rare side effects of tamoxifen include an increased risk of:

blood clots
stroke
changes in vision.

Tamoxifen can also cause changes to the lining of the womb (uterus) and in rare cases has been associated with an increased risk of cancer of the uterus.

It’s important to see a doctor immediately if any new or unusual symptoms develop, in particular:

irregular vaginal bleeding
chest pain
warmth, pain, swelling or tenderness in an arm or leg.

Irregular vaginal bleeding doesn’t mean that a woman has cancer of the uterus but it’s important to be examined by a doctor to be sure.

It’s important to balance the risk of these rare side effects against the fact that anti-oestrogens lower the risk of breast cancer coming back and dying from breast cancer. Tamoxifen may have some other benefits in addition to treating breast cancer, including reducing the risk of osteoporosis and lowering cholesterol levels.

Side effects of aromatase inhibitors

Side effects of aromatase inhibitors include:

pain in bones or joints (arthralgia)
an increased risk of osteoporosis, which may increase the risk of bone fractures.

Doctors may measure a woman’s bone density before prescribing an aromatase inhibitor if she is at increased risk of osteoporosis. Calcium and vitamin D tablets may be recommended for women taking an aromatase inhibitor. Treatments are available that can improve bone strength.

A painkiller such as paracetamol can be helpful for women who experience pain in the bones or joints.

Long-term side effects of aromatase inhibitors are still being studied. For example, studies are investigating the effects of aromatase inhibitors on memory, concentration and heart disease.

Side effects of ovarian treatments

Surgery to remove the ovaries or radiotherapy to the ovaries causes permanent menopause. Women who have these treatments can no longer have children naturally.

Drugs that stop the ovaries from working also cause menopause, but this usually only lasts while taking the drugs. However, the effects of these drugs may be permanent if a woman is close to her natural menopause when she starts treatment.

Side effects of progestins

Treatment with progestins may increase a woman’s appetite, which means she might put on weight. Other possible side effects include muscle cramps and slight vaginal bleeding (spotting).

Menopause and oestrogen production

All women produce the female hormone oestrogen; however, it’s made differently by the body before and after menopause.

Before menopause (pre-menopause) oestrogen is made mainly by the ovaries.
Around the time of menopause (peri-menopause), the ovaries stop making female hormones, including oestrogen. This usually happens when women are in their late 40’s and early 50’s. Symptoms of menopause include irregular menstrual cycles, hot flushes and sleep disturbances.
After menopause (post-menopause), monthly menstrual periods stop. The body still makes small amounts of oestrogen by changing hormones called androgens into oestrogen. Androgens are produced by the adrenal glands, which are above the kidneys. A hormone called aromatase changes androgens into oestrogen. Aromatase is produced mainly by fatty tissue.

Deciding about hormonal therapies

When deciding about hormonal therapies it’s important to consider the likely benefits and possible side effects of the different treatments.

Hormonal therapies and early breast cancer

For women with early breast cancer, the long-term benefits and risks of taking tamoxifen are well known. Tamoxifen reduces the risk of breast cancer coming back and improves survival.

Studies have shown that treatment with an aromatase inhibitor reduces the risk of breast cancer coming back more than tamoxifen. However, studies have not been going long enough to say whether aromatase inhibitors improve survival more than tamoxifen. Also, we do not yet know the long-term side effects of aromatase inhibitors.

For post-menopausal women with a higher risk of breast cancer coming back, the short-term benefits of aromatase inhibitors outweigh the risks of side effects (both known and unknown).

For post-menopausal women with a lower risk of breast cancer coming back, it’s possible that long-term side effects of aromatase inhibitors (as yet unknown) outweigh the short-term benefits of treatment compared with tamoxifen.

CYP2D6 test for the effectiveness of tamoxifen

A number of consumers have raised questions about the effectiveness of CYP2D6 genotype testing for women considering tamoxifen as treatment for breast cancer.

There have been a number of studies looking into the potential role of CYP2D6 genotype testing (a blood test) as a marker for whether an individual will be resistant to treatment with tamoxifen.

Currently, there is not enough evidence to recommend routine testing for the CYP2D6 genotype when making clinical decisions regarding the use of tamoxifen in either pre or post menopausal women.

Cancer Australia recommends consideration of the use of adjuvant hormonal therapy for most women with hormone receptor-positive early breast cancer. Women should make decisions about which hormonal therapy is most suitable for them in consultation with their medical oncologist.

As the biology of breast cancer is becoming better understood, the management of breast cancer is increasingly being tailored according to patient and tumour factors. Cancer Australia will continue to monitor new evidence and provide updated information as appropriate.

Hormonal therapies and metastatic breast cancer

For women who haven’t yet reached menopause and who have hormone receptor-positive breast cancer, treatment usually starts with tamoxifen with or without an ovarian suppression drug.

For women who have reached menopause and who have hormone receptor-positive breast cancer, treatment usually starts with an aromatase inhibitor. If a woman is already taking tamoxifen when her metastatic breast cancer is diagnosed, it’s recommended that she changes to an aromatase inhibitor.

If a woman’s metastatic breast cancer stops responding to treatment with an aromatase inhibitor, or if she has side effects that are difficult to manage, she may be advised to change to a different type of hormonal therapy.

In general, fulvestrant and progestins are only recommended if other hormonal therapies have stopped controlling the cancer.