Hormonal therapy

If your cancer is oestrogen receptor positive and/or progesterone receptor positive, you’ll likely be offered hormone therapy (also known as endocrine therapy). It reduces your risk of breast cancer recurrence, and your risk of developing a second breast cancer.

Oestrogen and progesterone are hormones which are naturally produced in the human body. Before menopause, oestrogen is mostly produced by the ovaries. After menopause, when the ovaries are no longer active, a small amount continues to be produced in other tissues such as fat, muscle and adrenal glands.

Normal breast cells contain receptors (proteins) that are able to recognise these hormones and allow them to access the cells, where they release signals encouraging growth and development. All breast cancers are tested for the presence of these oestrogen and progesterone receptors, using tissue taken at the time of biopsy or surgery. Approximately 70% of breast cancers retain these receptors, and rely on these hormones (particularly oestrogen) to grow. These hormone-sensitive cancers are described as oestrogen receptor positive (ER+) and/or progesterone receptor positive (PR+).

By blocking the production of oestrogen, or preventing it from stimulating breast cancer cells, hormone therapy minimises the cancer cells’ exposure to oestrogen. This therapy is only effective in hormone receptor-positive breast cancer and does not work in receptor-negative disease.

Hormone therapy is also used to shrink or slow the growth of a breast cancer when surgery is not appropriate, for example in an older person with other major health issues. It is also used to help shrink advanced stage (secondary or metastatic) breast cancers or slow their growth.

Hormone therapy for breast cancer is not the same as HRT (hormone replacement therapy). HRT raises the level of oestrogen +/- progesterone in the body and is not used in the treatment of breast cancer.

There are three types of hormone therapy commonly used to treat early breast cancer:

1. Tamoxifen
2. Aromatase inhibitors – anastrozole (Arimidex), letrozole (Femara, Letala), exemestane (Aromasin)
   
3. Ovarian suppression with drug therapy or surgery

The choice of hormone therapy is determined by:

• your menopausal status
• your degree of recurrence risk
• your general health
• your individual risk of certain side effects, e.g. deep vein thrombosis/pulmonary embolus (tamoxifen) or osteoporosis (aromatase inhibitors).

Tamoxifen belongs to a group of drugs known as SERMS (Selective oEstrogen Receptor Modulators) that block the effect of oestrogen on breast cancer cells, but allow some oestrogen to nourish other sites (for example, bones and uterus). It’s an “anti-oestrogen” agent that binds to the receptors and prevents oestrogen from entering the cancer cells. This reduces the risk of the cancer coming back in the future and helps prevent breast cancer-related deaths. It also reduces the chance of developing a second breast cancer.

Tamoxifen is the standard hormone therapy for pre-menopausal women with hormone receptor-positive breast cancer but it is also given to post-menopausal women and to men. It’s taken once daily in tablet form.

You may be prescribed tamoxifen for five to 10 years depending on your risk of cancer recurrence, and the benefits of tamoxifen continue long after you stop taking it. Discuss the risks versus benefits in your case with your breast cancer specialist.

Post-menopausal women may sometimes be recommended to switch to an aromatase inhibitor after taking tamoxifen for two to three years. Tamoxifen may also be given in conjunction with Zoladex, another medication that switches off ovarian function in pre-menopausal women.

Tamoxifen has also been shown to reduce the risk of developing breast cancer in women who are at high risk of the disease.

If tamoxifen has been prescribed for you, download the patient information sheet: BCFNZ Tamoxifen information sheet

After menopause, the ovaries stop making oestrogen, but small amounts continue to be produced from the adrenal glands and in fat and other peripheral tissue. An enzyme known as aromatase enables this process by changing other hormones to oestrogen. By blocking the aromatase enzyme and stopping this oestrogen production, aromatase inhibitors reduce the risk of the cancer coming back in the future and help prevent breast cancer-related deaths. They also lower the risk of a second breast cancer developing.

Aromatase inhibitors reduce the amount of oestrogen being produced in the body. They are given to post-menopausal women whose ovaries no longer produce oestrogen. However, some pre-menopausal women who are at high risk of recurrence may be prescribed an aromatase inhibitor along with an injection (Zoladex), which stops the ovaries producing oestrogen. In early breast cancer treatment aromatase inhibitors are usually given only to women as there is limited data about their efficacy in men.

Patients should talk with their oncologist about the benefits of taking aromatase inhibitors for a longer duration than five years. This is balanced with a higher risk of bone-related side effects. The benefit would be greatest for those at the highest risk of recurrence.

If an aromatase inhibitor has been prescribed for you, download the patient information sheet: BCFNZ Aromatase Inhibitors information sheet

Shutting down the ovaries so that they no longer produce oestrogen can reduce the risk of recurrence in pre-menopausal women with higher risk oestrogen receptor-positive cancer.

This can be achieved with drug therapy, surgery or less commonly with irradiation.

Drug therapies

Luteinising hormone blockers GnRH/LHRH agonists

These agents signal the pituitary gland to stop producing luteinising hormone, which is responsible for stimulating the production of oestrogen from the ovaries in pre-menopausal women.

Zoladex (goserelin)

Zoladex is delivered as a small implant which is given by injection under the skin (usually on the abdomen) every 28 days or alternatively at three-monthly intervals. By shutting down the production of oestrogen, the treatment aims to prevent the growth of receptor-positive breast cancer. It is used to lower the risk of recurrence after surgery and is usually given for two years in this situation. Zoladex can be used alone or in combination with tamoxifen or aromatase inhibitors. When used to shrink and control metastatic (secondary) breast cancer the treatment is continued for as long as it is being effective.

Lucrin (leuprorelin) works in the same way as goserelin.

In young women, the ovarian function should recover after treatment ceases (unless you are close to the age of a natural menopause in which case the treatment might induce early menopause).

Oopherectomy (surgical removal of the ovaries)

Permanent and immediate suppression of ovarian function is achieved by surgically removing the ovaries (and usually the fallopian tubes). This can often be done via small “keyhole” incisions in the abdomen, using a laparoscope (a flexible tube with an attached camera). If the laparoscopic method is not appropriate then the ovaries are removed through a short incision in the lower abdomen.

Removing the ovaries results in an immediate and permanent menopause as the production of oestrogen and progesterone from the ovaries is abruptly halted. The symptoms of a surgically induced menopause are usually more intense than those of a more gradual, natural menopause.

Some side effects are common to all methods of hormone therapy and are due to the reduced levels of oestrogen.

These include:

• Hot flushes and sweats
• Nausea
• Vaginal dryness, itching
• Lowered interest in sex
• Fatigue
• Mood changes.

Tamoxifen and aromatase inhibitors also produce some different side effects. You may experience some of the side effects listed, but are unlikely to experience them all.

For most people who are recommended to take hormone therapy for breast cancer, the risks of treatment are outweighed by the benefits.

Here is a list of possible side effects that might be experienced on tamoxifen and aromatase inhibitors:

Many of the common side effects of hormonal therapies can be reduced or managed with the help and advice of your specialist breast cancer team.

Hot flushes

• Regular exercise has been shown to reduce the frequency and intensity of hot flushes.
• Take note of anything that might trigger your hot flushes, e.g. hot drinks, alcohol, spicy food, hot temperatures.
• Wear loose, natural fabrics (especially cotton) and dress in layers so you can remove some layers when you are feeling hot..
• It may be helpful to carry a small portable fan with you.
• Try to maintain a healthy body weight.
• At night, take a cool shower before bed. Sleep with a fan nearby.
• A pet cooling mat placed under the sheet or pillow may help. These are available online and from pet shops and major hardware stores.
• If your hot flushes/night sweats are intolerable, talk to your oncologist to see if you might be able to change medications or try some medication to reduce the flushes.

It is not advised to take herbal products such as Black Cohosh. These often contain phytoestrogens (plant oestrogens) and the safety of taking these supplements with hormone therapy for breast cancer has not been established. Talk to your oncologist before taking any herbal remedies.

Vaginal dryness or irritation

Lowered oestrogen levels cause the tissues of the vagina to become thin, dry and less elastic. The vagina becomes slightly shorter and narrower. (These changes also happen with menopause.)

Water-based lubricants such as Sylk can reduce the discomfort, particularly during sex. Vaginal moisturizers such as Replens (available online and from some pharmacies) help to hydrate the vaginal tissue and have a long-lasting effect (up to three days at a time).

Vaginal discharge

A small amount of clear or white vaginal discharge is normal for many women but hormone therapy for breast cancer may cause an increase in the discharge volume. Wear loose, cotton underwear and panty liners if needed. Report any odour, discolouration or blood staining to your doctor.

Nausea

This is quite common when starting hormonal therapy and often passes as your body learns to tolerate the drug. It may help to take the medication with food or at night before going to bed.

Bone and joint pain

It’s important to stay physically active to keep the muscles around your joints flexible. Regular exercise has been shown to reduce joint pain caused by hormone therapy.

Common mild analgesics such as paracetamol or some anti-inflammatories can also help, so talk to your doctor to see if these medications are appropriate for you. Hot packs may be soothing, yoga may be helpful and some people have gained relief with acupuncture.

Loss of bone density

If you have a strong family history of osteoporosis or a personal history of a fracture after a minor fall, talk to your doctor about having a DEXA scan to measure your bone density. Ensure you have a healthy diet incorporating adequate calcium.

Vitamin D also aids bone health and may be prescribed to you if you are taking an aromatase inhibitor.

Weight-bearing exercise and resistance training also help maintain bone density.

You can estimate your risk factors for osteoporosis here: Bone health risk factor test

Deep vein thrombosis, pulmonary embolus and endometrial cancer are rare side effects of Tamoxifen. It’s important to urgently report any calf pain and swelling, shortness of breath or abnormal vaginal bleeding to your doctor.

If you are experiencing any unpleasant side effects don’t suffer in silence. Talk with your breast care/oncology nurse or doctor about any side effects you may be having. There may be ways to reduce the intensity of your symptoms or there may be alternative medications that suit you better.

Hormone therapy improves breast cancer outcomes, so your specialist team will support you in taking your medication as prescribed so that you will gain the maximum benefit.

Fulvestrant is an oestrogen receptor down-regulator and can be used in oestrogen receptor-positive, HER2-negative, post-menopausal, metastatic breast cancer. It can be used alone or in combination with palbociclib. It is given monthly by injection into the muscle. Fulvestrant has been funded in New Zealand since 2020.