Hormone therapy

The development of breast cancer is often influenced by certain hormones in the body such as estrogen and progesterone. Estrogen and progesterone are the hormones responsible for, among other things, female attributes at puberty and the menstrual cycle. They are mainly produced by the ovaries. To produce estrogen, the ovaries must be stimulated by other hormones: FSH and LH. FSH and LH are produced by the pituitary gland under the influence of the hypothalamus. (The pituitary gland and hypothalamus are two small glands located in the brain). 

Before proposing hormone therapy for breast cancer, the oncologist makes sure that the treatment will be effective. To determine this, a careful analysis is performed on cancer cells taken during the biopsy or removed during surgery. This analysis will verify, among other things, whether proteins called hormone receptors are present. Breast cancer cells may have receptors for estrogen (ER+), progesterone (PR+) or both. When a cancer cell has this type of receptor, the presence of the hormone can promote its growth. The analysis can determine whether or not each type of hormone receptor (estrogen and progesterone) is present and how much of each is present in the cancer cell.

Hormone therapy will be indicated only if the breast cancer hormone receptors are positive. The treatment consists of taking a medication that blocks hormone production, or blocks its action. It is most often taken orally.

More than two-thirds of all breast cancers contain estrogen and/or progesterone receptors. They are known as hormone-dependent cancers.
 

Objectives of hormone therapy 

• To reduce the risk of hormone-dependent, non-invasive (in situ) breast cancer developing into invasive breast cancer;
• To reduce the risk of recurrence of hormone-dependent invasive breast cancer;
• To shrink a large hormone-dependent breast tumour prior to surgery;
• To treat hormone-dependent breast cancer that is advanced locally or has recurred;
• To relieve the pain or control the symptoms of hormone-dependent advanced or metastatic breast cancer.

Factors influencing the choice of hormone therapy and duration of treatment:

• Medical history;
• Menopausal status (menopausal or not);
• Stage and grade of cancer;
• Risk of relapse.             

Hormonal therapy may sometimes be combined with a cell cycle inhibitor (a drug that prevents cells from multiplying) in the treatment of advanced or metastatic hormone-dependent breast cancer.

The type of medication, the dose prescribed, its combination with another drug and the duration of treatment are adapted to each situation.
 

Advantages of hormone therapy

• Treatment known to be effective in reducing the risk of breast cancer recurrence;
• Acts on both local and metastatic breast cancer;
• Can be administered together with other treatments to enhance their effectiveness (advanced or recurrent cancers);
• Relieves some of the symptoms of advanced breast cancer.

  Disadvantages of hormone therapy

• May have side effects impacting quality of life;
• Some side effects are permanent.  

Types of treatments

The majority of hormonal treatments consist of medication. The two most common types of drugs used to treat breast cancer are anti-estrogens and aromatase inhibitors.
 

Anti-estrogens

These are drugs that bind directly to estrogen receptors on cancer cells. They block these receptors to prevent the cancer cells from utilizing estrogen.

• Tamoxifen

Tamoxifen (Nolvadex, Tamofen) is the most commonly used anti-estrogen medication. It is the drug of choice for non-menopausal women. It is also frequently prescribed for postmenopausal women.

Tamoxifen slightly increases the risk of endometrial cancer, deep vein thrombosis (DVT) and stroke. For this reason, oncologists need to assess the risks and benefits of this drug before offering it to women who have a personal or significant family history of these conditions.

• Fulvestrant

Fulvestrant (Faslodex) is injected intramuscularly and is used to treat postmenopausal women whose breast cancer has progressed after tamoxifen therapy. It is also prescribed for postmenopausal women with locally advanced or metastatic breast cancer that has never been treated with hormonal therapy.

Aromatase Inhibitors

Aromatase is an enzyme that allows estrogen to be produced by organs other than the ovaries, such as fatty tissue and the adrenal glands. Aromatase inhibitors are drugs that prevent the production of aromatase or block its action, resulting in decreased estrogen levels in the body.

Aromatase inhibitors are prescribed only to postmenopausal women. They are not effective in non-menopausal women because they do not act on the ovaries, where most estrogen is produced prior to menopause.

These drugs are administered orally.

The most commonly prescribed medications for the treatment of hormone-dependent breast cancer are:

• Letrozole (Femara);
• Anastrozole (Arimidex);
• Exemestane (Aromasin).

This class of drugs can cause or increase loss of bone density (osteoporosis). Therefore, women receiving an aromatase inhibitor should also receive vitamin D and calcium supplements. Bone density and risk of fracture should be monitored periodically. For example, women should usually undergo a bone density test (bone densitometry) before starting treatment. These examinations need to be repeated and monitored on a regular basis, especially for women whose personal or family medical history puts them at risk of developing osteoporosis.
 

Luteinizing hormone-releasing hormone (LHRH) analogs

LH-RH agonists (or analogs) are drugs that stop the ovaries producing estrogen. They are prescribed only to non-menopausal women. They bring about temporary menopause. They are injected subcutaneously over a 3- to 5-year period:

• Goserelin (Zoladex);
• Leuprolide (Lupron, Lupron Depot, Eligard);
• Buserelin (Suprefact).

This drug may sometimes be used in combination with tamoxifen or an aromatase inhibitor in women who have not yet reached menopause following chemotherapy, such as young women under 35 years of age or those with cancer that has spread to the nodes.
 

Non-drug treatments

A non-drug hormone therapy treatment may be used in premenopausal women. This consists of direct intervention on the ovaries to suppress estrogen production:

• Surgical removal of the ovaries (oophorectomy) is the preferred treatment for older, premenopausal women who no longer want children.
• Radiotherapy is rarely used for this purpose, but may be proposed for women who cannot be operated upon.

These treatments result in permanent, irreversible menopause.  

Treatment based on menopausal status

• Hormone therapy for non-menopausal women

The drug of choice for women with hormone-dependent breast cancer is tamoxifen, which is prescribed for a period of 5 to 10 years.

After 5 years, the drug can sometimes be stopped, but depending on the type of cancer and its risk of recurrence, the treatment can be extended for another 5 years.

If treatment needs to be prolonged, tamoxifen will be re-prescribed to women who are not postmenopausal. If they reach menopause in the meantime, the oncologist may continue tamoxifen or switch to an aromatase inhibitor.
 

• Hormone therapy for postmenopausal women

The hormone therapy prescribed to postmenopausal women is either tamoxifen or an aromatase inhibitor for a period of 5 to 10 years.

Oncologists may adopt different approaches in deciding the medication best suited to the individual's condition. Sometimes a single medication is used for 10 years and sometimes there is alternation between medications.

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IMPORTANT!

Advanced endometrial and ovarian cancers can also be treated with the various hormone therapies described above, either alone or in combination with another treatment.

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Sources

Anti-Hormonal Therapy and Breast Cancer
Hormonal therapy for breast cancer
Hormone Therapy for Breast Cancer
Hormonal therapy
VERZENIO™ (abemaciclib) available in Canada for metastatic breast cancer

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Prostate cancer cells are hormone-dependent. This means that their growth is influenced by the presence of the male hormones known as androgens. Androgens are hormones that are responsible for the development of masculine physical characteristics, such as the voice breaking and the appearance of facial and body hair at puberty. The main androgens are testosterone and dihydrotestosterone (DHT). They are produced by the testes under the influence of LHRH secreted by the hypothalamus.

Hormonal therapy for prostate cancer aims at blocking the action of these hormones. It is also called androgen deprivation therapy or anti-androgen therapy or chemical or surgical castration. It is mainly used to treat advanced, recurrent or aggressive (“high-grade”) prostate cancer.

Objectives of hormone therapy

• To reduce the size of the tumour prior to radiotherapy (neoadjuvant treatment);
• To improve the effectiveness of treatment during radiotherapy;
• To reduce the risk of cancer progression following radiotherapy or surgery (adjuvant treatment);
• To relieve pain or decrease symptoms of advanced prostate cancer (palliative treatment).  

The oncologist first assesses the overall health of the person, as well as the type, stage and grade of the cancer and his PSA (Prostate Specific Antigen) level (PSA is an enzyme produced by the prostate gland). He then decides whether hormone therapy is indicated and what form it should take.

Hormone therapy is effective in slowing the growth of prostate cancer, but does not cure it. The length of its effectiveness varies greatly from person to person. Among the men who take it, 70-85% respond well to treatment for periods varying from 1 to over 10 years.  

Hormone therapy can be administered continuously (without interruption) or intermittently (periodically).

Indications for intermittent hormone therapy

• Delaying onset of resistance to hormone therapy (hormone resistance);
• Improving tolerance to treatment;

This method of administering hormone therapy makes it possible to stop the treatment after a variable period of time or as soon as the PSA level drops sufficiently. When PSA levels rise again, the hormone therapy is resumed and can be stopped again temporarily if PSA normalizes. This leads to better tolerance to treatment and a better quality of life.

Advantages of hormone therapy

• Although it is not a cure, it is a recognized, effective treatment for prostate cancer;
• It acts on prostate cancer wherever it occurs in the body (metastases);
• It can be administered in combination with other treatments to make them more effective;
• It can lessen some of the symptoms of advanced prostate cancer.  

Disadvantages of hormone therapy

• May cause side effects affecting quality of life;
• Some side effects are permanent;
• Its effectiveness is of limited duration and varies according to the patient (resistance to hormone therapy).  

Types of treatment

There are three main types of hormone therapy for prostate cancer:

• Injections or implants to block the production of testosterone (chemical castration);
• Tablets to block the effects of testosterone;
• Surgery to remove the testicles (surgical castration).

The most frequently used types of hormone therapy

• Androgen deprivation with luteinizing hormone-releasing hormone (LHRH) analogs or antagonists;
• Anti-androgens;
• Surgery. 

Androgen deprivation with luteinizing hormone-releasing hormone (LHRH) analogs or antagonists

LHRH is a hormone produced by the hypothalamus at the base of the brain. This hormone controls the secretion of sex hormones. LHRH analogs (or agonists) and antagonists are drugs designed to block the production of testosterone by the testes (chemical castration) by acting on the production of LHRH. Decreased testosterone levels slow the growth of prostate cancer cells.
 
The most frequently used LHRH analogs are:

• Leuprolide (Lupron, Lupron Depot, Eligard);
• Goserelin (Zoladex);
• Triptorelin (Trelstar);
• Buserelin (Suprefact).

These drugs are given by regular injections administered at variable intervals depending on the drug chosen. For example, the injection can be given once a month, or every 3, 4 or 6 months. The treatment can be given continuously or intermittently.

The LHRH antagonist used to treat prostate cancer is Degarelix (Firmagon). It is given by injection once a month.

Blood samples are usually prescribed to monitor testosterone levels. This ensures that hormone suppression is effective.

The anti-androgens

Anti-androgens stop the production of androgens or block their action. They bind to androgen receptors on prostate cancer cells and prevent them from using testosterone to grow.

Anti-androgens are generally not used alone to treat prostate cancer. As the primary treatment for prostate cancer, they may be combined with surgical castration or an LHRH (combined androgen blockade) antagonist.

They are also often combined with LHRH agonists or analogs for a short period of time to mitigate a temporary tumor outbreak reaction to these drugs at the outset of administration.

Anti-androgens can be taken orally in tablet or liquid form.

• As the sole treatment (rarely) (metastatic prostate cancer);
• As part of a combined treatment prior to starting injections or implants;
• As part of a combined treatment at the same time as injections or implants;
• After surgery to remove the testicles (surgical castration).

The most common types are:

• Bicalutamide (Casodex);
• Flutamide (Euflex);
• Cyproterone Acetate (Androcur);
• Nilutamide (Anandron);
• Abiasterone Acetate (Zytiga) combined with Prednisone;
• Enzalutamide (Xtandi).

Surgery

Surgical hormone treatment for prostate cancer consists of removing the testicles. It is sometimes called surgical castration. Removing the testicles decreases the amount of testosterone in the body, which reduces the progression of most prostate cancers.

It is a radical treatment since testosterone concentration can drop by 90 to 95%. This procedure is performed as day surgery under regional anesthesia.

Two techniques can be used:

• Pulpectomy: preserves the external wall of the testicles;
• Orchiectomy: the entire testicle is removed. 

Sources

Hormone therapy
Hormonal therapy for prostate cancer
Hormone Therapy for Prostate Cancer
 

Corticosteroids

Cortisol is the natural hormone secreted by the adrenal glands under the action of the hormone ACTH secreted by the pituitary gland. One of its roles is to limit inflammatory response.

Synthetic cortisol (manufactured in the laboratory) includes many drugs used in oncology for many cancers and for many indications including:
 

Initial treatment

• Corticosteroids are used for the treatment of hematological cancers such as leukemia, lymphoma, Hodgkin's disease and multiple myeloma in combination with chemotherapy and targeted therapy protocols.

Support treatment

• They are used to control the symptoms associated with cancer, its treatment and its progression;
• Other uses include being sometimes prescribed as an emergency treatment for hypercalcemia or compressions caused by the presence of metastases, mainly of the bone and brain.

Treatment in combination with chemotherapy

• To increase its efficiency;
• To prevent side effects such as nausea and vomiting.

Main types of synthetic corticosteroids (drugs)

• Prednisone;
• Dexamethasone (Decadron, Dexasone);
• Hydrocortisone;
• Methylprednisone (Medrol).

Thyroid hormone

Thyroid-stimulating hormone (TSH), is secreted into the bloodstream by the pituitary gland; its purpose is to stimulate the thyroid gland, which produces two hormones:

• the triiodothyronine or T3;
• the tetraiodothyronine or thyroxine, or T4.

Hormone therapy is required for everyone who undergoes a total thyroidectomy (complete removal of the thyroid gland) for thyroid cancer.

Several types of thyroid cancer are hormone-dependent. This means that thyroid hormones promote the growth of tumour cells. Hormonal treatment is therefore an indispensable treatment following surgery (resection of the thyroid gland) and radiotherapy with radioactive iodine (iodine 131).

This hormonal treatment consists of taking synthetic thyroid hormones in the form of a drug: levothyroxine or Synthroid.

There are two objectives, depending on the doses of medication used:

• At normal doses, treatment replaces the action of the thyroid and aims at maintaining a normal level of TSH (the pituitary hormone that regulates the thyroid gland): this is known as hormone replacement therapy.
• At high doses, it acts to prevent the secretion of TSH that could stimulate remaining tumour cells: this is known as antihormonal therapy.

Levothyroxine replaces the natural hormones that were produced by the thyroid gland prior to removal during surgery. It must be taken for life; precise blood monitoring and control are required to ensure the correct dosage.

Somatostatin analogs

These are drugs designed to lower the level of hormones produced and released by neuroendocrine tumours (NETs).

Neuroendocrine or carcinoid tumours are benign or malignant tumours that typically develop in the digestive tract. They can also affect the pancreas, lungs and more rarely, the testes or ovaries. They are slow-growing tumours. Because they can produce high levels of hormonal substances, these tumours can sometimes cause a carcinoid syndrome.

Carcinoid syndrome consists of a combination of symptoms such as hot flashes, abdominal cramps, and heart and lung problems.

The symptoms of carcinoid syndrome are controlled or prevented with the use of a somatostatin analog. The medication most commonly used is called octreotide (Sandostatin, Sandostatin LAR). It is available in 2 forms, fast-acting or long-acting, and is administered by intramuscular injection.

Progestin

Synthetic progestin is the major type of hormone therapy used to treat cancer of the endometrium (the inner lining of the body of the uterus). Endometrial cancer is a hormone-dependent cancer because the secretion of estrogen by the adrenal glands after menopause influences its development and growth. On the other hand, progesterone has a protective effect. Progestin is a drug that acts like progesterone (female hormone) and slows down the growth of endometrial cancer cells.

The following progestins are used to treat endometrial carcinoma and advanced or metastatic sarcoma of the uterus. They are administered either in daily doses, taken orally, or in the form of a long-acting injection. These drugs are called:

• Medroxyprogesterone (Provera);
• Megestrol (Megace, Apo-megestrol, Nu-megestrol, Lin-megestrol).

Other drugs already described in this column may also be given to treat advanced endometrial cancer: anti-estrogens, LHRH agonists and aromatase inhibitors.