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Hormone Therapy

Hormone (or endocrine) therapy is the treatment of cancer with medication that blocks the production of the hormoneHormone:
A natural substance released into the body by the endocrine glands, such as the thyroid, adrenal gland or ovaries.
estrogenEstrogen:
A female sex hormone that is produced mainly in the ovaries. A woman’s levels of estrogen fluctuate throughout her life. Estrogen has been linked to the development of breast cancer and may promote the growth of cancer cells.
, or the way it works in the body. Hormone therapy is a systemic treatmentSystemic treatment:
A treatment method that is applied to and takes effect in the entire body. Chemotherapy, hormone therapy and HER-2 targeted therapy are systemic treatments for breast cancer.
for breast cancer because it acts on the whole body. It can be taken by mouth or as an injection under the skin or into a muscle.

Estrogen is a naturally occurring hormone in the human body that plays an important role in the female reproductive system. Estrogen also influences the development and growth of breast cancer.

Hormone therapy is most often given after surgery, radiation therapyRadiation therapy (Sometimes called radiotherapy):
A treatment method that uses a high energy beam to destroy cancer cells by damaging the DNA of cancer cells so that they can’t continue to grow.
and chemotherapyChemotherapy:
A treatment method that uses medication to destroy cancer cells.
. The goal of hormone therapy is to block estrogen from stimulating the growth of some breast cancers. The therapy also helps to reduce the risk of recurrenceRecurrence:
Cancer that returns after treatment.
(the cancer coming back). For some women, it may be given before surgery to shrink the size of the tumourTumour:
An abnormal mass of tissue that occurs when cells divide more than they should or do not die when they should. Tumours may be benign (not cancer) or malignant (cancer). A tumour is also called a neoplasm.
. It may also be used to treat advanced breast cancer to try to shrink or slow the growth of the tumour.

Estrogen receptor-positive breast cancer

In some people with breast cancer, the presence of estrogen promotes cancer cellCell:
The basic structural and functional unit of all organisms.
growth. Estrogen attaches to the surface of a cancer cell at special points called receptors and speeds up the growth of that cell. These cancers are known as estrogen receptor positive (ER positive) because the cancer growth is fueled by estrogen. Approximately 65-75% of breast cancers are estrogen receptor positive.  If the effect of estrogen on these cells can be stopped, the cancer growth is slowed down. Hormone therapy can help to do this.

Estrogen receptor-negative breast cancer

In other people, the breast cancer cell growth rate is not affected by the presence of estrogen. These cancers are known as estrogen receptor negative (ER negative). For patients whose cancers are estrogen receptor negative, there is likely no benefit from taking hormone therapy.

To find out the estrogen receptor status of breast cancer, cancer cells are tested in a lab. If they are found to be estrogen receptor-positive, then hormone therapy may help.

There are three different types of hormone therapy:

  • Anti-estrogens

  • Aromatase inhibitors

  • Ovarian suppression

Hormone Therapy: Anti-Estrogens

Anti-estrogens are a form of hormone therapy used to treat estrogen receptor positive breast cancers.

Anti-estrogens work by preventing estrogen from attaching to the estrogen receptors, which would otherwise promote cancer cell growth. The goal of anti-estrogens is to slow down cancer cell growth and reduce the risk of recurrence (cancer coming back).

Tamoxifen

The most common anti-estrogen medication is tamoxifen. It is taken by mouth as a pill, and can be used in the treatment of both early-stageStage:
A way of classifying breast cancer that describes how far a cancer has spread. It identifies whether breast cancer is at an early, locally advanced or metastatic stage. The stage of breast cancer can sometimes be represented as a number (e.g. between 0 and 4).
and metastaticMetastatic (metastases):
The spread of cancer from its original (primary) location to another part of the body. A tumour that is formed by cancer cells that have spread to another part of the body is called a “metastatic tumour” or a “metastasis.”
breast cancer. Both Pre-menopauseMenopause:
A natural part of a woman's aging process, when the ovaries start to make less estrogen and progesterone and the menstrual periods stop. This change typically occurs between the late 40s and mid-to-late 50s.
and postmenopausal women can benefit from tamoxifen, as can men with breast cancer. Tamoxifen can be taken for up to 5 years, though recent evidence suggests that there may be benefit to taking it longer, for up to 10 years.

Tamoxifen is used to reduce the risk of recurrence in women who have had breast cancer. It can also be used for breast cancer prevention in both premenopausal and postmenopausal women who are at high risk of developing breast cancer. It may also be used to treat advanced breast cancer to try to shrink or slow the growth of the tumour.

Side effects

Many of the side effects of tamoxifen result from how it influences the effects of estrogen in your body. Side effects of tamoxifen include hot flashes, night sweats, irregular periods, vaginal dischargeDischarge (vaginal):
Fluid produced by glands in the vaginal wall and cervix that drain from the opening of the vagina.
, and bladder problems in some women.

Premenopausal women may experience reduced fertility while taking tamoxifen, but fertility should return to normal if the treatment is stopped during the child-bearing years. For men, a potential side effect may be impotenceImpotence:
An inability to achieve or maintain an erection during sexual activity. It is also referred to as erectile dysfunction.
.

Rare side effects of tamoxifen include the following:

The small increase in risk for these rare side effects must be weighed against the significant benefits of anti-estrogens, including the reduced risk of breast cancer recurrence (cancer coming back).

Other anti-estrogen medications include fulvestrant and raloxifene. Raloxifene is also used to prevent breast cancer in high risk women who are postmenopausal. Raloxifene does not have the same estrogen-like effects on the uterus as tamoxifen, so the risk of endometrial cancer is lower with this drug.

Ask your health care team about the benefits, limitations and possible side effects of anti-estrogens to help you make an informed decision about your treatment.

Hormone Therapy: Aromatase Inhibitors

AromataseAromatase:
An enzyme that helps to produce estrogen in the body. Aromatase inhibitors are a type of hormone therapy that works by blocking the ability of aromatase to produce estrogen, which helps to slow the growth of estrogen-sensitive breast cancer.
inhibitors are a form of hormone therapy used in women who are postmenopausal to treat breast cancers that are stimulated by the presence of estrogen. They act by stopping the production of estrogen. Aromatase inhibitors are taken as a pill by mouth and can be used in the treatment of both early-stage and metastatic breast cancer.

Before reaching menopause, women produce most of their estrogen in the ovariesOvary:
A female reproductive organ in which ova or eggs are produced. The ovaries also produce the female hormones estrogen and progesterone.
. After menopause, most of the estrogen in a woman’s body is produced in fat and other tissues, not in the ovaries. Making estrogen outside of the ovaries relies on an enzymeEnzyme:
Proteins that are involved in carrying out the chemical reactions of the body.
in the body called aromatase.

Treatment

Aromatase inhibitors work by stopping the production of aromatase or blocking its actions, therefore reducing the amount of estrogen a postmenopausal woman can produce. If the overall level of estrogen is reduced, there is less available to bind to the estrogen receptors in breast cancer cells. This helps to slow the growth of estrogen-sensitive breast cancer. The most common aromatase inhibitors used are: letrozole (Femara), anastrozole (Arimidex), and exemestane (Aromasin).

Aromatase inhibitors can be the first hormone therapy drug prescribed, or can follow tamoxifen after 2-5 years of use to help reduce the risk of breast cancer recurrence. They are not used together with tamoxifen.

There are no studies that examine the effectiveness of aromatase inhibitors in men with breast cancer, but some men may benefit from this therapy.

Side effects

The side effects of aromatase inhibitors result from lowering the amount of estrogen in the body, similar to what happens during menopause.

Possible side effects of aromatase inhibitors include hot flashes, joint pain, muscle aches, and fatigue. There is also an increased risk for bone loss and osteoporosisOsteoporosis:
A condition where the amount and quality of bone in the body are reduced. It causes bones to become weak and brittle, making them more prone to fractures (broken bones).
(weakening of the bones). This occurs because estrogen normally helps to maintain bone density. Aromatase inhibitors have a lower risk of blood clots that some anti-estrogen drugs do, and they do not increase the risk of endometrial cancer.

Ask your health care team about the benefits, limitations and possible side effects of aromatase inhibitors to help you make an informed decision about your treatment.

Hormone Therapy: Ovarian Suppression

Ovarian suppression is used to treat estrogen receptor positive breast cancers in premenopausal women.

Before menopause, women produce most of their estrogen in the ovaries. For premenopausal women with estrogen receptor positive breast cancer, it may be beneficial to stop the ovaries from producing estrogen as a way of ‘starving’ the tumour of estrogen. With lower levels of estrogen in the body overall, there is less estrogen available to bind to the estrogen receptors in breast cancer cells. This helps to slow the growth of estrogen-sensitive breast cancer.

Ovarian suppression is used in cases where a woman chooses not to have chemotherapy or can’t have other breast cancer treatments. It may also be used to treat recurrent or metastatic breast cancer.

Treatment types and effects on fertility

Ovarian suppression (also called ovarian ablation) refers to any treatment given to stop the ovaries from producing estrogen. The treatment can be by surgery to remove the ovaries (called an oophorectomyOophorectomy:
Surgical removal of one or both ovaries.
), radiation treatment to the ovaries, or medication. These treatments put your body into early menopause.

It is important to note that surgery and radiation therapy suppress the ovaries permanently, and becoming pregnant will not be possible after these treatments. The effects of medication may be reversible, and pregnancy may be possible when treatment is complete.

Medications used to stop the ovaries from producing estrogen are called luteinizing hormone-releasing hormone (LHRH) agonists. They work by causing your brain to stop producing the hormone that tells your ovaries to produce estrogen. The most commonly used LHRH agonists are goserelin (Zoladex), leuprolide (Lupron, Lupron Depot, Eligard), and buserelin (Suprefact). They are given by an injection under the skin or into a muscle every month or every 3 months, depending on the drug. They are usually given for a period of 3-5 years.

The impact of treatment on fertility is a common concern for women who are diagnosed with breast cancer during their child-bearing years. The risk of infertilityInfertility:
The inability to produce a child. In women, this can mean an inability to conceive or carry a child to term. In men, this refers to the inability to impregnate a woman.
can bring up many emotions and may feel overwhelming, at a time when you may still be adjusting to your breast cancer diagnosis and considering your treatment options and the possible effects of those decisions. Even if having children isn’t important to you now, it may become important to you later. Discuss your fertility with your health care team so that it can be taken into consideration when planning your treatment. If your fertility may be impacted, you may have the option of having embryosEmbryo:
A fertilized egg in the early stages of development.
or unfertilized eggs frozen to use in fertility treatments at a later time.

Ask your health care team about the benefits, limitations and possible side effects of ovarian suppression, including their effect on fertility, to help you make an informed decision about your treatment.

Resistance to Hormone Therapy

It is possible for cancer cells to withstand the effects of hormone therapy medications, such as tamoxifen and other drugs. This is known as drug resistance. Resistance to a hormone therapy drug can be present from the beginning, but often develops during the course of the treatment.

Tumours which develop resistance to a hormone therapy drug can make it more difficult to plan treatment because the drug options become more limited. Research is currently looking into ways to overcome resistance to hormone therapy drugs.


Sources:

American Cancer Society. Hormone therapy for breast cancer. Accessed January 10, 2014.

American Cancer Society. Medicines to reduce breast cancer risk: Tamoxifen and raloxifene​. Accessed January 10, 2014.

American Cancer Society. Study: Ten Years of Tamoxifen Better than Five. Accessed January 10, 2014.

Breastcancer.org. Aromatase inhibitors. Accessed January 10, 2014.

Breastcancer.org. Fertility and Pregnancy Issues During and After Breast Cancer. Accessed January 10, 2014.

Breastcancer.org. Options if You Can’t Get Pregnant After Treatment. Accessed January 10, 2014.

Canadian Cancer Society. Hormonal therapy for breast cancer. Accessed January 10, 2014.

National Cancer Institute. Hormone Therapy for Breast Cancer. Accessed January 10, 2014.