Hormone Therapy for Breast Cancer | Breast Cancer
Treatment
Some types of breast cancer are affected by hormones, like estrogen and progesterone. The
breast cancer cells have receptors (proteins) that attach to estrogen and progesterone, which
helps them grow. Treatments that stop these hormones from attaching to these receptors are
called hormone or endocrine therapy.
Hormone therapy can reach cancer cells almost anywhere in the body and not just in the breast.
It's recommended for women with tumors that are hormone receptor-positive. It does not help
women whose tumors don't have hormone receptors (these tumors are called hormone receptor-
negative).
When is hormone therapy used for breast cancer?
Hormone therapy is often used after surgery (as adjuvant therapy) to help reduce the risk of the
cancer coming back. Sometimes it is started before surgery (as neoadjuvant therapy).
It is usually taken for at least 5 years. Treatment longer than 5 years might be offered to women
whose cancers have a higher chance of coming back. A test called the Breast Cancer Index might
be used to help decide if a woman will benefit from more than 5 years of hormone therapy.
Hormone therapy can also be used to treat cancer that has come back after treatment or that has
spread to other parts of the body.
How does hormone therapy work?
About 2 out of 3 breast cancers are hormone receptor-positive. Their cells have receptors
(proteins) for estrogen (ER-positive cancers) and/or progesterone (PR-positive cancers) which
help the cancer cells grow and spread.
There are several types of hormone therapy for breast cancer. Most types of hormone therapy
either lower estrogen levels in the body or stop estrogen from helping breast cancer cells grow.
Drugs that block estrogen receptors
These drugs work by stopping estrogen from fueling breast cancer cells to grow.
Selective estrogen receptor modulators (SERMs)
These drugs block estrogen from connecting to the cancer cells and telling them to grow and
divide. While they have anti-estrogen effects in breast cells, they act like an estrogen in other
tissues, like the uterus and the bones.
These drugs are pills, taken by mouth.
Tamoxifen
Tamoxifen can be used to treat women with breast cancer who have or have not gone through
menopause.
This drug can be used in several ways:
In women at high risk of breast cancer, tamoxifen can be used to help lower the risk of
developing breast cancer.
For women who have been treated with breast-conserving surgery for ductal carcinoma in
situ (DCIS) that is hormone receptor-positive, taking tamoxifen for 5 years lowers the
chance of the DCIS coming back in the same breast. It also lowers the chance of getting an
invasive breast cancer or another DCIS in both breasts.
For women with hormone receptor-positive invasive breast cancer treated with surgery,
tamoxifen can help lower the chances of the cancer coming back and improve the chances
of living longer. It can also lower the risk of a new cancer developing in the other breast.
Tamoxifen can be started either after surgery (adjuvant therapy) or before surgery
(neoadjuvant therapy). When given after surgery, it is usually taken for 5 to 10 years. This
drug is used mainly for women with early-stage breast cancer who have not yet gone
through menopause. If you have gone through menopause, aromatase inhibitors (see below)
are often used instead.
For women with hormone-positive breast cancer that has spread to other parts of the body,
tamoxifen can often help slow or stop the growth of the cancer, and might even shrink some
tumors.
Toremifene (Fareston)
Toremifene is a SERM that works in a similar way, but it is used less often and is only approved
to treat post-menopausal women with metastatic breast cancer. It is not likely to work if
tamoxifen has already been used and has stopped working.
Side effects of tamoxifen and toremifene
The most common side effects of tamoxifen and toremifene are:
Hot flashes
Vaginal dryness or discharge
Changes in the menstrual cycle
When tamoxifen treatment starts, a small number of women with cancer that has spread to the
bones might have a tumor flare (the tumor gets bigger for a short time) which can cause bone
pain. This usually goes away quickly, but rarely a woman may also develop a high calcium level
in the blood that is hard to control. If this happens, the treatment may need to be stopped for a
time.
Rare, but more serious side effects are also possible:
If a woman has gone through menopause, SERMs can increase her risk of developing
endometrial cancer and uterine sarcoma. Tell your doctor right away about any unusual
vaginal bleeding (a common symptom of this cancer). Most uterine bleeding is not from
cancer, but this symptom always needs quick attention.
Blood clots are another uncommon, but serious side effect. They usually form in the legs
(called deep vein thrombosis or DVT), but sometimes a piece of clot in the leg may break
off and end up blocking an artery in the lungs (pulmonary embolism or PE). Call your
doctor or nurse right away if you develop pain, redness, or swelling in your lower leg (calf),
shortness of breath, or chest pain, because these can be symptoms of a DVT or PE. Rarely,
tamoxifen has been associated with strokes in postmenopausal women, so tell your doctor
if you have severe headaches, confusion, or trouble speaking or moving.
Eye problems such as cataracts can sometimes happen when taking tamoxifen. It is
important to tell your doctor right away if you are having any new trouble with your
eyesight.
Bones can be affected. Depending on a woman's menopausal status, tamoxifen can have
different effects on the bones. In pre-menopausal women, tamoxifen can cause some bone
thinning, but in post-menopausal women it often strengthens bones to some degree. The
benefits of taking these drugs outweigh the risks for almost all women with hormone
receptor-positive breast cancer.
Selective estrogen receptor degraders (SERDs)
Like SERMs, these drugs attach to estrogen receptors. But SERDs bind to the receptors more
tightly and cause them to be broken down. These drugs have anti-estrogen effects throughout the
body.
SERDs are used most often in women who are past menopause. When given to pre-menopausal
women, they need to be combined with a luteinizing-hormone releasing hormone (LHRH)
agonist to turn off the ovaries (see Ovarian suppression below).
Fulvestrant (Faslodex)
Fulvestrant can be used:
Alone to treat advanced breast cancer that has not been treated with other hormone therapy.
Alone to treat advanced breast cancer after other hormone drugs (like tamoxifen and often
an aromatase inhibitor) have stopped working.
In combination with a CDK 4/6 inhibitor or PI3K inhibitor to treat metastatic breast cancer
as initial hormone therapy or after other hormone treatments have been tried.
It is given as 2 injections into the buttocks (bottom). For the first month, the 2 shots are given 2
weeks apart. After that, they are given once a month.
Elacestrant (Orserdu)
This drug can be used to treat advanced, ER-positive, HER2-negative breast cancer when the
cancer cells have an ESR1 gene mutation, and the cancer has grown after at least one other type
of hormone therapy.
Elacestrant is taken daily as pills.
Side effects of fulvestrant and elacestrant
Common short-term side effects of these drugs can include:
Hot flashes and/or night sweats
Headache
Nausea
Feeling tired
Loss of appetite
Muscle, joint, or bone pain
Injection site pain
Elacestrant can also increase cholesterol and fat levels in the blood.
Drugs that lower estrogen levels
Because estrogen stimulates hormone receptor-positive breast cancers to grow, lowering the
estrogen level can help slow the cancer’s growth or help prevent it from coming back.
Aromatase inhibitors (AIs)
Aromatase inhibitors (AIs) are drugs that stop most estrogen production in the body. Before
menopause, most estrogen is made by the ovaries. But in women whose ovaries aren’t working,
either because they have gone through menopause or because of certain treatments, estrogen is
still made in body fat by an enzyme called aromatase. AIs work by preventing aromatase from
making estrogen.
These drugs are useful for women who have gone through menopause, although they can also be
used in pre-menopausal women when they are combined with ovarian suppression (see below).
These AIs are pills taken every day to treat breast cancer:
Letrozole (Femara)
Anastrozole (Arimidex)
Exemestane (Aromasin)
Possible side effects of AIs
The most common side effects of AIs are:
Hot flashes
Vaginal dryness
Bone and joint pain
Muscle pain
AIs tend to have side effects different from tamoxifen. They don't cause uterine cancers and very
rarely cause blood clots. They can, however, cause muscle pain and joint stiffness and/or pain.
The joint pain may be similar to a feeling of having arthritis in many different joints at one time.
Options for treating this side effect include, stopping the AI and then switching to a different AI,
taking a medicine called duloxetine (Cymbalta), or routine exercise with nonsteroidal anti-
inflammatory drugs (NSAIDs). But the muscle and joint pain has led some women to stop
treatment. If this happens, most doctors recommend using tamoxifen to complete 5 to 10 years of
hormone treatment.
Because AIs drastically lower the estrogen level in women after menopause, they can also cause
bone thinning, sometimes leading to osteoporosis and even fractures. If you are taking an AI,
your bone density may be tested regularly and you may also be given bisphosphonates
(zoledronic acid [Zometa] for example) or denosumab (Xgeva, Prolia), to strengthen your bones.
Ovarian suppression
For pre-menopausal women, removing or shutting down the ovaries (ovarian suppression),
which are the main source of estrogen, is effectively making them post-menopausal. This may
allow some other hormone therapies, such as AIs, to be used. Ovarian suppression along with
tamoxifen or an AI might be recommended for women whose breast cancer is at high risk of
coming back.
There are several ways to remove or shut down the ovaries to treat breast cancer:
Oophorectomy: Surgery to remove the ovaries. This is permanent and is also called
ovarian ablation.
Luteinizing hormone-releasing hormone (LHRH) agonists: These drugs, also called
LHRH analogs, are used more often than oophorectomy. They stop the signal that the body
sends to the ovaries to make estrogen, which causes temporary menopause. Common
LHRH drugs include goserelin (Zoladex) and leuprolide (Lupron). They can be used alone
or with other hormone drugs (tamoxifen, aromatase inhibitors, fulvestrant) as hormone
therapy in pre-menopausal women.
Chemotherapy drugs: Some chemo drugs can damage the ovaries of pre-menopausal
women so they no longer make estrogen. Ovarian function can return months or years later
in some women, but in others the damage to the ovaries is permanent and leads to
menopause.
All of these methods can cause symptoms of menopause, including hot flashes, night sweats,
vaginal dryness, and mood swings.
Hormone therapy after surgery for breast cancer
After surgery for treatment of hormone receptor-positive breast cancer, hormone therapy can be
given to reduce the risk of the cancer coming back.
These hormone therapy schedules are known to be helpful for women who are post-menopausal
when diagnosed:
An AI for 5 to 10 years
An AI for 2 to 3 years, followed by tamoxifen for 2 to 3 years (5 years total of treatment)
Tamoxifen for 2 to 3 years, followed by an AI for 2 to 3 years (5 years total of treatment)
Tamoxifen for 2 to 3 years, followed by an AI for 5 years (7 to 8 years of treatment)
Tamoxifen for 4½ to 6 years, followed by an AI for 5 years (9½ to 11 years of treatment)
Tamoxifen for 5 to 10 years
For women who are unable to take an AI, tamoxifen for 5 to 10 years is an option
An AI along with ribociclib (Kisqali) for 3 years followed by AI alone to complete 5 years.
For most post-menopausal women whose cancers are hormone receptor-positive, most doctors
recommend taking an AI at some point during adjuvant (after surgery) therapy. Standard
treatment is to take these drugs for about 5 years, or to take in sequence with tamoxifen for 5 to
10 years. For women at a higher risk of recurrence, hormone treatment for longer than 5 years
may be recommended. Tamoxifen is an option for some women who cannot take an AI. Taking
tamoxifen for 10 years is considered more effective than taking it for 5 years, but you and your
doctor will decide the best schedule of treatment for you.
These therapy schedules are known to be helpful for women who are pre-menopausal when
diagnosed:
Tamoxifen (with or without ovarian suppression) for 5 to 10 years.
Tamoxifen (with or without ovarian suppression) for 5 years followed by an AI for 5 years
if you have gone through menopause.
An AI plus ovarian suppression for 5 to 10 years.
An AI plus ovarian suppression, along with ribociclib (Kisqali) for 3 years followed by AI
alone to complete 5 years.
If you have early-stage breast cancer and had not gone through menopause when you were first
diagnosed, your doctor might recommend taking tamoxifen first, and then taking an AI later if
you go through menopause during treatment. Another option is ovarian suppression (see above)
by using a medication that can turn off the ovaries, along with an AI. Pre-menopausal women
should not take an AI alone for breast cancer treatment because it is unsafe and can
increase hormone levels.
If cancer comes back or has spread
Tamoxifen, AIs, elacestrant, and fulvestrant can be used to treat more advanced hormone-
positive breast cancers, especially in post-menopausal women. They are often continued for as
long as they are helpful. Pre-menopausal women might be offered tamoxifen alone or an AI in
combination with an LHRH agonist for advanced disease.
Less common types of hormone therapy
Some other types of hormone therapy that were used more often in the past, but are rarely given
now include:
Megestrol acetate (Megace), a progesterone-like drug
Androgens (male hormones), like testosterone
Estradiol (a form of estrogen)
These might be options if other forms of hormone therapy are no longer working, but they can
often cause side effects.
