Tamoxifen

Tamoxifen is a form of hormonal therapy used to treat hormone receptor-positive breast cancer, or to reduce the risk of developing this type of cancer. Tamoxifen can be given:

• To reduce the risk of developing breast cancer
  • This includes reducing risk of hormone receptor-positive ductal carcinoma in situ (DCIS), also known as stage 0 breast cancer, becoming invasive breast cancer
  • Tamoxifen can also reduce the risk of developing cancer in the other breast.
• To reduce the risk that hormone receptor-positive, early-stage breast cancer will come back (recur) after surgery
• To shrink the size of a hormone receptor-positive breast cancer before surgery
• To treat hormone receptor-positive metastatic breast cancer, slowing or stopping its growth
• To lower the risk of breast cancer in people who’ve never been diagnosed but have a higher-than-average risk for developing it

Tamoxifen is part of a class of medicines known as SERMs, or selective estrogen receptor modulators. SERMs are sometimes called estrogen blockers. This is because SERMs attach to the estrogen receptors on breast cancer cells and block estrogen from signaling them to grow. Blocking estrogen can slow or stop the growth of hormone receptor-positive breast cancer.

Tamoxifen cannot be used to treat hormone receptor-negative breast cancer.

When is tamoxifen given?

Tamoxifen may be given to treat hormone receptor-positive breast cancer, and/or reduce the risk of a future cancer, depending on your situation. It can be given:

• After surgery for early-stage breast cancer (this is called adjuvant treatment)
• Before surgery, to reduce the size of the cancer (neoadjuvant treatment) and possibly allow for a smaller operation
• At any time after a metastatic breast cancer diagnosis
• At any time for a person who has an increased risk of developing breast cancer but has never been diagnosed

Who gets tamoxifen?

Tamoxifen can be used to treat breast cancer in women and men.

• Most men take tamoxifen by itself.
• Most postmenopausal women (women who have not had a menstrual period for 12 months or more) can also take tamoxifen by itself.
• Premenopausal and perimenopausal women, who are still having a menstrual cycle, can either take tamoxifen alone or along with another medicine that reduces how much estrogen the ovaries make.

Tamoxifen and menopausal status

Tamoxifen is approved for use by women of any menopausal status.

• Premenopausal and perimenopausal women are still having a menstrual cycle, so their ovaries are still producing high levels of estrogen.
• Postmenopausal women have gone 12 months or more without having their period, so their ovaries are no longer producing estrogen and their levels are much lower.

Taking tamoxifen or other hormonal therapy with ovarian suppression medicine

For premenopausal and perimenopausal women, tamoxifen is sometimes used alone. However, it’s often combined with another medicine that stops the ovaries from making estrogen to lower estrogen levels even more. You and your healthcare team may decide to combine medicines if the breast cancer has a high risk of recurrence. Risk factors for recurrence include:

• Younger age
• Having cancer in the lymph nodes
• Having a higher-grade cancer (fast-growing breast cancer cells that look very different from normal breast cells)

Medicines that slow down ovarian function are called gonadotropin-releasing hormone (GnRH) agonists (sometimes also called luteinizing hormone-releasing hormone agonists, or LHRH agonists). They are also sometimes called ovarian function suppressors.

How GnRH agonists work:

• GnRH agonists send a message to the brain that stops the ovaries from producing estrogen.
• This puts a premenopausal or perimenopausal woman into menopause for as long as she is receiving the medicine, which further lowers her estrogen levels.
• Combining tamoxifen with a GnRH agonist can do even more to slow the growth of high-risk hormone receptor-positive breast cancer than giving tamoxifen alone.

In some cases, doctors may recommend a different type of hormonal therapy called an aromatase inhibitor. This type of hormonal therapy can also be given in combination with a GnRH agonist.

In premenopausal women with early-stage breast cancer, research shows that adding a GnRH agonist to tamoxifen or an aromatase inhibitor helps some women live longer without a recurrence. However, adding this medicine to hormonal therapy can increase side effects. It’s important to talk with your healthcare team about what’s right for you.

Whatever your menopausal status, your team will work with you to make decisions about hormonal therapy. The type of hormonal therapy is based on your risk of recurrence and whether you have been diagnosed with early-stage or metastatic breast cancer.

Tamoxifen and pregnancy

It’s important to know that it is not safe to get pregnant while taking tamoxifen or aromatase inhibitors, because these medicines can harm an unborn baby.

However, a clinical trial called POSITIVE showed it’s safe for women with early-stage, hormone receptor-positive breast cancer to pause hormonal therapy if they want to get pregnant. In the trial, stopping therapy temporarily did not increase the risk of recurrence.

Follow-up results showed that extending the break to breastfeed did not increase recurrence risk. Still, longer-term follow-up is needed to track how long the women in the study remain recurrence-free, and how these numbers compare to women who don’t take a break from hormonal therapy.

Learn about one woman’s experience with pausing tamoxifen to have a baby.

How is tamoxifen given?

Tamoxifen is taken daily as a pill and should be swallowed whole.

Tamoxifen comes in 10-milligram pills. A standard dose of tamoxifen is usually 20 milligrams a day. Tamoxifen can also be taken in lower doses (“babytam”). Below, you can read more about babytam.

A liquid form of tamoxifen (Soltamox) is available for people who have trouble swallowing pills.

It’s important to take tamoxifen around the same time every day.

Low-dose tamoxifen, or babytam

Low-dose tamoxifen, sometimes called babytam by doctors, can be used in certain situations to help reduce the side effects of this medicine. A study called TAM-01 found that 5 milligrams of daily tamoxifen lowers the risk of cancer in women who have breast cell changes associated with higher risk.

This trial did not compare the 5-milligram dose to the standard 20 milligrams and did not include people with invasive breast cancer. However, after following the women for 10 years, the study provided reassurance that babytam is an option for women who can’t tolerate the higher dose and are taking tamoxifen for the following reasons:

• To reduce the risk of invasive breast cancer if they’ve been diagnosed with ductal carcinoma in situ (DCIS), which is stage 0 noninvasive breast cancer.
• To reduce the risk of developing a first-time breast cancer if they’ve been diagnosed with lesions that are benign (not cancer) but increase future risk of breast cancer, such as:
  • Atypical ductal hyperplasia (ADH), which is abnormal cell growth in a breast duct
  • Lobular carcinoma in situ (LCIS), which is abnormal cell growth in a breast lobule

How long is tamoxifen or other hormonal therapy given?

In early-stage breast cancer, the type of hormonal therapy recommended, and how long you take it, depends on several factors:

• Whether you’re premenopausal or postmenopausal
• The risk of recurrence, based on the cancer’s features and test results
• How well you tolerate hormonal therapy
• Whether a longer duration of treatment may have more benefit for you

Certain tests may be done on the cancer to help you and your healthcare team make decisions about how long to take hormonal therapy (5 versus 10 years). Examples include EndoPredict and the Breast Cancer Index test. You can learn more about these tests on the Genomic testing in early-stage breast cancer page.

These are some examples of possible treatment durations:

• An aromatase inhibitor for 5-10 years
• Tamoxifen for 5-10 years
• Tamoxifen for 2-3 years, followed by an aromatase inhibitor for up to 5 more years
• Tamoxifen for 5 years, plus 5 years of an aromatase inhibitor
• Tamoxifen or an aromatase inhibitor, plus medicine that slows ovarian function (GnRH agonist), for 5 years

If you’re taking a GnRH agonist as well, that’s usually given for the first 2-5 years.

In metastatic breast cancer, tamoxifen, or another type of hormonal therapy, may be taken as long as it is working to treat the cancer.

If tamoxifen is taken for breast cancer prevention, it’s typically recommended for 5 years.

For men with breast cancer, tamoxifen may be taken for 5-10 years.

Learn more about treatment for hormone receptor-positive metastatic breast cancer.

Side effects

Like any medicine, tamoxifen can cause side effects. The experience is different for each person. For some people, they may be manageable, while others may find them very difficult. It’s important to talk with your doctor about what to expect and ways to prevent or manage side effects.

Common side effects include:

• Fatigue
• Menopausal symptoms such as hot flashes, joint stiffness and vaginal dryness
• Nausea
• Hair thinning
• Loss of interest in sex
• Loss of sexual ability (in men)
• Difficulty with memory and concentration, especially with long-term use

Taking tamoxifen also has helpful side effects that are not related to cancer. These include:

• Preventing bone loss in postmenopausal women
• Lowering total cholesterol levels

Rare side effects

Blood clots are a rare but serious side effect of tamoxifen. They usually occur in the leg, but clots can travel from the legs to the lungs.

• Signs of a blood clot in the leg can include pain, warmth, and/or swelling of the leg.
• Signs of a blood clot in the lungs can include shortness of breath, chest pain, or fever.

If you experience any of these, it is important to seek emergency medical attention. Blood clots can also cause a stroke.

Some people have a higher risk of blood clots due to a family history of clots, smoking, older age, an inactive lifestyle, and/or other medical problems. Talk to you doctor about your medical history and possible risk factors.

Increased risk of endometrial cancer, a cancer in the lining of the uterus, is another rare but serious side effect of tamoxifen. If you are experiencing abnormal vaginal bleeding, let your doctor know.

Additional rare side effects of tamoxifen include:

• Mood changes
• Bone loss in premenopausal women
• Cataracts, or problems with vision
• Liver problems
• Depression

Talk to your healthcare team if you're concerned about your risk for any of these side effects.

How well does tamoxifen work for breast cancer?

In women diagnosed with early-stage breast cancer or who have a high risk of developing breast cancer, tamoxifen has been shown to:

• Reduce the risk of recurrence up to 50% in the first 5 years of treatment and up to 30% in the next 5 years
• Reduce the risk of developing invasive breast cancer by about 50% in postmenopausal women who are at high risk
• Reduce the risk of developing breast cancer for at least 20 years after 5 years of treatment

Taking other medicines with tamoxifen

Some medicines may affect how well tamoxifen works. For example, CYP2D6 inhibitors are medicines that prevent a liver enzyme called CYP2D6 from converting tamoxifen into its active form. This type of medicine may stop tamoxifen from working as well as it could.

CYP2D6 inhibitors include some antidepressants. If an antidepressant is needed, your healthcare provider may recommend a moderate CYPD26 inhibitor instead of a strong one.

Here are common CYPD26 inhibitors and what they’re used to treat:

Selective serotonin reuptake inhibitors (SSRIs): strong CYPD26 inhibitors

• Fluoxetine (Prozac): depression and anxiety
• Fluvoxamine (Luvox): depression
• Paroxetine (Paxil): depression and anxiety

Selective serotonin reuptake inhibitors (SSRIs): moderate CYPD26 inhibitors

• Sertraline (Zoloft): depression and anxiety
• Citalopram (Celexa): depression
• Escitalopram (Lexapro, Cipralox): depression

Serotonin-norepinephrine reuptake inhibitors (SNRIs): moderate CYPD26 inhibitors

• Duloxetine (Cymbalta): depression and anxiety
• Venlafaxine (Effexor): depression

Norepinephrine-dopamine reuptake inhibitors (NDRIs)

• Bupropion (Wellbutrin): depression

Tricyclic antidepressants

• Clomipramine (Anafranil): depression
• Desipramine (Norpramin): depression
• Imipramine (Tofranil): depression

CYPD26 inhibitors for other mental health conditions

CYPD26 inhibitors for other mental health conditions can also interfere with tamoxifen.

These can include certain medicines for attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, and schizophrenia:

Medicines for ADHD

• Methylphenidate (Ritalin/Concerta)
• Some antidepressants are used off-label to ease symptoms of ADHD. Off-label means a drug is used in a way that is not approved by the FDA, but its use in a certain situation is legal because:
  • Its use is based on strong scientific evidence
  • Your doctor carefully considers how it may help you and what the risks are

Medicines for bipolar disorder

• Chlorpromazine (Thorazine)
• Haloperidol (Haldol)

Medicines for schizophrenia

• Chlorpromazine (Thorazine)
• Clozapine (Clozaril)
• Haloperidol (Haldol)

Other medicines that inhibit CYP2D6

Other CYP2D6 inhibitors that can interfere with tamoxifen include:

• Cinacalcet (Sensipar), which is used to treat hyperparathyroidism (over-production of a hormone called parathyroid) in people with kidney disease
• Quinidine, which is used to treat irregular heart rhythms
• Diphenhydramine (Benadryl), which is used to treat allergies
• Cimetidine (Tagamet), which is used to treat stomach ulcers and heartburn

If tamoxifen has been recommended for you, tell your doctor about all medicines and supplements you take. If you need to take a medicine that inhibits CYP2D6, discuss the risks with your care team. There may be other hormonal therapy options for you.