Tamoxifen

Tamoxifen is a hormonal therapy drug used in the treatment or risk reduction of hormone receptor-positive breast cancer. Tamoxifen can be used:

• To reduce the risk of hormone receptor-positive early-stage breast cancer coming back
• To treat hormone receptor-positive metastatic breast cancer
• To lower the risk of breast cancer in people who’ve never been diagnosed but who have a high risk for developing it

Tamoxifen is part of a class of drugs known as SERMs, or selective estrogen receptor modulators. SERMs are sometimes called estrogen blockers because they block estrogen from attaching to estrogen receptors on breast cancer cells. When tamoxifen blocks the receptors, estrogen is no longer able to attach and signal the cancer cells to grow.

How does tamoxifen work?

Tamoxifen works by blocking estrogen from binding to estrogen receptors in hormone receptor-positive breast cancer cells. Without the estrogen, the cancer cells can’t grow as well as they can with it.

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

When is tamoxifen prescribed?

Tamoxifen may be prescribed to treat hormone receptor-positive breast cancer:

• After surgery (adjuvant treatment) for early-stage breast cancer
• 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

How is tamoxifen given?

Tamoxifen is taken daily as a pill (Nolvadex) and should be swallowed whole. A standard dose of tamoxifen is usually 20 milligrams a day. A liquid form of tamoxifen (Soltamox) is also available for people who have trouble swallowing. It’s important to take tamoxifen around the same time every day.

Most men who take tamoxifen to treat breast cancer take it alone. For women, risk of recurrence can play a role in whether tamoxifen is taken alone or with medicine that suppresses ovarian function.

Choice of hormonal therapy in early-stage breast cancer

Tamoxifen is approved for women of any menopausal status (premenopausal, perimenopausal, or postmenopausal). Pre- and perimenopausal women may be offered tamoxifen alone, tamoxifen in combination with medicine to suppress ovarian function, or a different type of hormonal therapy called an aromatase inhibitor in combination with ovarian function suppression medicine.

Medicines that suppress ovarian function are called gonadotropin-releasing hormone (GnRH) agonists (sometimes also called luteinizing hormone-releasing hormone agonists, or LHRH agonists). These drugs send a message to the brain that in turn stops the ovaries from producing estrogen, putting a premenopausal woman into menopause for as long as she is receiving the drug. Ovarian function can also be suppressed through oophorectomy, or surgical removal of the ovaries, which causes permanent menopause.

Research has shown that in premenopausal women with early-stage breast cancer, adding ovarian function suppression medicine to tamoxifen or to aromatase inhibitor treatment improves disease-free survival. However, adding this medicine to hormonal therapy can also increase side effects, so it’s important to talk with your healthcare team about what’s right for you.

Whatever your menopausal status, the choice of which therapy to use is based on risk of recurrence and whether you have been diagnosed with early-stage or metastatic breast cancer.

It’s important to know that it is not safe to get pregnant while taking tamoxifen, because tamoxifen can harm an unborn baby. But results from the POSITIVE trial show that most premenopausal women diagnosed with early-stage hormone receptor-positive breast cancer who want to have a baby can safely pause hormonal therapy temporarily to get pregnant without increasing the risk of breast cancer recurrence. 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 pause hormonal therapy. It’s important to make decisions with your care team about which treatment plan is best for you.

How long tamoxifen or other hormonal therapy is given

No matter what kind of hormonal therapy is recommended, in early-stage breast cancer, the type and duration of hormonal therapy is individualized based on tolerance of treatment, the risk of recurrence, and whether there may be a potential benefit to continue. Additional tests may be performed on the cancer that can help you and your healthcare team make decisions about the duration of hormonal therapy (five versus 10 years). Here are some examples of different treatment durations:

• Some people may take tamoxifen for five years, followed by an additional five years of tamoxifen or an aromatase inhibitor.
• Other people may take tamoxifen or an aromatase inhibitor plus ovarian function suppression medicine for five years and then stop.
• Some people may switch to an aromatase inhibitor after two or three years of tamoxifen, for a total of five or more years of hormonal therapy.

In metastatic breast cancer, tamoxifen may be taken as long as it is working to treat the cancer. Learn more about treatment for hormone receptor-positive metastatic breast cancer.

Low-dose tamoxifen, or babytam

Low-dose tamoxifen, sometimes called babytam by doctors, is also used in certain situations and can help reduce the side effects of tamoxifen. A recent study of low-dose tamoxifen used a five-milligram dose. This trial did not compare the five-milligram dose to the standard 20 milligrams and did not include people with invasive breast cancer. However, it did provide some assurance that babytam may be used as a treatment option for women who are having difficulty tolerating the standard dosing and are taking tamoxifen for the following reasons:

• To reduce the risk of breast cancer recurrence in people who’ve been diagnosed with ductal carcinoma in situ (DCIS), which is stage 0 noninvasive breast cancer.
• As preventative therapy to reduce the risk of developing breast cancer in people diagnosed with lesions that are benign but increase the future risk for developing 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

Side effects

As with any medicine, taking tamoxifen can cause side effects. Each person taking tamoxifen has their own unique experience of side effects. For some people, they may be manageable. For other people, they can be very difficult. It’s important to talk with your doctor about what to expect and ways to prevent or manage side effects. Common tamoxifen side effects include:

• Fatigue
• Menopausal symptoms such as hot flashes 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 blood clots can spread 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.

People who have a high risk of blood clots are those with a family history of blood clots, who are smokers, who are older, and those who have an inactive lifestyle and other medical problems.

Additional rare side effects of tamoxifen include:

• Mood changes
• Bone loss in premenopausal women
• Endometrial cancer or uterine sarcoma, a rare uterine cancer
• Cataracts, or problems with vision
• Liver problems
• Depression

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 five years of treatment and up to 30% in the next five 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 five 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. These kinds of drugs may stop tamoxifen from working as well as it could.

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

Selective serotonin reuptake inhibitors (SSRIs)

• Citalopram (Celexa): depression
• Escitalopram (Lexapro/Cipralox): depression
• Fluoxetine (Prozac): depression and anxiety
• Fluvoxamine (Luvox): depression
• Paroxetine (Paxil): depression and anxiety
• Sertraline (Zoloft): depression and anxiety

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

• 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 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.