Tamoxifen

Tamoxifen, the generic name of Nolvadex, is the oldest and most-prescribed SERM. Tamoxifen is approved by the U.S. Food and Drug Administration (FDA) to treat:

• women diagnosed with hormone-receptor-positive, early-stage breast cancer after surgery (or possibly chemotherapy and radiation) to reduce the risk of hormone-receptor-positive breast cancer coming back (recurring)
• women and men diagnosed with advanced (metastatic) hormone-receptor-positive disease to produce regression and remission of the disease

Tamoxifen also is used to:

• reduce breast cancer risk in women who haven't been diagnosed but are at higher-than-average risk for disease

Tamoxifen won't work on hormone-receptor-negative breast cancer.

Tamoxifen is a pill taken once a day. Most doctors recommend taking tamoxifen at the same time each day.

Benefits of tamoxifen

Cell with estrogen receptors blocked by tamoxifen and helper proteins.

• Larger Version

Since its approval in 1998, tamoxifen has been used to treat millions of women and men diagnosed with hormone-receptor-positive breast cancer. While an aromatase inhibitor is the first hormonal therapy medicine choice for post-menopausal women, tamoxifen is the first choice for pre-menopausal women and is still a good choice for post-menopausal women who can't take an aromatase inhibitor.

Tamoxifen can:

• reduce the risk of breast cancer coming back by 40% to 50% in post-menopausal women and by 30% to 50% in pre-menopausal women
• reduce the risk of a new cancer developing in the other breast by about 50%
• shrink large, hormone-receptor-positive breast cancers before surgery
• slow or stop the growth or advanced (metastatic) hormone-receptor-positive breast cancer in both pre- and post-menopausal women
• lower breast cancer risk in women who have a higher-than-average risk of disease but have not been diagnosed

Tamoxifen offers other health benefits that aren't related to treating cancer. Because it's a SERM, it selectively either blocks or activates estrogen's action on specific cells. While tamoxifen blocks estrogen's action on breast cells, it activates estrogen's action in bone and liver cells. So tamoxifen can:

• help stop bone loss after menopause
• lower cholesterol levels

Some people may not get the full benefit of tamoxifen

The body uses an enzyme called CYP2D6 to convert tamoxifen into its active form. Two things can interfere with the body’s ability to make this happen: a flaw in the CYP2D6 enzyme and certain medications that block the effectiveness of this enzyme.

• Abnormal CYP2D6 enzyme: About 10% of people have a CYP2D6 enzyme that doesn’t function as well as it should. Having an abnormal CYP2D6 enzyme might keep a person from getting the full benefit of tamoxifen. Ask your doctor about being tested for this enzyme abnormality if you are seriously considering taking tamoxifen.
• Medications that can interfere with CYP2D6: There are medications that can block the activity of CYP2D6 to varying degrees (usually stated as “strong” or “moderate” inhibitors of CYP2D6). These medications include some of the antidepressants known as serotonin-specific reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). There are also other types of commonly prescribed medications, such as Cardioquin (chemical name: quinidine), Benadryl (chemical name: diphenhydramine), and Tagamet (chemical name: cimetidine), that can block CYP2D6. Blocking the activity of CYP2D6 can interfere with the activation of tamoxifen — reducing its effectiveness as an anti-cancer treatment. Most doctors recommend that you avoid taking strong and moderate inhibitors of CYP2D6 while you’re on tamoxifen.
  
  If you have already finished tamoxifen and you were taking other medications at the same time, make an appointment to talk with your doctor about whether any of your other medications may have interfered with CYP2D6 and the potential benefit you received from tamoxifen. Your doctor may recommend no additional therapy or extended hormonal therapy (with tamoxifen or an aromatase inhibitor) depending on your risk of recurrence, your overall medical condition, and your preferences.
  
  If you were taking tamoxifen because you are at high risk but have never been diagnosed, and you were also taking a CYP2D6 inhibitor, your doctor may now recommend additional anti-estrogen therapy with tamoxifen or Evista (chemical name: raloxifene), depending on your menopausal status. Talk to your doctor about what’s best for your situation.
  
  If you had progression of breast cancer while on both tamoxifen and a strong or moderate CYP2D6 inhibitor, you can’t assume that tamoxifen failed to work. Rather, it’s possible that tamoxifen never had a fair chance at getting the cancer under control because its action was blocked by the other medicine. Moving forward, tamoxifen, without a CYP2D6 inhibitor, may still provide significant benefit.

For those taking raloxifene (brand name: Evista)

The CYP2D6 enzyme is not needed to activate raloxifene (brand name: Evista, a sister medicine to tamoxifen, used to reduce the risk of developing hormone-receptor-positive breast cancer and treat osteoporosis in postmenopausal women).

Medicines to avoid while taking tamoxifen

In the list below, the medications under the headings “Strong Inhibitors” and “Moderate Inhibitors” can inhibit CYP2D6 and interfere with the effectiveness of tamoxifen. The medications under the heading “Not Inhibitors” do not block the CYP2D6 enzyme and will not interfere with tamoxifen treatment.

This list is incomplete and subject to change over time. Use it as a starting place and ask your doctor if any medications you are taking or that are recommended to you are compatible with tamoxifen.

Source: Flockhart DA. ©2008. Consortium on Breast Cancer Pharmacogenomics. Indiana University School of Medicine.

Side effects of tamoxifen

Tamoxifen's selective estrogen activation effects can cause some serious side effects, including blood clots, stroke, and endometrial cancer. If you and your doctor are considering tamoxifen as part of your treatment plan, tell your doctor if you smoke or have a history of blood clots or heart attack. If you're taking tamoxifen, call your doctor immediately if you have any of these symptoms:

• abnormal vaginal bleeding or discharge
• pain or pressure in the pelvis
• leg swelling or tenderness
• chest pain
• shortness of breath
• weakness, tingling, or numbness in your face, arm, or leg
• difficulty speaking or understanding
• sudden difficulty seeing
• dizziness
• sudden severe headache

The most common side effects of tamoxifen are:

• increased tumor or bone pain
• hot flashes
• nausea
• fatigue
• mood swings
• depression
• headache
• hair thinning
• constipation
• dry skin
• loss of libido

Hot flashes or night sweats from taking tamoxifen can be troubling. But a 2008 British study suggests that women who experienced hot flashes and night sweats while taking hormonal therapy medicine were less likely to have the breast cancer come back (recur). Knowing that this side effect might indicate a reduced risk of the cancer coming back may help some people stick with treatment despite the side effects.

Some women on tamoxifen have reported memory problems while taking the medicine. While no definitive results are available yet, the ongoing Co-STAR (Cognition in the Study of Tamoxifen and Raloxifene) trial is looking at the effects tamoxifen and Evista (chemical name: raloxifene), another SERM, have on memory and thinking.

How long do I take tamoxifen?

Some women may take tamoxifen for 5 years. Other women may take it for 2 or 3 years and then switch to an aromatase inhibitor. Depending on your unique situation, your doctor may recommend that you take tamoxifen for a longer or shorter amount of time.

Does insurance cover tamoxifen?

While costs vary, tamoxifen is usually less expensive than an aromatase inhibitor because it is a generic medicine. If you have health insurance, check with your insurance company to see if and how much of the cost of tamoxifen is covered. If you don't have health insurance or your insurance doesn't cover the cost of tamoxifen, ask your doctor or nurse about programs in your area that may be able to help.