Tamoxifen (Nolvadex, Soltamox)

How Tamoxifen Works

About 2 out of 3 breast cancers have estrogen receptors (ER-positive) and often progesterone receptors (PR-positive). These receptors are like locks on the cancer cell. When estrogen (the key) fits into the lock, it signals the cell to grow.

Tamoxifen fits into the estrogen receptor and blocks it, so estrogen cannot switch on growth. It does not lower the amount of estrogen in your blood. In fact, in women who still have periods, estrogen levels can rise on tamoxifen. That is the key difference from aromatase inhibitors such as letrozole, which lower estrogen production.

Why it is called a "modulator"

Tamoxifen does not act the same way everywhere in the body. It is a selective estrogen receptor modulator:

• In breast tissue, it blocks estrogen. This is how it treats and prevents breast cancer.
• In the lining of the uterus, it acts partly like estrogen. This explains the higher risk of endometrial changes and uterine cancer.
• In bone after menopause, it acts like estrogen and helps keep bones strong. (Before menopause, it can cause a small amount of bone loss.)
• In the liver, it acts like estrogen, which lowers LDL cholesterol but also raises clotting factors, increasing the risk of blood clots.

Tamoxifen is a "prodrug"

Your liver converts tamoxifen into more active forms, mainly endoxifen, using an enzyme called CYP2D6. Some antidepressants and other medicines block this enzyme and may lower endoxifen levels. This is why your care team reviews your other medicines (see Drug Interactions).

FDA-Approved Uses

Tamoxifen is approved by the U.S. Food and Drug Administration (FDA) for these uses:

Other common uses

• Premenopausal women with early breast cancer: Tamoxifen alone, or tamoxifen with ovarian suppression for higher-risk cancers, is a standard option in ASCO and NCCN guidelines.
• Men with breast cancer: ASCO guidelines recommend tamoxifen as the standard hormone therapy for men with hormone receptor-positive early breast cancer. Aromatase inhibitors alone do not lower estrogen enough in men.
• After aromatase inhibitor side effects: Postmenopausal women who cannot tolerate letrozole, anastrozole or exemestane often switch to tamoxifen to finish their planned treatment.
• Low-dose tamoxifen: A 5 mg daily dose has been studied for women with atypical hyperplasia, lobular carcinoma in situ, or low-risk DCIS. This is not the FDA-labeled dose; discuss it with a specialist.

How much does it help?

Large pooled analyses by the Early Breast Cancer Trialists' Collaborative Group show that about 5 years of tamoxifen for ER-positive early breast cancer lowers the risk of recurrence by roughly a third to a half over 15 years and lowers breast cancer deaths by about a third. In the ATLAS trial, continuing to 10 years lowered the risk further, especially after year 10. In the NSABP P-1 prevention trial, tamoxifen lowered the risk of invasive breast cancer by about half in high-risk women. Your own benefit depends on your cancer and your risk, so ask your oncologist for numbers that apply to you.

Dosing and How to Take It

• Take it once a day at about the same time. With or without food is fine.
• Swallow tablets with water. If you have trouble swallowing pills, ask about the oral liquid (Soltamox).
• Missed dose: Take it when you remember that day. If it is almost time for the next one, skip the missed dose. Do not take two doses at once. Because tamoxifen stays in the body for a long time, an occasional missed dose is unlikely to matter, but regular missed doses do.
• No routine dose changes are needed for older age or kidney problems.
• Sequencing: Some postmenopausal women take tamoxifen for 2 to 3 years, then switch to an aromatase inhibitor to complete 5 years or more. Others take an aromatase inhibitor after 5 years of tamoxifen (extended therapy).

Side Effects

Most people can take tamoxifen without serious problems. Many side effects are caused by blocking estrogen and are similar to menopause symptoms.

Common side effects

• Hot flashes and night sweats: The most common side effect. In the P-1 prevention trial, about 80% of women on tamoxifen reported hot flashes, compared with about 68% on placebo. They are often worst in the first months and may ease over time.
• Vaginal discharge or dryness: A clear or white discharge is common. Dryness, itching, or pain with sex may also occur.
• Changes to periods: Periods may become irregular, lighter, or stop. This does not mean you cannot get pregnant (see Pregnancy).
• Mood changes: Some people notice low mood, irritability, or anxiety.
• Fatigue and sleep problems, often linked to night sweats.
• Leg cramps, mild nausea, fluid retention, and lower sex drive.
• Hair thinning: Usually mild.

Less common but serious side effects

• Blood clots in the legs (deep vein thrombosis) or lungs (pulmonary embolism)
• Stroke
• Endometrial cancer and uterine sarcoma (cancer of the uterus)
• Endometrial changes such as polyps or thickening of the lining
• Cataracts and, rarely, other eye changes
• Liver changes: fatty liver is fairly common; serious liver injury is rare
• High calcium and "flare": people with cancer in the bones may have a short-term increase in bone pain or blood calcium in the first weeks
• Low blood counts: uncommon

Possible benefits beyond cancer

• After menopause, tamoxifen helps preserve bone density.
• It tends to lower LDL ("bad") cholesterol.

Serious Risks Explained

The boxed warning can sound frightening. It helps to look at the actual size of the risks. The numbers below come from the NSABP P-1 trial in high-risk women without cancer, which is described in the FDA label. Rates are per 1,000 women per year.

In absolute terms, most women taking tamoxifen will not have any of these events. Risk is higher with age over 50, previous blood clots, recent surgery, long periods without moving, smoking, and obesity.

Who should not take tamoxifen

• Anyone allergic to tamoxifen
• For risk reduction or DCIS: women who have had a blood clot in a leg or the lungs, or who need a blood thinner such as warfarin
• Anyone who is pregnant

For people with invasive breast cancer, a past clot is not always a reason to avoid tamoxifen, but an aromatase inhibitor is often preferred after menopause. Your oncologist will weigh this with you.

Lowering your risk

• Report any vaginal bleeding after menopause or any unusual bleeding, spotting, or pelvic pain promptly.
• Before planned surgery, tell the surgeon you take tamoxifen. Some teams pause it for a short time around major surgery to lower clot risk. Do not stop without talking to your oncologist.
• On long trips, walk around and stretch your legs regularly and stay hydrated.
• Do not smoke, and keep blood pressure and diabetes under control.

Drug Interactions

Always tell your oncologist and pharmacist about every medicine, supplement, and herbal product you take.

Medicines that may weaken tamoxifen (CYP2D6 inhibitors)

Strong CYP2D6 blockers can lower levels of endoxifen, the active form of tamoxifen. Whether this changes cancer outcomes is still debated, but guidelines advise choosing alternatives when possible.

• Avoid if possible: paroxetine (Paxil), fluoxetine (Prozac), bupropion (Wellbutrin, Zyban), quinidine, and terbinafine taken for long periods
• Usually preferred instead: venlafaxine (Effexor), desvenlafaxine, and in many cases citalopram or escitalopram, which have little or weaker effect on CYP2D6
• This matters most for people who take antidepressants or need a medicine for hot flashes.

Blood thinners

• Warfarin (Coumadin): Tamoxifen can greatly increase warfarin's effect and the risk of bleeding. If both are needed for cancer treatment, INR needs close monitoring. Warfarin use is a reason not to take tamoxifen for risk reduction or DCIS.

Other interactions

• Aromatase inhibitors (letrozole, anastrozole): Taking them at the same time as tamoxifen is not recommended. Tamoxifen lowers their blood levels, and combining them gave no extra benefit in the ATAC trial. Taking them one after the other is standard.
• Rifampin and other strong enzyme inducers can lower tamoxifen levels.
• Estrogen and hormonal birth control: Not used during tamoxifen treatment for breast cancer, because they may counteract it and some contain hormones that can feed the cancer.
• Other medicines that raise clot risk may add to tamoxifen's risk; discuss them with your team.

Food and supplements

• No special diet is needed. Soy foods in normal amounts are considered safe; concentrated soy or isoflavone supplements are usually avoided.
• Herbal products marketed for menopause can contain plant estrogens. Check with your pharmacist first.

Monitoring

• Gynecologic care: Keep up with regular gynecologic exams. Routine ultrasound or biopsy of the uterus is not recommended for women without symptoms, but any abnormal bleeding should be checked promptly (ACOG guidance).
• Eye exams: Have your eyes checked if you notice any change in vision. Some doctors recommend a baseline eye exam.
• Blood tests: The FDA label advises periodic blood counts and liver tests.
• Calcium: People with cancer in the bones may need calcium levels checked when starting.
• Breast imaging: Continue mammograms as recommended for survivors or for high-risk screening.
• Bone density: Premenopausal women may lose a small amount of bone on tamoxifen; ask whether a bone density scan is right for you.
• Side effect check-ins: Every visit is a chance to discuss hot flashes, mood, sexual health and whether you are able to take every dose.

Pregnancy, Fertility and Periods

• Do not get pregnant while taking tamoxifen. It can harm a developing baby. Use effective non-hormonal birth control (such as a copper IUD or condoms) during treatment and for 2 months after the last dose.
• Tamoxifen can make you more fertile, not less. In premenopausal women it can stimulate the ovaries, so pregnancy is possible even if periods are irregular or stop.
• Planning a pregnancy? The POSITIVE trial studied a planned pause in hormone therapy after at least 18 months of treatment to try for pregnancy, with no clear short-term increase in recurrence. Talk with your oncologist before making any change.
• Breastfeeding: Not recommended during treatment and for 3 months after the last dose (per the FDA label).

Tamoxifen vs. Aromatase Inhibitors

For postmenopausal women, aromatase inhibitors such as letrozole, anastrozole and exemestane lower the risk of recurrence somewhat more than tamoxifen. Tamoxifen remains the main choice before menopause (unless the ovaries are suppressed) and for men.

Many people take both, one after the other. Read more in our hormone therapy overview.

Cost and Financial Help

• Generic tamoxifen tablets are among the least expensive cancer medicines. With insurance or a pharmacy discount card, a month's supply often costs less than $30 in the U.S.; prices vary.
• Soltamox (liquid) costs much more. Insurers may require a reason, such as trouble swallowing.
• Medicare Part D and most commercial plans cover generic tamoxifen. Mail-order 90-day supplies can lower cost.
• If cost is a problem, ask your oncology social worker or pharmacist about patient assistance programs, nonprofit copay foundations, and lower-cost pharmacies. Do not skip doses to save money.

Frequently Asked Questions