Coping With the Side
Effects of Tamoxifen
The drug tamoxifen is approved by the U.S. Food and Drug Administration (FDA) to help treat early and advanced stages of breast cancer and prevent breast cancer recurrence (return). Tamoxifen is also FDA approved to help prevent breast cancer in women at high risk of the disease. Tamoxifen is an "anti-estrogen" and works by competing with estrogen to bind to estrogen receptors in breast cancer cells. By blocking the actions of estrogen in the breast tissue, tamoxifen helps slow the growth and reproduction of breast cancer cells.
While taking tamoxifen may benefit many breast cancer patients (and women at high risk of the disease), tamoxifen has also been shown to cause bothersome side effects in some women. In some instances, serious complications including deep vein thrombosis, endometrial cancer, and stroke may develop from tamoxifen use. Women should carefully discuss their specific risk factors for cardiovascular and other diseases with their physicians and assess the benefits and risks of taking tamoxifen for the treatment or prevention of breast cancer before beginning treatment.
This section discusses the possible side effects and complications from tamoxifen, and includes information on how women may cope with a number of these side effects.
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Possible Side Effects of Tamoxifen
Though the overall occurrence of side effects is relatively low among women who take tamoxifen, the following side effects have been reported. Many women only experience one or two of these side effects and some women do not experience any. Women who are considering tamoxifen should discuss all potential benefits and risks with their physicians prior to treatment. In many cases, the benefit of treating or preventing breast cancer with tamoxifen outweighs the risk of these side effects.
Hot flashes and other menopausal symptoms: The most commonly reported side effect among women who take tamoxifen is a higher occurrence of hot flashes (approximately 50% of women on tamoxifen experience hot flashes when compared with a placebo, an inactive pill). Hot flashes may be accompanied by sweating, flushing, or heart palpitations. Hot flashes occur when estrogen is blocked in the hypothalamus, the part of the brain that controls the body’s thermostat. Some women find that regular exercise can help reduce hot flashes. If the hot flashes are particularly bothersome and do not respond to conservative measures such as exercise, calcium, or other interventions, physicians may prescribe medications such as clonidine (brand name, Duraclon) or Megace (brand name, Megestrol). Physicians may also recommend taking 30 to 60-day "breaks" from tamoxifen to help reduce hot flashes and other menopausal symptoms.
It is important to note that hot flashes and other menopausal symptoms were also reported in women not taking tamoxifen (i.e., the placebo group) in the National Adjuvant Breast and Bowel Project’s (NSABP) first Breast Cancer Prevention Trial. In this trial, 80% of women on tamoxifen experienced hot flashes while 68% of women who took a placebo (inactive pill) experienced hot flashes. Therefore, these symptoms may be related to menopause itself and not tamoxifen use. It is sometimes difficult to determine to what extent tamoxifen may contribute to these symptoms, as many women with a diagnosis of breast cancer are approaching menopause or they are post-menopausal.
Other reported menopausal symptoms in addition to hot flashes include vaginal dryness, mood changes, headaches, and irregular menstrual cycles. Women who experience vaginal dryness, irritation, or discharge are encouraged to ask their physicians about using vaginal lubricants to help relieve these symptoms. In some cases, vaginal discharge can be an indication of a more serious condition, such as endometrial cancer, and may require further investigation. Vaginal discharge was reported in 55% of women on tamoxifen in the NSABP’s Breast Cancer Prevention Trial and in 35% of women who took a placebo (inactive pill).
Tamoxifen, by itself, does not cause permanent premature menopause in younger women (i.e., women in their thirties). For most young women who take tamoxifen, the ovaries continue to act normally and produce estrogen in the same or slightly increased amounts. In fact, some studies have suggested that tamoxifen may make pre-menopausal women more fertile. Therefore, precautions to avoid pregnancy should be taken if using tamoxifen when sexually active. Tamoxifen should not be taken during pregnancy.
Nausea or vomiting: Some women who take tamoxifen may experience nausea or vomiting while on the medication. Nausea and vomiting usually cease after the first few weeks on tamoxifen. Women who experience severe nausea and vomiting while taking tamoxifen should talk to their physicians about ways to relieve these symptoms.
Depression or mood changes: A small number of women who take tamoxifen experience sharp mood swings or become severely depressed. Since depression can come on slowly, over a period of several months, some women do not realize that they are depressed. It also may be difficult to determine whether tamoxifen is the source of the patient’s depression or if other stress factors (such as coping with breast cancer and/or going through natural menopause) have contributed to the depression. Depending on the individual situation, depression may be treated with counseling or other medications. Some physicians will recommend taking 30 to 60-day "breaks" from tamoxifen to help relieve depression.
Weight gain: Large studies conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) revealed that women who took a placebo (inactive pill) were just as likely to gain weight as women who took tamoxifen. It is difficult to determine whether weight gain is caused by tamoxifen or by other factors, such as prior cancer treatment (especially certain chemotherapy regimens), changes in physical activity, changes in eating habits due to the stress of coping with breast cancer, etc. A few women who take tamoxifen experience weight loss.
Possible Serious Complications From Tamoxifen
A woman’s decision whether or not to take tamoxifen to help treat breast cancer (or prevent breast cancer) should be made carefully, weighing the benefits and risks to the medication. While the benefits of tamoxifen outweigh the risks for many breast cancer patients, serious complications have been reported in a small percentage of women on tamoxifen. These complications were noted more frequently, and sometimes exclusively, in women over the age of 50. Complications that may occur from the use of tamoxifen include the following:
Endometrial cancer (cancer of the lining of the uterus): Post-menopausal women who take tamoxifen and who have not had a hysterectomy (uterus removal) are at a higher risk of developing endometrial cancer than women who are not on tamoxifen. In the NSABP’s Breast Cancer Prevention Trial, endometrial cancer occurred 2.5 times more frequently in women who took tamoxifen compared to women who took a placebo (inactive pill).
However, the risk of endometrial cancer is still low among women on tamoxifen: approximately 2 out of 1000 women on tamoxifen will develop endometrial cancer.
A
study reported in the
Because of these findings, women on tamoxifen are encouraged to have yearly gynecological exams. Any abnormal bleeding or uterine pain should be reported to a physician immediately. Women considering tamoxifen are encouraged to have an endometrial sampling (removal of cells in the lining of the uterus for microscopic examination) to make sure there are no pre-existing uterine problems. Researchers are investigating whether women on tamoxifen should receive annual vaginal ultrasound exams to screen for endometrial thickening. However, early studies do not indicate a need for routine ultrasounds and/or endometrial biopsies unless there are specific symptoms such as vaginal bleeding or spotting.
Blood clotting (thrombosis): Women who take tamoxifen have an increased risk of blood clots compared with women who do not take tamoxifen. Blood clots will most commonly form in large veins in the legs (deep vein thrombosis). Sometimes, these blood clots can dislodge and travel to the lungs (called pulmonary embolism). Pulmonary embolism is a serious, possibly fatal condition in which a blood clot causes blockage of an artery in the lungs.
Uterine abnormalities: Some researchers have suggested that tamoxifen can increase a woman’s risk of developing uterine tumors. Tamoxifen may make endometriosis worse in women with a history of the condition. Endometriosis is a non-cancerous condition in which endometrial (lining of the uterus) tissue is found outside the uterus in other areas of the body (such as ovaries or the fallopian tubes). Tamoxifen, which can stimulate thickening and growth of the endometrial (uterine lining, can also stimulate this tissue when it is found outside the uterus, and may increase symptoms associated with endometriosis (such as pain before and during menstruation, pain during or after sexual intercourse, and heavy or irregular bleeding).
In some women, tamoxifen may stimulate the growth of uterine fibroids (bundles of tissue that grow on the wall of the uterus) or other abnormalities on the uterine wall. These conditions may make it more difficult for physicians to diagnose endometriosis.
Cataracts or other eye problems: Though rare, tamoxifen has been shown to cause cataracts (loss of clearness in the lens of the eye) or minor damage in the cornea and retina. Approximately 25 of every 1000 women on tamoxifen developed cataracts in the NSABP’s Breast Cancer Prevention Trial compared to approximately 22 of every 1000 women who took a placebo (inactive pill) Women who take tamoxifen should receive annual eye exams and report any eye problems to their physicians.
Stroke: Strokes occur more frequently among women who take tamoxifen than women who do not take tamoxifen. A stroke is a serious condition in which the supply of blood and oxygen is temporarily cut off to part of the brain. Strokes are more common in tamoxifen users who have other risk factors for stroke (such as obesity, high blood pressure, sedentary lifestyle, etc.). The risk of stroke while on tamoxifen may be related to the risk of blood clots (see the section on blood clotting above). Click here to learn more about stroke.
The following chart shows the incidence of side effects in women during the National Adjuvant Breast and Bowel Project’s (NSABP) Breast Cancer Prevention Trial (1992-1997):
|
Condition |
Incidence in women taking tamoxifen |
Incidence in women not taking tamoxifen |
|
Endometrial cancer |
2.29/1000 cases annually |
0.92/1000 cases annually |
|
Pulmonary embolism |
0.75/1000 cases annually |
0.25/1000 cases annually |
|
Deep-vein thrombosis |
1.26/1000 cases annually |
0.79/1000 cases annually |
|
Stroke |
1.43/1000 cases annually |
1.00/1000 cases annually |
|
Cataract |
25.41/1000 cases annually |
22.51/1000 cases annually |
|
Cataract surgery |
46.62/1000 cases annually |
31.43/1000 cases annually |
*source: Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen
for prevention of breast cancer: report of the National
Surgical Adjuvant Breast and Bowel Project P-1 study.
J Natl Cancer Inst. 1998;90:1371-1388.
Nolvadex
prescribing information, AstraZeneca
Pharmaceuticals LP, Wilmington,
Additional Resources and References
The medical study, "Tamoxifen
for Prevention of Breast Cancer: Report of the National Surgical Adjuvant
Breast and Bowel Project P-1 Study," is published in the