What are the risks of taking Tamoxifen (tamoxifen citrate)?

From the Guidelines

Tamoxifen carries significant risks, including an increased chance of developing endometrial cancer, blood clots, and stroke, which must be carefully weighed against its benefits in reducing breast cancer recurrence. The most serious risks associated with tamoxifen include:

• An increased chance of developing endometrial cancer (cancer of the uterine lining) in women with a uterus, with a risk ratio of 4.01 (95% CI, 1.70–10.90) in women aged 50 years or older 1
• Blood clots such as deep vein thrombosis or pulmonary embolism, with a risk ratio of 1.71 (95% CI, 0.85–3.58) in women aged 50 years or older 1
• Stroke, with a risk ratio of 1.75 (95% CI, 0.98–3.20) in women aged 50 years or older 1 Other significant side effects include:
• Hot flashes
• Vaginal discharge
• Irregular menstrual periods
• Mood changes
• Visual disturbances
• Cataracts, with a risk ratio of 1.14 (95% CI, 1.01–1.29) 1
• Liver problems
• Bone pain and joint pain, particularly when first starting the medication
• Changes in blood lipid levels
• Increased risk of fatty liver disease These risks must be balanced against the benefits of tamoxifen, which is highly effective at reducing breast cancer recurrence in hormone-receptor positive breast cancer patients, with a relative risk of 0.73 (95% CI, 0.58–0.91; P = .004) 1. Regular monitoring with your healthcare provider, including gynecological exams for women with a uterus, is essential while taking tamoxifen, which is typically prescribed for 5-10 years depending on your specific situation.

From the FDA Drug Label

In the studies described under "What are the benefits of tamoxifen citrate tablets? ", the high-risk women who took tamoxifen citrate tablets got certain side effects at a higher rate than those who took a placebo. Some of these side effects can cause death In one study, in women who still had their uterus: Out of every 1,000 women who took a placebo, each year 1 got endometrial cancer (cancer of the lining of the uterus) and none got uterine sarcoma (cancer of the body of the uterus). Out of every 1,000 women who took tamoxifen citrate tablets, each year 2 got endometrial cancer and fewer than 1 got uterine sarcoma These results show that, on average, in high-risk women who still had their uterus, tamoxifen citrate tablets doubled the chance of getting endometrial cancer from 1 in 1,000 to 2 in 1,000, and it increased the chance of getting uterine sarcoma The risk is different for women who no longer have their uterus For all women in this study, taking tamoxifen citrate tablets increased the risk of having a blood clot in their lungs or veins, or of having a stroke. In some cases, women died from these effects. Tamoxifen citrate tablets increased the risk of getting cataracts (clouding of the lens of the eye) or needing cataract surgery.

The risks of taking tamoxifen citrate tablets include:

• Endometrial cancer: The chance of getting endometrial cancer is doubled, from 1 in 1,000 to 2 in 1,000 per year.
• Uterine sarcoma: The chance of getting uterine sarcoma is increased.
• Blood clots: The risk of having a blood clot in the lungs or veins is increased.
• Stroke: The risk of having a stroke is increased.
• Cataracts: The risk of getting cataracts or needing cataract surgery is increased. These risks can be serious and potentially life-threatening 2.

From the Research

Risks of Taking Tamoxifen

The risks associated with taking tamoxifen include:

• Increased risk of endometrial cancer, with a relative risk of 2 to 4 times higher than for postmenopausal women not taking tamoxifen 3
• Increased risk of thromboembolic events, such as blood clots 3
• Ocular toxicity and hepatotoxicity, although these are rare 3
• Vasomotor symptoms, such as hot flashes and night sweats, which are the most commonly reported side effects 3
• Vaginal discharge or dryness, nausea, and depression, which are less frequently reported 3

Endometrial Cancer Risk

The risk of endometrial cancer increases with the duration of tamoxifen use:

• Women who take tamoxifen for more than 5 years have a 4.06-fold greater odds of developing endometrial cancer than non-users 4
• The risk of endometrial cancer associated with tamoxifen use is stronger among heavier women and those with a history of estrogen replacement therapy (ERT) 4
• The risk of endometrial cancer does not diminish in follow-up to at least 5 years after the last treatment ended 5

Mortality Risk

The mortality risk from endometrial cancer is increased in women who take tamoxifen for at least 5 years:

• Tamoxifen use for at least 5 years is associated with increased endometrial cancer mortality, with a hazard ratio of 1.59 (1.13 to 2.25) 6
• The increased mortality risk is due primarily to the excess of unfavorable histologies and advanced stage in women using tamoxifen for 5 or more years 6

Prognosis

The prognosis of endometrial cancer is worse in women who take tamoxifen long-term:

• Long-term tamoxifen users have a worse prognosis of endometrial cancers, with a 3-year endometrial-cancer-specific survival of 76% for those who used tamoxifen for at least 5 years, compared to 94% for non-users 7
• The worse prognosis is due to less favorable histology and higher stage in long-term tamoxifen users 7