What is the risk of stroke associated with Tamoxifen (tamoxifen citrate) therapy?

From the Guidelines

Tamoxifen therapy is associated with an increased risk of stroke, particularly in postmenopausal women and those with a history of thromboembolic events.

Risk Factors and Considerations

• The risk of stroke is higher in women over 50 years old, with a risk ratio of 1.75 (95% CI, 0.98-3.20) compared to placebo 1.
• Women with a history of deep vein thrombosis, pulmonary embolus, stroke, or transient ischemic attack should not be prescribed tamoxifen due to the increased risk of thromboembolic events 1.
• The risk-benefit profile of tamoxifen is most favorable in women at greatest risk of developing breast cancer, particularly those with a 5-year projected breast cancer risk of 1.66% or higher according to the National Cancer Institute's Breast Cancer Risk Assessment Tool based on the Gail model 1.

Clinical Recommendations

• Tamoxifen (20 mg per day orally for 5 years) should be discussed as an option to reduce the risk of invasive breast cancer, specifically ER-positive breast cancer, in premenopausal or postmenopausal women at increased risk of breast cancer or with lobular carcinoma in situ (LCIS) 1.
• The benefits and risks of tamoxifen should be carefully considered during the decision-making process, taking into account the individual patient's risk factors and medical history 1.
• Regular follow-up, including a baseline gynecologic examination and annual examinations thereafter, is recommended to monitor for potential side effects and abnormal vaginal bleeding 1.

From the FDA Drug Label

There was a non-statistically significant increase in stroke among patients randomized to tamoxifen (24 placebo; 34 tamoxifen; RR = 1.42,95% CI: 0.82 to 2. 51). 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. Stroke. Stroke can cause serious medical problems, including death

The risk of stroke associated with Tamoxifen (tamoxifen citrate) therapy is increased, but not statistically significant, with a relative risk of 1.42 (95% CI: 0.82 to 2.51) 2. The exact risk is uncertain, but it is a potential side effect of tamoxifen therapy. Key points to consider are:

• Increased risk: Tamoxifen may increase the risk of stroke.
• Non-statistically significant: The increase in risk is not statistically significant, but it is still a potential concern.
• Relative risk: The relative risk of stroke is 1.42 (95% CI: 0.82 to 2.51) 2.
• Monitoring: Patients taking tamoxifen should be monitored for signs of stroke, such as sudden weakness, tingling, or numbness in the face, arm, or leg.

From the Research

Risk of Stroke Associated with Tamoxifen Therapy

• The risk of stroke associated with tamoxifen therapy is a topic of ongoing research and debate 3, 4, 5, 6, 7.
• A study published in the Journal of the National Cancer Institute in 2004 found that tamoxifen use was not associated with an increased risk of stroke, either overall or in subgroups defined by duration, dose, or recency of use 3.
• In contrast, a study published in the Journal of the National Cancer Institute in 2005 found that tamoxifen led to an increased risk of stroke, although the relative risk was not statistically significant 4.
• Another study published in Expert Opinion on Drug Safety in 2005 noted that several studies had shown an increased risk of venous thrombosis and stroke associated with tamoxifen use, although the mechanisms of increased risk remained unclear 5.
• A study published in Clinical Breast Cancer in 2006 found that the preponderance of clinical evidence suggested that tamoxifen increased stroke risk and had no effect or modestly reduced coronary heart disease risk 6.
• A more recent study published in JAMA Oncology in 2016 found that aromatase inhibitor-only users had a similar risk of stroke as tamoxifen-only users, although the risk of other cardiovascular disease events was increased in aromatase inhibitor users 7.

Key Findings

• Tamoxifen use may be associated with an increased risk of stroke, although the evidence is not consistent across all studies 3, 4, 5, 6, 7.
• The mechanisms of increased risk of stroke associated with tamoxifen use are not fully understood and require further research 5.
• The risk of stroke associated with tamoxifen therapy may vary depending on individual patient characteristics, such as age, menopausal status, and history of hypertension and diabetes 3, 4, 6, 7.