When is chemoprophylaxis for Tamoxifen (selective estrogen receptor modulator) appropriate?

Tamoxifen Chemoprophylaxis for Breast Cancer Risk Reduction

Tamoxifen chemoprophylaxis should be discussed as an option to reduce the risk of invasive breast cancer, specifically ER-positive breast cancer, in women who are ≥35 years of age with a 5-year projected absolute breast cancer risk ≥1.66% according to the NCI Breast Cancer Risk Assessment Tool, or with lobular carcinoma in situ (LCIS). 1

Optimal Candidates

• Premenopausal women aged 35 years or older with a 5-year projected absolute breast cancer risk ≥1.66% or with LCIS 1
• Postmenopausal women aged 35 years or older with a 5-year projected absolute breast cancer risk ≥1.66% or with LCIS 1
• Women with a personal history of atypical ductal hyperplasia 2
• The risk-benefit ratio is most favorable for women in their 40s at increased breast cancer risk without predisposition to thromboembolic events 2
• The risk-benefit ratio is most favorable for postmenopausal women without a uterus due to the increased risk of endometrial cancer with tamoxifen 2, 1

Contraindications

Tamoxifen is not recommended for use in:

• Women with a history of deep vein thrombosis or pulmonary embolism 1
• Women with a history of stroke or transient ischemic attack 1
• During prolonged immobilization 1
• Women who are pregnant, may become pregnant, or nursing mothers 1
• In combination with hormone therapy 1
• Women with known inherited clotting traits 1

Risk Factors for Thromboembolic Complications

Special caution should be exercised when considering tamoxifen in women with:

• Age ≥55 years 3
• Body mass index ≥25 kg/m² 3
• Elevated blood pressure 3
• Total cholesterol ≥250 mg/dL 3
• Current smoking 3
• Family history of coronary heart disease 3
• Concurrent chemotherapy (significantly increases thromboembolic risk) 4

Dosage and Duration

• The recommended dosage is 20 mg/day orally for 5 years 1
• The risk reduction benefit continues for at least 10 years after completing the 5-year treatment period 1

Monitoring During Treatment

• Follow-up should include a timely workup of abnormal vaginal bleeding 1
• Consider discontinuing tamoxifen prior to elective surgery and resuming when normal ambulation returns to reduce VTE risk 1, 5
• Periodic reassessment of breast cancer risk is recommended as risk increases with age 2

Potential Benefits and Risks

Benefits:

• Approximately 50% reduction in the risk of invasive ER-positive breast cancer 6
• Risk reduction benefit continues for at least 10 years after completing the 5-year treatment 1

Risks:

• Increased risk of endometrial cancer, particularly in women over 50 years 1
• Increased risk of thromboembolic events (deep vein thrombosis, pulmonary embolism) 1
• Hot flashes and other menopausal symptoms 1
• Increased risk of cataracts 1

Alternative Options

• For postmenopausal women, raloxifene (60 mg/day orally for 5 years) should be considered as an alternative to tamoxifen, particularly in women with an intact uterus due to lower risk of endometrial cancer 1
• Aromatase inhibitors (exemestane, anastrozole) may be considered as alternatives to tamoxifen for postmenopausal women 1
• Risk-reducing surgery may be appropriate for women at very high risk (e.g., BRCA mutation carriers) 1

Common Pitfalls to Avoid

• Failing to reassess breast cancer risk periodically as risk increases with age 2
• Recommending tamoxifen to women over 60 years without careful consideration of thromboembolic risk 2, 3
• Not discussing both the risks and benefits with each patient based on her individual risk factors 2
• Overlooking the long-term protective effect that continues after the 5-year treatment period 2
• Combining tamoxifen with concurrent chemotherapy, which significantly increases thromboembolic risk 4