What is the recommended dose and duration of raloxifene (Selective Estrogen Receptor Modulator) for chemoprevention in a patient with a CHEK2 mutation?

Raloxifene Dosing for Breast Cancer Chemoprevention

For chemoprevention, raloxifene should be prescribed at 60 mg per day orally for 5 years in postmenopausal women with a CHEK2 mutation who are at increased risk of breast cancer. 1

Dosing and Duration Algorithm

1. Standard Dosage: 60 mg per day orally 1, 2
2. Duration: 5 years 1
3. Patient Population:
   • Postmenopausal women only
   • Age ≥35 years
   • With 5-year projected breast cancer risk ≥1.66% (using NCI Breast Cancer Risk Assessment Tool) or with LCIS
   • CHEK2 mutation carriers fall into high-risk category

Extended Use Considerations

• Raloxifene may be used longer than 5 years in women who also have osteoporosis, where breast cancer risk reduction becomes a secondary benefit 1
• The optimal duration beyond 5 years is not established in clinical trials 1

Efficacy

• Reduces risk of invasive breast cancer by 76% during 3 years of treatment 3
• Particularly effective for ER-positive breast cancers (90% risk reduction) 3
• After 4 years of treatment, shows 72% risk reduction in invasive breast cancer 4
• Approximately 93-126 women need to be treated for 4 years to prevent one case of invasive breast cancer 3, 4

Contraindications and Precautions

Raloxifene should NOT be prescribed in:

• Premenopausal women 1
• Women with history of:
  • Deep vein thrombosis
  • Pulmonary embolism
  • Stroke
  • Transient ischemic attack
  • During prolonged immobilization 1, 2

Important Monitoring Considerations

• Baseline and regular mammograms should continue according to standard screening guidelines 2
• Monitor for signs of venous thromboembolism, which occurs more frequently with raloxifene (3.1 times higher risk than placebo) 3
• The risk of thromboembolic events is highest in the first 4 months of treatment 2
• Discontinue raloxifene at least 72 hours before prolonged immobilization (e.g., surgery) 2

Clinical Pearls

• Raloxifene has a more favorable side effect profile than tamoxifen regarding endometrial cancer risk 5
• Raloxifene causes fewer cataracts than tamoxifen 5
• Calcium (1500 mg/day) and vitamin D (400-800 IU daily) supplementation should be considered alongside raloxifene therapy 2
• For CHEK2 mutation carriers specifically, while direct evidence is limited, they fall into the high-risk category that benefits from chemoprevention

Common Pitfalls to Avoid

• Using raloxifene in premenopausal women (ineffective and inappropriate) 1
• Prescribing to women with history of thromboembolic events 2
• Failing to discontinue before prolonged immobilization 2
• Not providing adequate calcium/vitamin D supplementation 2
• Using for prevention of non-invasive breast cancer (not indicated) 2
• Assuming protection against ER-negative breast cancers (benefit primarily for ER-positive cancers) 3

Remember that raloxifene does not eliminate breast cancer risk entirely, and regular screening should continue throughout treatment.