Long-Term Use of Raloxifene in Postmenopausal Women
Raloxifene may be used longer than 5 years in postmenopausal women with osteoporosis, in whom breast cancer risk reduction is a secondary benefit. 1 This recommendation is supported by clinical evidence showing continued efficacy and acceptable safety profile with extended use.
Indications for Long-Term Raloxifene Use
Raloxifene (60 mg daily) is FDA-approved for:
- Treatment and prevention of osteoporosis in postmenopausal women
- Reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis
- Reduction in risk of invasive breast cancer in postmenopausal women at high risk 2
Duration of Therapy
While the standard recommendation for breast cancer risk reduction is 5 years, longer duration may be appropriate in specific circumstances:
- Osteoporosis management: When used primarily for osteoporosis, longer-term use beyond 5 years is supported by clinical evidence 1
- Breast cancer risk reduction: The optimal duration for this indication is not definitively established 2
Efficacy with Long-Term Use
Bone Health Benefits
- Maintains bone mineral density (BMD) with continued use 3
- Relative risk reduction for vertebral fractures continues during extended therapy 3
- Bone turnover markers remain in the premenopausal reference interval 3
- Bone biopsies after 8 years of therapy show normal bone and bone cells 3
Breast Cancer Risk Reduction
- The benefit in reducing invasive breast cancer risk increases with greater duration of therapy up to 8 years 3
- Specifically reduces risk of estrogen receptor (ER)-positive invasive breast cancer 1
Safety Considerations for Long-Term Use
Contraindications
Raloxifene should not be used in women with:
- History of deep vein thrombosis
- Pulmonary embolism
- Stroke
- Transient ischemic attack
- During prolonged immobilization 1
Adverse Effects
- Venous thromboembolism: Increased risk (black box warning) 2
- Stroke: Increased risk of fatal stroke in women with documented coronary heart disease or at increased risk for major coronary events 2
- Hot flushes: May be accentuated in early menopause 1
- Other side effects: Leg cramps, peripheral edema, and gallbladder disease 1
Special Considerations
Combination Therapy
- Not recommended with aromatase inhibitors based on decreased efficacy seen with tamoxifen/anastrozole combinations 1
- Not recommended with hormone therapy 1
Patient Selection for Long-Term Use
Best candidates for long-term raloxifene therapy are:
- Postmenopausal women ≥35 years old
- Women with osteoporosis requiring ongoing treatment
- Women with 5-year projected breast cancer risk ≥1.66% or with LCIS
- Women without contraindications to therapy 1
Monitoring During Long-Term Therapy
- Regular bone mineral density testing
- Breast exams and mammograms should continue in keeping with good medical practice 2
- Calcium (1500 mg/day) and vitamin D (400-800 IU daily) supplementation should be maintained 2
- Vigilance for symptoms of venous thromboembolism
Clinical Perspective
The decision for long-term raloxifene use should balance the dual benefits of osteoporosis management and breast cancer risk reduction against the potential risks of venous thromboembolism and stroke. For postmenopausal women with osteoporosis who also have elevated breast cancer risk, the benefit-risk ratio generally favors continued use beyond 5 years 4.
For women using raloxifene primarily for breast cancer risk reduction without osteoporosis, the standard 5-year duration is recommended, as there is less evidence supporting longer-term use for this indication alone 1.