When Raloxifene is Used
Raloxifene is FDA-approved for three specific indications in postmenopausal women: (1) treatment and prevention of osteoporosis, (2) reduction of invasive breast cancer risk in those with osteoporosis, and (3) reduction of invasive breast cancer risk in those at high risk for breast cancer. 1
Primary Indications
Osteoporosis Management in Postmenopausal Women
Raloxifene 60 mg daily is indicated for both prevention and treatment of postmenopausal osteoporosis, demonstrating significant reductions in vertebral fracture risk (30-50% reduction over 36 months) and increases in bone mineral density at the lumbar spine (1.6-3.4%), femoral neck (0.9-2.3%), and total hip (1.0-1.6%). 2, 1, 3
The drug reduces vertebral fracture risk in women with established osteoporosis regardless of whether they have existing fractures at baseline. 3, 4
Important limitation: Raloxifene has NOT been shown to reduce non-vertebral or hip fracture risk, making it less potent than bisphosphonates for comprehensive fracture prevention. 2, 5
Breast Cancer Risk Reduction
Raloxifene reduces invasive breast cancer risk by 72% after 4 years of treatment in postmenopausal women with osteoporosis, with the number needed to treat being 93 women for 4 years to prevent one case. 6
The drug specifically reduces estrogen receptor-positive invasive breast cancer by 84% (RR 0.16,95% CI 0.09-0.30) but has no effect on estrogen receptor-negative cancers. 2, 6
FDA approval extends to postmenopausal women at high risk for breast cancer, defined as 5-year predicted risk ≥1.66% by the Gail model, one or more first-degree relatives with breast cancer, or history of lobular carcinoma in situ (LCIS) or atypical hyperplasia. 1
Clinical Decision Algorithm
When to Consider Raloxifene
Ideal candidates are postmenopausal women who benefit from dual protection: those with both osteoporosis/low bone density AND elevated breast cancer risk. 2, 5
Specific Patient Selection Criteria
Age ≥35 years and postmenopausal status (raloxifene is contraindicated in premenopausal women as it decreases BMD in this population). 2
5-year projected breast cancer risk ≥1.66% according to the NCI Breast Cancer Risk Assessment Tool (Gail model). 2
Women with osteoporosis who primarily need vertebral fracture protection and desire breast cancer risk reduction as a secondary benefit. 2, 1
Absolute Contraindications
Active or history of venous thromboembolism (DVT/PE) - raloxifene increases VTE risk 3.1-fold compared to placebo. 2, 1, 3
History of stroke or transient ischemic attack - increased risk of fatal stroke (HR 1.49) demonstrated in high-risk populations. 2
Premenopausal women or those with prolonged immobilization. 2
Women with a history of breast cancer (raloxifene is NOT indicated for treatment or recurrence prevention). 1
Important Clinical Caveats
Limitations in Breast Cancer Populations
Raloxifene should NOT be used in women with a history of breast cancer for osteoporosis management - bisphosphonates are the preferred first-line agents in this population due to superior anti-fracture efficacy and established safety. 2, 7
The National Comprehensive Cancer Network specifically recommends against raloxifene following 5 years of tamoxifen adjuvant therapy due to concerns about cross-resistance and potential tumor stimulation. 7
Raloxifene has limited anti-tumor activity against established breast cancer when used after tamoxifen. 7
Comparison to Alternative Agents
Raloxifene is less potent than bisphosphonates for osteoporosis treatment, particularly for non-vertebral fracture prevention. 2
Unlike tamoxifen, raloxifene does NOT reduce noninvasive breast cancer risk. 1
Raloxifene causes significantly less vaginal bleeding (≤6.4%) compared to hormone replacement therapy (50-88%) and has no endometrial stimulation. 3
Common Adverse Effects
Hot flashes, leg cramps, peripheral edema, and influenza-like symptoms are common, which may be particularly problematic in early menopause. 2, 3
Deep venous thrombosis occurs in 0.7% (vs 0.2% placebo) and pulmonary embolism in 0.3% (vs 0.1% placebo). 2
Increased risk of fatal stroke in women with coronary artery disease or cardiovascular risk factors. 2, 1
Dosing and Duration
Standard dose: 60 mg orally once daily, which may be taken at any time without regard to meals. 1
For breast cancer risk reduction, optimal treatment duration is unknown - the pivotal trial had a median follow-up of 4.3 years with only 27% of participants receiving drug for 5 years. 1
Raloxifene may be used longer than 5 years in women with osteoporosis where breast cancer risk reduction is a secondary benefit. 2