What is the treatment plan for patients in the TARGET (TAMoxifen And Raloxifene Generating Evidence for a Trial) trial?

TARGET Trial: Tamoxifen and Raloxifene for Breast Cancer Risk Reduction

Treatment Arms

The TARGET trial, more formally known as the STAR (Study of Tamoxifen And Raloxifene) trial, compared two selective estrogen receptor modulators (SERMs) for breast cancer risk reduction in postmenopausal women at increased risk. 1

Eligibility Criteria

• Postmenopausal women aged ≥35 years with increased risk of breast cancer (5-year Gail model risk ≥1.66%) 1
• Women with history of lobular carcinoma in situ (LCIS) or atypical hyperplasia were included 1
• Key exclusions: history of deep vein thrombosis, pulmonary embolism, stroke, or concurrent hormone therapy 1, 2

Treatment Regimens

The trial randomized participants to one of two arms:

Tamoxifen Arm

• Dosing: 20 mg orally daily for 5 years 2
• Reduces risk of estrogen receptor (ER)-positive invasive breast cancer 2
• Appropriate for both premenopausal and postmenopausal women, though STAR enrolled only postmenopausal women 2

Raloxifene Arm

• Dosing: 60 mg orally daily for 5 years 2
• Postmenopausal women only 2
• More favorable side effect profile with lower risk of thromboembolic events, endometrial cancer, and cataracts compared to tamoxifen 2

Key Trial Outcomes

Efficacy Results

At 81 months median follow-up, raloxifene proved 76% as effective as tamoxifen in reducing overall invasive breast cancer risk (RR 1.24; 95% CI, 1.05-1.47). 1 At the initial 47-month analysis, raloxifene was equally effective as tamoxifen for overall breast cancer reduction (RR 1.02; 95% CI, 0.82-1.28) and ER-positive tumors (RR 0.93; 95% CI, 0.72-1.24). 1

Safety Profile

Raloxifene demonstrated superior tolerability with fewer adverse events: 1

• Lower incidence of thromboembolic events compared to tamoxifen
• Reduced endometrial cancer risk versus tamoxifen
• Fewer cataracts than tamoxifen
• Similar risks for ischemic heart disease, fractures, and stroke between arms

Both agents share common contraindications and risks: 2

• Increased thromboembolic events (raloxifene OR 1.63; CI 1.36-1.98) 1
• Pulmonary embolism risk (raloxifene OR 1.82; CI 1.16-2.92) 1
• Hot flashes (raloxifene OR 1.58; CI 1.35-1.84) 1
• Cerebrovascular death (raloxifene OR 1.56; CI 1.04-2.39) 1

Critical Clinical Considerations

Treatment Duration

Both medications should be limited to 5 years duration outside of clinical trials. 2 Evidence shows that more than 5 years of tamoxifen does not further reduce breast cancer recurrence and doubles endometrial cancer risk. 3

Sequential Therapy Warning

Raloxifene should NOT be used following 5 years of tamoxifen therapy. 1, 3 Laboratory and animal studies demonstrate that raloxifene may stimulate tamoxifen-dependent cells and has similar stimulatory effects on breast and endometrial tumors previously exposed to long-term tamoxifen. 3 This combination is specifically not recommended by ASCO guidelines. 2

Concurrent Use Prohibition

Tamoxifen and raloxifene must never be taken together. 2 These are alternative options to each other, not complementary therapies, with no evidence supporting combined use for breast cancer risk reduction. 2

Risk Assessment Requirements

Women should have documented increased breast cancer risk using validated tools (Gail model 5-year risk ≥1.66% or equivalent) before initiating therapy. 1 The CARE model provides more accurate estimates for African American women. 1