Background
Combined analysis of TEXT (N=2672) and SOFT (N=3066) phase III RCTs; 4690 premenopausal women with HR+ early breast cancer. TEXT compared exemestane+OFS vs tamoxifen+OFS. SOFT compared tamoxifen+OFS vs tamoxifen alone. 13-year follow-up (median) reported; represents the most mature endocrine therapy comparison in premenopausal patients.
Interventions and follow up
Arm A: Exemestane + ovarian function suppression (OFS: triptorelin, oophorectomy, or ovarian irradiation)
Arm B: Tamoxifen + OFS (TEXT/SOFT combined); tamoxifen alone (SOFT only arm)
Primary endpoint: Disease-free survival (DFS)
mFollow up: 13 year
Arm B: Tamoxifen + OFS (TEXT/SOFT combined); tamoxifen alone (SOFT only arm)
Primary endpoint: Disease-free survival (DFS)
mFollow up: 13 year
Results
DFS (exemestane+OFS vs tamoxifen+OFS): 12-yr DFS 75.2% vs 70.3%, HR 0.79, 95% CI 0.70–0.90
OS (exemestane+OFS vs tamoxifen+OFS): 12-yr OS 89.0% vs 88.0%, HR 0.93, 95% CI 0.78–1.11
DFS (tamoxifen+OFS vs tamoxifen alone, SOFT): 12-yr DFS 78.0% vs 71.4%, HR 0.76, 95% CI 0.62–0.93
OS (tamoxifen+OFS vs tamoxifen alone, SOFT): 12-yr OS 91.5% vs 87.4%, HR 0.67, 95% CI 0.48–0.92, P=.01
OS (exemestane+OFS vs tamoxifen+OFS): 12-yr OS 89.0% vs 88.0%, HR 0.93, 95% CI 0.78–1.11
DFS (tamoxifen+OFS vs tamoxifen alone, SOFT): 12-yr DFS 78.0% vs 71.4%, HR 0.76, 95% CI 0.62–0.93
OS (tamoxifen+OFS vs tamoxifen alone, SOFT): 12-yr OS 91.5% vs 87.4%, HR 0.67, 95% CI 0.48–0.92, P=.01
Adverse events
Exemestane+OFS: higher rates of bone loss/osteoporosis, arthralgia, vaginal dryness
Tamoxifen: higher rates of thromboembolic events and hot flashes in younger patients
OFS-associated: menopausal symptoms, mood/cognitive effects reported in SOFT quality-of-life substudy
Tamoxifen: higher rates of thromboembolic events and hot flashes in younger patients
OFS-associated: menopausal symptoms, mood/cognitive effects reported in SOFT quality-of-life substudy
Conclusions
At 13-year follow-up, exemestane+OFS demonstrated superior DFS vs tamoxifen+OFS in premenopausal HR+ early BC. OFS added to tamoxifen significantly improved OS vs tamoxifen alone in the SOFT trial. Greatest benefits seen in patients under 35 and those who received prior chemotherapy.
Key Limitations
Key Limitations: OS differences for exemestane+OFS vs tamoxifen+OFS remain non-significant despite longer follow-up — DFS serves as surrogate. Quality-of-life impact of OFS is substantial and not fully captured in efficacy-focused analyses; patient selection for OFS requires careful shared decision-making. OFS delivery method varied (GnRH agonist vs surgery vs irradiation) across sites. The highest-risk patients (prior chemo, age <35) derive greatest benefit, suggesting OFS is not universally necessary in lower-risk premenopausal patients.
Clinical Context
TEXT/SOFT established OFS + AI (exemestane) as preferred adjuvant endocrine therapy in high-risk premenopausal HR+ BC, per ASCO and ESMO guidelines. OFS + tamoxifen is an alternative for intermediate-risk patients or those intolerant to AI. ESMO-MCBS score (exemestane+OFS vs tamoxifen): 3. The survival benefit in SOFT (tamoxifen+OFS vs alone) has since supported broader OFS use in premenopausal patients receiving adjuvant chemotherapy.