The final 15-year results of the SOFT and TEXT trials confirm that escalating endocrine therapy reduces recurrence in premenopausal women with hormone-sensitive early breast cancer, but that the clear survival gain is concentrated in the highest-risk subgroups.
What was known
In premenopausal women with hormone receptor-positive early breast cancer, SOFT had shown that adding ovarian function suppression (OFS) to tamoxifen reduces recurrence, and that exemestane plus OFS reduces it further.
What this work adds
This is the final 15-year analysis of two phase III randomised trials: SOFT, with 3,047 women in the intention-to-treat population, and TEXT, with 2,660. SOFT compared five years of tamoxifen with tamoxifen plus OFS and with exemestane plus OFS; TEXT compared tamoxifen plus OFS with exemestane plus OFS. Chemotherapy was optional; endpoints included breast cancer-free interval, distant recurrence-free interval and overall survival.
Main results
In SOFT, escalating endocrine therapy continued to reduce recurrence: the 15-year breast cancer-free interval was 78.6% with exemestane plus OFS, 75.7% with tamoxifen plus OFS and 72.1% with tamoxifen alone (tamoxifen plus OFS versus tamoxifen: hazard ratio 0.82; 95% confidence interval 0.69-0.98; p=0.03). In the cohort that received no chemotherapy, OFS reduced breast cancer events at 15 years, with high overall survival in all groups. Among women with HER2-negative tumours previously treated with chemotherapy (n=1,257), 15-year overall survival was 81.0% with exemestane plus OFS, 77.1% with tamoxifen plus OFS and 76.8% with tamoxifen alone; in women under 35 years of age (n=241) it was 82.5%, 77.9% and 68.1%, respectively. In the combined analysis, among patients with HER2-negative tumours (n=4,035), exemestane plus OFS versus tamoxifen plus OFS reduced distant recurrence (hazard ratio 0.75; 95% confidence interval 0.63-0.90), with a smaller reduction in deaths (hazard ratio 0.89; 95% confidence interval 0.74-1.06). Absolute benefits were larger the worse the risk features, particularly young age and high tumour grade.
What it means
The authors conclude that the meaningful overall survival benefit of exemestane and/or ovarian suppression, compared with tamoxifen alone, is limited to high-risk premenopausal subgroups with HER2-negative breast cancer, and that tamoxifen alone may not be optimal in high-grade HER2-negative tumours. In practice, choosing between tamoxifen, tamoxifen with OFS and exemestane with OFS requires weighing age, tumour grade, previous treatment and individual risk, and balancing the expected gain against side effects.
Reference: Francis PA, Pagani O, Fleming GF, Walley BA, Colleoni M, Rubovszky G, et al. Final outcomes of the SOFT and TEXT phase III trials in premenopausal hormone receptor-positive early breast cancer. Annals of Oncology, 2026. https://doi.org/10.1016/j.annonc.2026.05.704
