Long-term outcomes on the addition of OFS to endocrine therapy in HR+ early breast cancer

March 2023 Cancer trials Andrea Enguita

Previous results from the SOFT trial demonstrated that the addition of ovarian function suppression (OFS) to tamoxifen reduces the recurrence risk and improves the survival of premenopausal women with hormone receptor-positive (HR+) early breast cancer (EBC). The 12-year updated analysis of this trial, recently published in the Journal of Clinical Oncology, showed that the reduced recurrence risk and survival benefit of adding OFs to endocrine therapy is maintained during this extended period.

Women with hormone receptor-positive (HR+) early breast cancer (EBC) have a high risk of disease recurrence. Interestingly, this risk of recurrence is lower in premenopausal women who develop amenorrhea after chemotherapy. Based on this observation, the international Suppression of Ovarian Function Trial (SOFT) assessed whether combining standard tamoxifen (TAM) therapy with ovarian function suppression (OFS) could improve survival outcomes in patients with HR+ EBC, and whether combining OFS with the aromatase inhibitor exemestane (EXE) could further improve these outcomes. While the benefit of adding OFS to TAM was not clear at 5 years, the TAM+OFS combination led to a significant reduction in recurrence and improved overall survival (OS) after 8 years compared to TAM alone. The 12-year update results of SOFT were recently published in the Journal of Clinical Oncology.

Study findings

The phase 3 SOFT trial enrolled 3,074 premenopausal women with HR+ EBC who were randomly assigned (1:1:1) to receive 5 years of adjuvant TAM, TAM+OFS, or EXE+OFS. The primary analysis compared disease-free survival (DFS) between TAM+OFS vs. TAM alone, while EXE+OFS vs. TAM was a secondary objective.

After 12 years of follow-up, DFS continues to favour TAM+OS vs. TAM alone (HR[95%CI]: 0.82[0.69-0.98]). DFS rates at 12 years were 71.9% with TAM, 76.1% with TAM+OFS, and 79.0% with EXE+ OFS. Additionally, also the OS was improved with TAM+ OFS vs. TAM (HR[95%CI]: 0.78[0.60-1.01]). At the 12-year landmark, this translates into OS rates of 86.8% for TAM and 89.0% with TAM+ OFS. For EXE+OFS, the 12-year OS rate was reported at 89.4%. Among patients who received prior chemotherapy for human epidermal growth factor receptor-2-negative tumours, OS was 78.8% with TAM, 81.1% with TAM+ OFS, and 84.4% with EXE+ OFS.

These 12-year findings suggest that the benefit of adding OFS to TAM or EXE prevails in time, improving long-term survival and lowering the risk of recurrence in premenopausal women with HR+ EBC cancer.


Francis PA, Fleming GF, Láng I, et al. Adjuvant Endocrine Therapy in Premenopausal Breast Cancer: 12-Year Results From SOFT. J Clin Oncol. 2023;41(7): 1370-5.