As reported in the Journal of Clinical Oncology by Prudence A. Francis, MD, and colleagues, 12-year results of the phase III SOFT trial show a maintained disease-free survival benefit with the addition of ovarian function suppression to adjuvant tamoxifen in premenopausal patients with hormone receptor–positive breast cancer. Clinically meaningful absolute improvements in overall survival were observed with the addition of ovarian function suppression to tamoxifen or exemestane in subgroups of high-risk patients. 

Prudence A. Francis, MD

Study Details

In the trial, 3,047 patients were randomly assigned 1:1:1 to 5 years of tamoxifen plus ovarian function suppression (n = 1,015), exemestane plus ovarian function suppression (n = 1,014), or tamoxifen alone (n = 1,018). Ovarian suppression was achieved by use of intramuscular triptorelin, bilateral oophorectomy, or bilateral ovarian irradiation. Overall, 85% of patients had HER2-negative disease. The primary analysis compared disease-free survival with tamoxifen/ovarian function suppression vs tamoxifen alone; comparison of exemestane/ovarian function suppression vs tamoxifen was a secondary objective. Results at 5 years showed no disease-free survival benefit with the addition of ovarian function suppression to tamoxifen. At 8 years, tamoxifen/ovarian function suppression was associated with significant benefits in disease-free and overall survival. The current analysis presents outcomes after a median follow-up of 12 years.

Key Points

Disease-free survival at 12 years was 76.1% with tamoxifen/ovarian function suppression (hazard ratio [HR] vs tamoxifen = 0.82, 95% confidence interval [CI] = 0.69–0.98, P = .03), 79.0% with exemestane/ovarian function suppression (HR vs tamoxifen = 0.69, 95% CI = 0.57–0.83), and 71.9% with tamoxifen alone.

Overall survival at 12 years was 89.0% with tamoxifen/ovarian function suppression (HR vs tamoxifen = 0.78, 95% CI = 0.60–1.01, P = .06), 89.4% with exemestane/ovarian function suppression (HR vs tamoxifen = 0.80, 95% CI = 0.62–1.04), and 86.8% with tamoxifen.

Clinically meaningful absolute improvements in 12-year overall survival were observed in the tamoxifen/ovarian function suppression and exemestane/ovarian function suppression groups vs the tamoxifen alone group in subgroups associated with higher-risk clinical-pathologic features, including prior neoadjuvant chemotherapy (n = 333; 73.8% and 75.7% vs 60.9%), age younger than 35 years (n = 350; 82.8% and 79.1% vs 71.3%), and grade 3 tumors (n = 642; 80.8% and 84.0% vs 76.4%).

Among patients with HER2-negative disease who received prior chemotherapy, 12-year overall survival was 81.1% with tamoxifen/ovarian function suppression (n = 423; HR vs tamoxifen = 0.86, 95% CI = 0.63–1.17), 84.4% with exemestane/ovarian function suppression (n = 411; HR vs tamoxifen = 0.74, 95% CI = 0.53–1.03), and 78.8% with tamoxifen alone (n = 423). Among patients who did not receive prior chemotherapy, rates exceeded 95% in all three groups.

Proportions of patients remaining free of distant recurrence at 12 years were 86.2% with tamoxifen/ovarian function suppression (HR vs tamoxifen = 0.90, 95% CI = 0.71–1.14), 87.8% with exemestane/ovarian function suppression (HR vs tamoxifen = 0.75, 95% CI = 0.59–0.97), and 84.8% with tamoxifen.

The investigators concluded, “In conclusion, after 12 years, there remains a benefit from including [ovarian function suppression] in adjuvant endocrine therapy, with an absolute improvement in overall survival more apparent with higher baseline risk of recurrence.”

Dr. Francis, of the Department of Medical Oncology, Peter MacCallum Cancer Center, Melbourne, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Breast Cancer Trials Australia and New Zealand, National Cancer Research Institute Breast Clinical Studies Group, United Kingdom, US National Institutes of Health, and others. For full disclosures of the study authors, visit ascopubs.org.