In a study reported in the Journal of Clinical Oncology, Corey W. Speers, MD, PhD, and colleagues found that the sensitivity to endocrine therapy (SET2,3) index and the 21-gene breast recurrence score (RS) were not correlated in defining prognosis among postmenopausal patients with estrogen receptor (ER)-positive, node-positive breast cancer receiving adjuvant tamoxifen with or without chemotherapy in the SWOG S8814 trial. The SET2,3 index added prognostic information to RS but was not found to predict the benefit of chemotherapy.
As stated by the investigators, “Chemotherapy has not demonstrated benefit over adjuvant endocrine therapy alone for postmenopausal patients with node-positive breast cancer with an RS of 25 or below. We tested whether combined results from RS and the SET2,3 index of endocrine-related transcription (SETER/PR) adjusted for baseline prognostic index (BPI) improved prognostic assessment, and whether SET2,3 predicted benefit from anthracycline-based chemotherapy.”
Corey W. Speers, MD, PhD
Study Details
The study involved data from two arms of the SWOG S8814 trial (n = 283) comparing adjuvant anthracycline-based chemotherapy followed by 5 years of tamoxifen vs tamoxifen alone. The SET2,3 assay (high score = low risk) was calibrated and measured using whole-transcriptome RNA sequences of tumor samples that had been assessed for RS. The primary outcome measure was disease-free survival.
Key Findings
A total of 106 disease-free survival events occurred in the 283 patients over a median follow-up of 8.99 years. The proportional hazards assumption was not met beyond 5 years of follow-up; thus, the analysis was restricted to disease-free survival (57 events) during years 0 to 5.
The SET2,3 index and RS were not correlated (r = –0.04). In multivariate analysis adjusting for treatment, both were independently prognostic, with SET2,3 having a hazard ratio of 0.48 per unit (95% confidence interval [CI] = 0.34–0.68, P < .001) and RS having a hazard ratio of 1.28 per 10 units (95% CI = 1.14–1.44, P < .001).
The SET2,3 index did not predict chemotherapy benefit (P = .77 for interaction).
For 93 patients with high SET2,3 (low risk) among a total of 175 with RS ≤ 25, 5-year disease-free survival was 97%. For 55 patients with low SET2,3 (high risk) among a total of 108 with RS > 25, 5-year disease-free survival was 53%.
After adjustment for RS, both the SETER/PR (hazard ratio [HR] = 0.65, 95% CI= 0.46–0.92) and BPI (HR = 0.45, 95% CI= 0.31–0.64) components of the SET2,3 index were significantly associated with disease-free survival during years 0 to 5.
The investigators concluded, “SET2,3 index was not correlated with RS, demonstrated additive prognostic performance, and was not chemopredictive in this subset of patients from S8814. The SETER/PR and BPI components of SET2,3 each added prognostic information to RS.”
Dr. Speers, of the University of Michigan, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute and others. For full disclosures of the study authors, visit ascopubs.org.
