21-Gene Recurrence Score for prognosis and prediction of taxane benefit after adjuvant chemotherapy plus endocrine therapy: results from NSABP B-28/NRG Oncology

Abstract

Background: The 21-gene recurrence score (RS) predicts outcome and benefit from adjuvant chemotherapy benefit in breast cancer patients treated with adjuvant endocrine therapy. In the NSABP B-28 study, we evaluated the 21-gene RS for its prognostic impact and its ability to predict benefit from paclitaxel (P) in node-positive, estrogen receptor-positive (ER+) breast cancer patients treated with adjuvant chemotherapy plus tamoxifen.

Methods: The B-28 trial compared doxorubicin/cyclophosphamide (AC) with AC followed by P in 3060 patients. Tamoxifen for 5 years was also given to patients > 50 years and those < 50 years with ER+ and/or progesterone receptor-positive (PR+) tumors. The present study includes 1065 ER-positive, tamoxifen-treated patients with RS assessment. Median follow-up time was 11.2 years.

Results: In univariate analyses, RS was a significant predictor of outcome. In multivariate analyses, RS remained a significant independent predictor of outcome beyond clinico-pathologic factors, age, and type of surgery (p < 0.001). In the study population (n = 1065), the disease-free survival (DFS) hazard ratio (HR) with adding P to AC was 0.87 (95% CI 0.72-1.05; p = 0.14). RS was not a significant predictor of P benefit: for DFS, HRs for adding P to AC in RS low, intermediate, and high subgroups were 1.01 (95% CI 0.69-1.47; p = 0.99), 0.84 (95% CI 0.62-1.14; p = 0.26), and 0.81 (95% CI 0.60-1.10; p = 0.21), respectively (interaction p = 0.64). Similar findings were observed for the other study endpoints.

Conclusions: RS maintains significant prognostic impact in ER-positive, node-positive patients treated with adjuvant chemotherapy plus tamoxifen. However, RS did not significantly predict benefit from adding paclitaxel to AC chemotherapy. (Trial Registration: PDQ: NSABP-B-28).

Keywords: Breast cancer; Node-positive; Prognosis and prediction; Recurrence score.

Figures

Fig. 1

Comparison of (A) disease-free survival (DFS) and (B) distant relapse-free interval (DRFI) between 1,065 ER-positive, B-28 patients who were included in the present study and 999 ER-positive, B-28 patients who were excluded.

Fig. 2

Kaplan-Meier curves for (A) disease-free survival (DFS), (B) distant relapse-free interval (DRFI), (C) overall survival (OS), and (D) breast cancer-specific survival (BCSS) according to Recurrence Score categories: NSABP B-28

Fig. 3

Kaplan-Meier curves for disease-free survival (DFS) according to Recurrence Score categories: NSABP B-28

Fig. 4

Forest Plots of the effect of paclitaxel (P) according to Recurrence Score (RS) category: NSABP B-28