Comparison of the prognostic and predictive utilities of the 21-gene Recurrence Score assay and Adjuvant! for women with node-negative, ER-positive breast cancer: results from NSABP B-14 and NSABP B-20

Abstract

The Oncotype DX Recurrence Score (RS) is a validated genomic predictor of outcome and response to adjuvant chemotherapy in ER-positive breast cancer. Adjuvant! was developed using SEER registry data and results from the Early Breast Cancer Clinical Trialists' overview analyses to estimate outcome and benefit from adjuvant hormonal therapy and chemotherapy. In this report we compare the prognostic and predictive utility of these two tools in node-negative, ER-positive breast cancer. RS and Adjuvant! results were available from 668 tamoxifen-treated NSABP B-14 patients, 227 tamoxifen-treated NSABP B-20 patients, and 424 chemotherapy plus tamoxifen-treated B-20 patients. Adjuvant! results were also available from 1952 B-20 patients. The primary endpoint was distant recurrence-free interval (DRFI). Cox proportional hazards models were used to compare the prognostic and predictive utility of RS and Adjuvant!. Both RS (P < 0.001) and Adjuvant! (P = 0.002) provided strong independent prognostic information in tamoxifen-treated patients. Combining RS and individual clinicopathologic characteristics provided greater prognostic discrimination than combining RS and the composite Adjuvant!. In the B-20 cohort with RS results (n = 651), RS was significantly predictive of chemotherapy benefit (interaction P = 0.031 for DRFI, P = 0.011 for overall survival [OS], P = 0.082 for disease-free survival [DFS]), but Adjuvant! was not (interaction P = 0.99, P = 0.311, and P = 0.357, respectively). However, in the larger B-20 sub-cohort (n = 1952), Adjuvant! was significantly predictive of chemotherapy benefit for OS (interaction P = 0.009) but not for DRFI (P = 0.219) or DFS (P = 0.099). Prognostic estimates can be optimized by combining RS and clinicopathologic information instead of simply combining RS and Adjuvant!. RS should be used for estimating relative chemotherapy benefit.

Fig. 1

CONSORT diagram for patients from the National Surgical Adjuvant Breast and Bowel Project B-14 and B-20 trials. Abbreviations: IBC, invasive breast cancer; RT-PCR, Reverse transcription polymerase chain reaction; TAM, tamxifen; chemo, chemotherapy. *Includes 290 randomized and 378 registered patients. ^†Tamoxifen plus methotrexate and fluorouracil (MFT): 203 patients; tamoxifen plus. cyclophosphamide, methotrexate, and fluorouracil (CMFT): 221 patients.

Fig. 2

Scatter plot of RS and the Adjuvant! RI.

Fig. 3

Point estimates and 95% confidence intervals for the percentage of B-14 patients with distant recurrence at 10 years by RS and RI risk groups.

Fig. 4

Kaplan-Meier curves for distant recurrence in 651 B-20 patients.

Fig. 5

Association among the three Adjuvant! RIs based on three independent pathologic gradings (grade #2 was from the pathologist in Standard University). Because of its discrete nature, each point may represent multiple patients.

Fig. 5

Association among the three Adjuvant! RIs based on three independent pathologic gradings (grade #2 was from the pathologist in Standard University). Because of its discrete nature, each point may represent multiple patients.

Fig. 5

Association among the three Adjuvant! RIs based on three independent pathologic gradings (grade #2 was from the pathologist in Standard University). Because of its discrete nature, each point may represent multiple patients.