Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20

Abstract

Purpose: The 21-gene OncotypeDX recurrence score (RS) assay quantifies the risk of distant recurrence in tamoxifen-treated patients with node-negative, estrogen receptor (ER)-positive breast cancer. We investigated the association between RS and risk for locoregional recurrence (LRR) in patients with node-negative, ER-positive breast cancer from two National Surgical Adjuvant Breast and Bowel Project (NSABP) trials (NSABP B-14 and B-20).

Patients and methods: RS was available for 895 tamoxifen-treated patients (from both trials), 355 placebo-treated patients (from B-14), and 424 chemotherapy plus tamoxifen-treated patients (from B-20). The primary end point was time to first LRR. Distant metastases, second primary cancers, and deaths before LRR were censored.

Results: In tamoxifen-treated patients, LRR was significantly associated with RS risk groups (P < .001). The 10-year Kaplan-Meier estimate of LRR was 4.% (95% CI, 2.3% to 6.3%) for patients with a low RS (< 18), 7.2% (95% CI, 3.4% to 11.0%) for those with intermediate RS (18-30), and 15.8% (95% CI, 10.4% to 21.2%) for those with a high RS (> 30). There were also significant associations between RS and LRR in placebo-treated patients from B-14 (P = .022) and in chemotherapy plus tamoxifen-treated patients from B-20 (P = .028). In multivariate analysis, RS was an independent significant predictor of LRR along with age and type of initial treatment.

Conclusion: Similar to the association between RS and risk for distant recurrence, a significant association exists between RS and risk for LRR. This information has biologic consequences and potential clinical implications relative to locoregional therapy decisions for patients with node-negative and ER-positive breast cancer.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

CONSORT diagram for patients from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14 and B-20 trials. (*) Methotrexate and fluorouracil with leucovorin rescue (MFT): 203 patients; tamoxifen plus cyclophosphamide, methotrexate, and fluorouracil (CMFT): 221 patients. IBC, invasive breast cancer; RT-PCR, reverse transcription polymerase chain reaction; TAM, tamoxifen; chemo, chemotherapy.

Fig 2.

(A) Kaplan-Meier estimates of the proportion of B-14 and B-20 tamoxifen-treated patients with locoregional recurrence at 10 years according to the three recurrence score (RS) categories. (B) Kaplan-Meier estimates of the proportion of B-14 placebo-treated patients with locoregional recurrence at 10 years according to the three RS categories. (C) Kaplan-Meier estimates of the proportion of B-20 chemotherapy plus tamoxifen-treated patients with locoregional recurrence at 10 years according to the three RS categories.

Fig 3.

Percentage of patients with locoregional recurrence (LRR) at 10 years according to various subgroups in the 895 tamoxifen-treated patients in National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14/B-20 trials. RS, recurrence score.

Fig 4.

Ten-year Kaplan-Meier estimates of the proportions of locoregional recurrence (LRR) according to recurrence score (RS), initial locoregional treatment, and age in the 895 tamoxifen-treated patients in National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14/B-20 trials. XRT, radiation therapy.