Prediction of Risk of Distant Recurrence Using the 21-Gene Recurrence Score in Node-Negative and Node-Positive Postmenopausal Patients With Breast Cancer Treated With Anastrozole or Tamoxifen: A TransATAC Study

Abstract

PURPOSE To determine whether the Recurrence Score (RS) provided independent information on risk of distant recurrence (DR) in the tamoxifen and anastrozole arms of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trial. PATIENTS AND METHODS RNA was extracted from 1,372 tumor blocks from postmenopausal patients with hormone receptor-positive primary breast cancer in the monotherapy arms of ATAC. Twenty-one genes were assessed by quantitative reverse transcriptase polymerase chain reaction, and the RS was calculated. Cox proportional hazards models assessed the value of adding RS to a model with clinical variables (age, tumor size, grade, and treatment) in node-negative (N0) and node-positive (N+) women. RESULTS Reportable scores were available from 1,231 evaluable patients (N0, n = 872; N+, n = 306; and node status unknown, n = 53); 72, 74, and six DRs occurred in N0, N+, and node status unknown patients, respectively. For both N0 and N+ patients, RS was significantly associated with time to DR in multivariate analyses (P < .001 for N0 and P = .002 for N+). RS also showed significant prognostic value beyond that provided by Adjuvant! Online (P < .001). Nine-year DR rates in low (RS < 18), intermediate (RS = 18 to 30), and high RS (RS > or = 31) groups were 4%, 12%, and 25%, respectively, in N0 patients and 17%, 28%, and 49%, respectively, in N+ patients. The prognostic value of RS was similar in anastrozole- and tamoxifen-treated patients. CONCLUSION This study confirmed the performance of RS in postmenopausal HR+ patients treated with tamoxifen in a large contemporary population and demonstrated that RS is an independent predictor of DR in N0 and N+ hormone receptor-positive patients treated with anastrozole, adding value to estimates with standard clinicopathologic features.

Distinguishing luminal breast cancer subtypes by Ki67, progesterone receptor or TP53 status provides prognostic information

“…The recurrence score has been shown to correlate with risk of both loco-regional 23 and distant recurrence in ER-positive, node-negative breast cancer. 24,25 Furthermore, this 21 multigene assay is predictive of treatment response to endocrine therapy when the recurrence score is low and to chemotherapy when the recurrence score is high. 26,27 Proliferation-related genes receive the highest weighting in the algorithm and consequently make the greatest contribution to the determination of the recurrence score.…”

Breast Cancer Genomics: Challenges in Interpretation and Application

“…Two recent studies showed that patients with node-positive and ER-positive breast cancer had clinically significant (Ͼ10%) risk of relapse for any 21-gene recurrence score class [5,9]. In one study, the low or intermediate recurrence score identified a subset of patients for whom chemotherapy offered no significant benefit over tamoxifen alone, but the recurrence score failed to identify any subset with excellent survival from either treatment arm [5].…”

Optimal Systemic Therapy for Early Breast Cancer in Women: A Clinical Practice Guideline

“…The test is most useful in patients with hormone receptor-positive, her2-negative, lymph node-negative cancer. Studies have retrospectively evaluated the use of Oncotype dx in patients with lymph node-positive cancer, but those studies are not entirely robust from a statistical standpoint 19,20 .…”