21-Gene Recurrence Score and Locoregional Recurrence in Node-Positive/ER-Positive Breast Cancer Treated With Chemo-Endocrine Therapy

Abstract

Background: The 21-gene recurrence score (RS) predicts risk of locoregional recurrence (LRR) in node-negative, estrogen receptor (ER)-positive breast cancer. We evaluated the association between RS and LRR in node-positive, ER-positive patients treated with adjuvant chemotherapy plus tamoxifen in National Surgical Adjuvant Breast and Bowel Project B-28. Methods: B-28 compared doxorubicin/cyclophosphamide (AC X 4) with AC X 4 followed by paclitaxel X 4. Tamoxifen was given to patients age 50 years or older and those younger than age 50 years with ER-positive and/or progesterone receptorpositive tumors. Lumpectomy patients received breast radiotherapy. Mastectomy patients received no radiotherapy. The present study includes 1065 ER-positive, tamoxifen-treated patients with RS assessment. Cumulative incidence functions and subdistribution hazard regression models were used for LRR to account for competing risks including distant recurrence, second primary cancers, and death from other causes. Median follow-up was 11.2 years. All statistical tests were one-sided. Results: There were 80 LRRs (7.5%) as first events (68% local/32% regional). RS was low: 36.2%; intermediate: 34.2%; and high: 29.6%. RS was a statistically significant predictor of LRR in univariate analyses (10-year cumulative incidence of LRR ¼ 3.3%, 7.2%, and 12.2% for low, intermediate, and high RS, respectively, P < .001). In multivariable regression analysis, RS remained an independent predictor of LRR (hazard ratio [HR] ¼ 2.59, 95% confidence interval [CI] ¼ 1.28 to 5.26, for a 50-point difference, P ¼ .008) along with pathologic nodal status (HR ¼ 1.91, 95% CI ¼ 1.20 to 3.03, for four or more vs one to three positive nodes, P ¼ .006) and tumor size (HR ¼ 1.28, 95% CI ¼ 1.05 to 1.55, for a 1 cm difference, P ¼ .02). Conclusions: RS statistically significantly predicts risk of LRR in node-positive, ER-positive breast cancer patients after adjuvant chemotherapy plus tamoxifen. These findings can help in the selection of appropriate candidates for comprehensive radiotherapy.

Prospective Evaluation of the Impact of the 21-Gene Recurrence Score Assay on Adjuvant Treatment Decisions for Women with Node-Positive Breast Cancer in Ontario, Canada

“…In the cohort of patients with node‐positive disease who participated in the NSABP B‐28 trial and received tamoxifen plus adjuvant chemotherapy (randomized to docetaxel, doxorubicin, and cyclophosphamide or dose‐dense doxorubicin and cyclophosphamide followed by dose‐dense paclitaxel [dd AC‐P] or dd AC‐P with gemcitabine added to paclitaxel), the RS result was shown to be a significant predictor of outcome for disease‐free and overall survival, distant recurrence‐free interval, and breast cancer‐specific survival. Multivariable analysis showed that the RS result was independent of other prognostic indicators, including the number of nodes, tumor size, tumor grade, treatment, and whether or not the patient had a mastectomy .…”

Trends and variations in postmastectomy radiation therapy for breast cancer in patients with 1 to 3 positive lymph nodes: A National Cancer Data Base analysis

“…6,8 According to a recent analysis of outcomes in patients with ER-positive breast cancer who underwent mastectomy without PMRT for 1 to 3 positive lymph nodes in National Surgical Adjuvant Breast and Bowel Project trial NSABP B-28, the locoregional recurrence rate was only 6% in the subset with high Oncotype Dx (Genomic Health, Inc, Redwood City, CA) recurrence scores, and was even lower for subsets with lower recurrence scores. 11 These data suggest that biologic factors may help to identify women who will derive a greater benefit from PMRT than others. However, a lack of consistency in identifying these subsets in the era of modern surgical and systemic therapies has likely resulted in highly variable treatment patterns across the United States.…”

“…Despite the randomized trial evidence in support of PMRT, large single‐institution series have demonstrated low rates of locoregional recurrence in low‐risk subsets of patients with 1 to 3 positive lymph nodes, ranging from 2% to 5% at 5 years . According to a recent analysis of outcomes in patients with ER‐positive breast cancer who underwent mastectomy without PMRT for 1 to 3 positive lymph nodes in National Surgical Adjuvant Breast and Bowel Project trial NSABP B‐28, the locoregional recurrence rate was only 6% in the subset with high Oncotype Dx (Genomic Health, Inc, Redwood City, CA) recurrence scores, and was even lower for subsets with lower recurrence scores . These data suggest that biologic factors may help to identify women who will derive a greater benefit from PMRT than others.…”

Summary of head‐to‐head comparisons of patient risk classifications by the 21‐gene Recurrence Score® (RS) assay and other genomic assays for early breast cancer

“…Prediction of prognosis in chemotherapy‐treated patients was validated for the RS in the NASBP B28, PCAS‐01, for Prosigna in the DBCG77B trial . and for Endopredict in the GEICAM/9906 trials . The prognostic power of Mammaprint in untreated patients was validated in the TRANSBIG study .…”