Ten-year clinical outcomes in N0 ER+ breast cancer patients with Recurrence Score-guided therapy

Beatrice Uziely,Daniela Katz,Ora Rosengarten,Georgeta Fried,Bella Nisenbaum,Julie Baron,Margarita Tokar,Mariana Steiner,Debbie M Jakubowski,Nicky Liebermann,Shulamith Rizel,Avital Bareket-Samish,Salomon M Stemmer,Michelle Leviov,Amit Itay,Steven Shak,Lior Soussan-Gutman,Noa Ben-Baruch,David B Geffen

doi:10.1038/s41523-019-0137-3

Abstract

The 21-gene Recurrence Score (RS) assay is a validated prognosticator/predictor of chemotherapy (CT) benefit in early-stage estrogen receptor (ER)-positive breast cancer (BC). Long-term data from real-life clinical practice where treatment was guided by the RS result are lacking. We performed exploratory analysis of the Clalit Health Services (CHS) registry, which included all CHS patients with node-negative ER+ HER2-negative BC who underwent RS testing between 1/2006 and 12/2009 to determine 10-year Kaplan–Meier estimates for distant recurrence/BC-specific mortality (BCSM) in this cohort. The analysis included 1365 patients. Distribution of RS results: RS 0–10, 17.8%; RS 11–25, 62.5%; RS 26–100, 19.7%. Corresponding CT use: 0, 9.4, and 69.9%. Ten-year distant recurrence rates in patients with RS 0–10, 11–25, and 26–100: 2.6% (95% confidence interval [CI], 1.1–6.2%), 6.1% (95% CI, 4.4–8.6%), and 13.1% (95% CI, 9.4–18.3%), respectively (P < 0.001); corresponding BCSM rates: 0.7% (95% CI 0.1–5.1%), 2.2% (95% CI, 1.3–3.7%), and 9.5% (95% CI, 6.0–14.9%) (P < 0.001). When the analysis included patients treated with endocrine therapy alone (95.5/87.5% of patients with RS 0–10/11–25), 10-year distant recurrence and BCSM rates for RS 0–10 patients were 2.7% (95% CI, 1.1–6.5%) and 0.8% (95% CI, 0.1–5.3%), respectively, and for RS 11–25 patients, 5.7% (95% CI, 3.9–8.3%) and 2.0% (95% CI, 1.1–3.7%), respectively. For RS 11–25 patients, no statistically significant differences were observed in 10-year distant recurrence/BCSM rates between CT-treated and untreated patients; however, this should be interpreted cautiously since the number of events was low and patients were not randomized. In conclusion, in node-negative ER+ HER2-negative BC patients, where treatment decisions in real-life clinical practice incorporated the RS, patients with RS 0–25 (~80% of patients, <10% CT use) had excellent outcomes at 10 years. Patients with RS 26–100 had high distant recurrence risk despite CT use and are candidates for new treatment approaches.

Highlights

The 21-gene Oncotype DX Breast Recurrence Score® assay is a validated prognostic/predictive tool used to guide adjuvant treatment decisions in estrogen receptor (ER)+ HER2-negative early breast cancer (BC).[1,2,3,4,5,6,7] The initial validation used a prospective–retrospective design
The hazard ratio (HR) for ≥2 vs
Long-term clinical outcomes were very good in RS 0–25 patients who received endocrine therapy (ET) alone

Summary

Introduction

The 21-gene Oncotype DX Breast Recurrence Score® assay is a validated prognostic/predictive tool used to guide adjuvant treatment decisions in estrogen receptor (ER)+ HER2-negative early breast cancer (BC).[1,2,3,4,5,6,7] The initial validation used a prospective–retrospective design. PlanB), as well as with analyses of the SEER registry and the National Cancer Data Base.[4,5,6,7,8]. We have previously reported an analysis of the CHS registry focusing on treatment decisions/. Clinical outcomes in RS-tested node-negative BC patients whose treatment decisions in clinical practice incorporated the RS results.[9] Our analyses of 1801 patients with ~6 years of median follow-up demonstrated that 5-year clinical outcomes (risk of distant recurrence, breast cancer-specific mortality [BCSM]) were consistent with the RS validation studies further confirming its clinical utility. Our findings supported the use of endocrine therapy (ET) alone in node-negative patients with RS 0–25.9

Methods

Results

Conclusion