Abstract P1-07-14: Real-life analysis evaluating &gt;1000 N0/N1mi estrogen receptor (ER)+ breast cancer patients for whom treatment decisions incorporated the 21-gene recurrence score (RS) result: Clinical outcomes with median follow up of &gt; 9 years
Authors: Stemmer SM , Rizel S , Steiner M , Geffen DB , Soussan-Gutman L , Bareket-Samish A , McCullough D , Svedman C , Nisenbaum B , Ryvo L , Peretz T , Fried G , Rosengarten O , Liebermann N , Ben Baruch N 
Published: February 2018

Abstract
Background: The 21-gene Recurrence Score (RS) Assay (Oncotype DX®) is a validated prognosticator and predictive of chemotherapy (CT) benefit in patients with hormone receptor (HR)+ human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In Israel, the RS assay has been reimbursed by Clalit Health Services (CHS, the largest HMO in Israel) since 2006, and the assay is widely used in eligible estrogen receptor (ER)+ patients. Notably, ER+ breast cancer patients have a protracted risk of recurrence with approximately half of all distant recurrences occurring after 5 years from diagnosis. The goal of the current ongoing analysis was to investigate early (≤5 years) and late (&gt;5 years) distant recurrence in N0/N1mi ER+ HER2-negative breast cancer patients who were RS-tested through CHS.
Methods: This analysis of the CHS registry included breast cancer patients with ER+ HER2-negative N0/N1mi disease who underwent RS testing from 1/2006 (CHS approval of the assay) through 1/2009. Data sources included CHS claims arms (for patient/tumor characteristics), Teva Pharmaceuticals (for tumor characteristics, RS result), and medical records (for treatment/recurrence/survival). The study was approved by the institutional review boards of the CHS Community Division and was granted a waiver for obtaining patient consent.
Results: The analysis included 1026 patients with median (interquartile range) follow up of 9.3 (8.8-10.2) years. Most patients were females (99%). Median (range) age was 59 (25-84) years; 92% had N0 and 8% had N1mi disease; 14%, 52%, and 16% had grade 1, 2, and 3 tumors, respectively (grade information was not available for 18% of patients); median (range) tumor size was 1.5 (0.3-6.5) cm. The majority of patients (78%) had invasive ductal carcinoma and 12% had invasive lobular carcinoma. Overall, 489 patients (48%) had RS&lt;18, 434 (42%) had RS 18-30, and 103 (10%) had RS≥31. The use of adjuvant CT was consistent with the RS result: 3%, 27%, and 90% of RS&lt;18, RS 18-30, and RS≥31 patients, respectively. Overall, 25 distant recurrences were reported within 5 years of RS testing: 5 (1.0%) in RS&lt;18 patients, 9 (2.1%) in RS 18-30 patients, and 11 (10.6%) in RS≥31 patients. In the first 5 years, breast cancer-specific death was reported in 8 patients including 3 (0.7%) with RS 18-30 and 5 (4.9%) with RS≥31 results. Among N0 patients with RS 11-25 who did not receive adjuvant CT (n = 540), 5 (0.9%) distant recurrences and one (0.2%) breast cancer death were reported within 5 years of RS testing. Analysis of 'late' recurrences and breast cancer-specific death (from 5 to 9.3 years of follow-up) is ongoing.
Conclusions: These will be the first late recurrence data from over 1000 patients for whom the RS result was used in real-life clinical decision making. Consistent with previous analyses of the CHS registry, CT use was appropriately based on the RS result, and the recurrence/survival outcomes (for the first 5 years) demonstrated the prognostic performance of the RS. Distant recurrence and breast cancer death data beyond 5 years will be presented at the meeting.
Citation Format: Stemmer SM, Rizel S, Steiner M, Geffen DB, Soussan-Gutman L, Bareket-Samish A, McCullough D, Svedman C, Nisenbaum B, Ryvo L, Peretz T, Fried G, Rosengarten O, Liebermann N, Ben Baruch N. Real-life analysis evaluating &gt;1000 N0/N1mi estrogen receptor (ER)+ breast cancer patients for whom treatment decisions incorporated the 21-gene recurrence score (RS) result: Clinical outcomes with median follow up of &gt; 9 years [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-14.