Abstract P3-11-02: Breast cancer-specific mortality (BCSM) in patients (pts) with node-negative (N0) and node-positive (N+) breast cancer (BC) guided by the 21-gene assay: A SEER-genomic population-based study

Abstract

Introduction: The 21-gene Breast Recurrence Score® (RS) in the randomized NSABP B-20, SWOG S8814, and TAILORx studies predicted chemotherapy (CT) benefit for pts with N0 and N+ disease. Endocrine therapy was not inferior to chemoendocrine therapy in 6,711 randomized TAILORx pts with RS 11-25 and N0 disease. We characterized BCSM for the TAILORx-defined RS groups (0-10, 11-15, 16-20, 21-25, and 26-100) in the large population-based SEER study of pts treated based on RS results. Methods: RS results were provided electronically to SEER registries per their linkage methods (Petkov npj Breast Cancer 2016). Eligible pts were diagnosed Jan 2004 - Dec 2014 with N0 and N+(N1mic, 1-3 positive nodes[N1]), HR+, HER2-negative BC, and had no prior malignancy or multiple tumors, with follow-up information through Dec 2015. BCSM estimates by reported CT use yes vs. no/unknown were computed, and must be interpreted cautiously given lack of randomization. Results: There were 80,605 pts with RS results; 70,087 with N0 disease, 4,336 with N1mic, and 6,182 with N1. Median follow-up was 49 months, with 20,151 pts followed >76 months. 1,020 pts had experienced breast cancer death. There was a significant positive association between higher RS results and increased BCSM (p<0.001) without and with adjustment for nodal status, age, tumor size, and grade. Reported CT use increased with increasing RS result (Table). 9-y BCSM was <4% without CT for pts with RS 0-25 and N0 disease and for pts with RS 0-20 and N1 disease. For RS 26-100, 9-y BCSM was lower with CT use than without (Table). Similar results were seen in the 4,336 pts with N1mic disease. Pts treated with CT for every RS group, as expected, tended to have higher risk features (age, tumor size and grade), and multivariable models and adjustment by propensity scores will be presented to allow for more definitive conclusions. Table N0; CT Use No (N=55726)N0; CT Use Yes (N=14361)N1; CT Use No (N=3810)N1; CT Use Yes (N=2372)RS 0-10n139823891005283 9-y BCSM1.4% (1.0%, 2.1%)2.1% (0.7%, 5.9%)2.2% (1.0%, 4.8%)1.4% (0.4%, 4.6%)RS 11-15n1675810661193453 9-y BCSM2.0% (1.5%, 2.6%)2.7% (1.3%, 5.4%)1.5% (0.8%, 3.1%)4.4% (1.4%, 13.6%)RS 16-20n144842719992587 9-y BCSM2.2% (1.7%, 2.8%)1.9% (1.1%, 3.0%)3.8% (1.6%, 8.5%)4.2% (1.6%, 10.9%)RS 21-25n67043544397431 9-y BCSM3.9% (3.0%, 5.0%)3.4% (2.6%, 4.6%)7.1% (4.1%, 12.1%)5.7% (2.9%, 11.2%)RS 26-100n37986643223618 9-y BCSM8.8% (7.4%, 10.4%)7.0% (5.9%, 8.4%)15.2% (8.7%, 25.9%)10.8% (7.2%, 16.2%) Conclusion: In both N0 and N+ disease (up to 3 positive nodes), low RS results identify more than 70% of BC patients with excellent long-term outcomes and no apparent CT benefit, and high RS results (26-100) identifies an important minority of patients where CT reduces BCSM. Real-world evidence from SEER reconfirms that the 21-gene assay is prognostic and strongly suggests it is predictive of CT benefit, irrespective of nodal status. Citation Format: Hortobagyi GN, Shak S, Sledge, Jr. GW, Winer EP, Albain KS, Mamounas EP, Jakubowski DM, Petkov VI, Wolmark N. Breast cancer-specific mortality (BCSM) in patients (pts) with node-negative (N0) and node-positive (N+) breast cancer (BC) guided by the 21-gene assay: A SEER-genomic population-based study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-11-02.

Impact of 21-Gene Breast Cancer Assay on Treatment Decision for Patients with T1–T3, N0–N1, Estrogen Receptor-Positive/Human Epidermal Growth Receptor 2-Negative Breast Cancer: Final Results of the Prospective Multicenter ROXANE Study

“…The 9‐year breast cancer‐specific survival rates were 98.2% for RS ≤11, 99% for RS 11–15, 96.7% for RS 16–20, 93.1% for RS 21–25, and 84.2% for RS ≥26. Despite that the magnitude of the benefit of CT is uncertain in N1 patients as a result of the low number of events, the observed difference in breast cancer‐specific survival with CT in N1 patients was <1% at both 5 years and 9 years . Therefore, while waiting for the data of the large RxPONDER randomized trial, available evidence supports the potential utility of the RS test in N1 patients.…”

Multigene assays in early breast cancer: Insights from recent phase 3 studies

“…As a result, there is no purely prospective evidence that confirms a benefit, or lack thereof, for patients with RS 26-30. Notwithstanding that pure-prospective data gap, a recently published analysis of the NSABP B-20 study, excluding patients with HER2- Table 5 Clinical outcomes in patients 50 years old in the randomized arms (RS [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] in TAILORx (ITT population) [6].…”

“…This study was sized with power to determine whether adjuvant ET alone would be inferior to a CT-containing adjuvant treatment in a mid-risk patient population [5,6]. For TAILORx, the RS midrange cutpoints used (RS [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] were modified from those of the original validation studies [10e14]. This reflected a desire to avoid undertreatment of elevated-risk patients and to avoid missing a benefit of CT in individuals with lower-risk disease [5,6,10e14].…”

Routine Use of Oncotype DX Recurrence Score Testing in Node-Positive Hormone Receptor-Positive HER2-Negative Breast Cancer: The Time Has Come

“…Consideration for incorporating RS testing into staging for ER?, HER2-, node-positive breast cancer is further supported by work presented by Hortobagyi and colleagues at the 2018 San Antonio Breast Cancer Symposium (SABCS). 7 That study utilized the SEER database to establish BCSS in patients with ER?, HER2-, N0, N1mic, and N1 disease in whom RS data were available. They identified 80,605 patients treated from 2004 to 2014, including 70,087 who were N0, 4335 N1mic, and 6182 N1.…”

“…nodes. 7 There are caveats to both studies, including possible selection bias. These data include patients in whom the treating physician elected to send the RS from 2004 to 2014.…”