10 years follow up of the RASTER study: implementing a genomic signature in daily practice

Background: In 2004 the 70-gene signature, MammaPrint® (MP), developed to predict High or Low Risk of distant breast cancer (BC) recurrence, was introduced in the observational RASTER trial. Patients (cT1–3N0M0) and their doctors took the clinical Dutch guideline and MP in to account to decide on adjuvant systemic treatment (AST). Five years follow-up data confirmed the prognostic value of the MP (Drukker, Int J Cancer, 2013). In this analysis we report the outcome at 10 years. Methods: Ten year survival data was available for all 427 Raster patients, age < 61. For the current analysis, clinical high (C-high) or low (C-low) risk was scored according to the modified version of Adjuvant! Online (Cardoso, N Engl J Med, 2016). 10-year distant-recurrence-free-interval (DRFI) probabilities were compared between risk groups based on the 70-gene signature and clinical assessment. Results: The 70-gene signature identified 51.4% (219/427) patients with a genomic Low Risk of BC recurrence (G-low). 10-year DRFI in patients with G-low or genomic High Risk (G-high) was 93.7% and 86.8% respectively (HR 1.4; 95% confidence interval{CI] 1.0-1.9). Clinical assessment identified 57% as C-low. The 10-year DRFI was 91.7% in C-low and 88.2% in C-high (HR 1.4; 95%CI 0.8-2.6). The 10-year DRFI in the combined genomic and clinical riskgroups was 94.4% in patients with a C-low/G-Low profile, only 11.6% of them received AST. In the C-low/G-High group 10-years DRFI was 88.5%, over 90% of them received AST. For C-high risk patients 10-year DRFI was 90.9% if G-Low (n = 46) and 87.3% if G-High (n = 137). In ER-positive BC (ER+) (N = 342) 10-years DRFI was 93.6% (G-Low) versus 88.8% (G-High) (HR 1.6; 95%CI 0.8-3.3). With clinical risk assessment, 10-years DRFI in ER+ was 91.6% (C-low) versus 91.9% (C-high). Conclusions: Patients who omitted chemotherapy based on MammaPrint Low Risk had an excellent 10 year DRFI, confirming the prognostic value of the MP. When C-high, the MP identified another 10.8% (46/426) of patients as G-Low who might forego adjuvant chemotherapy if ER+. In contrast to genomic risk stratification, the clinical risk assessment was unable to differentiate for survival between ER+ C-high and C-low risk patients