Abstract CT039: Primary analysis of the EORTC 10041/ BIG 3-04 MINDACT study: a prospective, randomized study evaluating the clinical utility of the 70-gene signature (MammaPrint) combined with common clinical-pathological criteria for selection of patients for adjuvant chemotherapy in breast cancer with 0 to 3 positive nodes

Background: The MINDACT TRIAL investigated the clinical utility of the 70-gene profile (MammaPrint®), when confronted to the standard clinical pathological (CP) criteria, for the selection of patients unlikely to benefit from adjuvant chemotherapy (CT).Methods: From 2007 to 2011, 11288 patients were screened in 112 centers from 9 countries, of whom 6693 were enrolled. Enrolled patients had undergone successful determination of their genomic risk G (with MammaPrint®) and clinical risk C (modified version Adjuvant! Online). Patients were evaluated as “low clinical risk”, if their 10-year disease specific survival (without CT or endocrine therapy (ET), as estimated by Adjuvant! Online, was greater than 88% for ER-positive patients, and greater than 92% for ER-negative patients. Patients characterized in both assessments as “low- risk” were spared CT while for those “high- risk”, CT was advised. Those with discordant results were randomized to use either C or G risk evaluation to decide on CT. The main hypothesis was that G-assay would outperform the C-criteria by reducing the administration of adjuvant CT without impairing outcome. The CT and ET regimen randomization will not be part of the current presentation. The primary endpoint for the CT (yes/no) decision was distant metastasis free survival (DMFS). Secondary endpoints were the proportion of women treated per C over G, the overall survival (OS) and disease free survival (DFS). In the G-low/C-high risk group, a null hypothesis of a 5-year DMFS of 92% was tested (one-sided a = 2.5%) in the patients who were randomized to use the 70-gene signature prognosis (no CT), and who complied with this “no CT” assignment. Results: Median age of enrolled patients was 55 years. Eighty percent were LN- negative. 58% had tumor size between 1 and 2cm, 88% were HR-positive and 10% were HER2 positive. The enrolled patients were categorized in 4 risk groups; G-low/C-low [2745 patients (41%)], G-high/C-low [592 (9%)], G-low/C-high [1550 (23%)] and G-high/C-high [1806 (27%)]. In the G-low/C-high group, 51% of patients were randomized to CT (49% to no CT) and in the G-high/C-low group 50% to CT. At 5- years, DMFS was 94.7% (95%CI, 92.5-96.2%) for patients who were C- high/ G- low and randomized to use G and received no CT. This CI exceeds 92%, thereby rejecting the primary null hypothesis of MINDACT. There was an absolute 14% reduction in adjuvant CT administration when using the G versus C treatment strategy. Conclusion: C-hi