70-gene signature MammaPrint for early-stage HR-positive, HER2-negative breast cancer: Outcome in the MINDACT trial for key clinical-pathological high-risk subgroups.

BACKGROUND: Adjuvant chemotherapy (ACT) can be safely omitted in patients above 50 years of age with stage I-II hormone receptor positive (HR+) HER2-negative (HER2-) breast cancer and a low-risk 70-gene signature (MammaPrint®). However, the contribution of the 70-gene signature in high-risk subgroups by nodal involvement, grade 3 or larger tumors, has not been reported, which may complicate clinical decision making for these patients. PATIENTS AND METHODS: Patients above 50 years enrolled in the MINDACT trial with primary stage I-II HR + HER2- breast cancer and a clinical high/genomic low-risk were selected for this exploratory analysis. In the MINDACT trial, these patients were randomized at enrollment based on their risk assessment method for the decision to receive ACT or not. Eight-year distant metastasis free survival (DMFS) was the primary endpoint. RESULTS: Median follow-up was 8.7 years. Of the 868 clinical high/genomic low-risk MINDACT patients, 490 (56.5%) patients had tumors larger than 2 cm, 232 (26.7%) had grade 3 tumors and 406 (46.8%) had 1-3 involved lymph nodes. 8-year DMFS in the no ACT group was 87.9% (95%CI: 82.9-91.6%) in patients with tumors larger than 2 cm; 91.3% (95%CI: 84.0-95.4%) with grade 3 tumors and 89.6% (95%CI: 84.2-93.3%) with nodal involvement. Absolute 8-year DMFS benefit for ACT versus no ACT was 1.2%; -2.2% and 0.7% respectively. CONCLUSIONS: This exploratory subgroup analysis of the MINDACT trial confirms the prognostic performance of the 70-gene signature in patients with high-risk features such as larger tumors, grade 3 tumors and 1-3 involved lymph nodes.