Comparative Evaluation of a 28-Gene versus 70-Gene Panel for Recurrence Risk Prediction in Early-Stage HR-Positive/HER2-Negative Breast Cancer in Chinese Women

Background : Multigene expression assays help guide adjuvant therapy decisions in early-stage hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer by predicting recurrence risk. While the 21-gene Oncotype DX and 70-gene MammaPrint tests, developed in Western populations, allow low-risk patients to safely avoid chemotherapy, their validity in Asian cohorts remains understudied. A 28-gene signature (RecurIndex), developed using Asian patient data, predicts distant and locoregional recurrence. This study compares the 28-gene RecurIndex with the 70-gene MammaPrint in Chinese women with early HR+/HER2- breast cancer. Patients and methods : We retrospectively analyzed 99 Chinese patients (median age 52 years) with stage pT1-3N0-1 HR+/HER2- breast cancer who underwent MammaPrint testing post-surgery (2019-2022). Formalin-fixed paraffin-embedded tumor samples were retested using the 28-gene RecurIndex. Clinical-pathological risk was defined as ≥2 high-risk factors (age ≤40 years, tumor ≥T2, N1 nodal status, lymphovascular invasion, grade 3, Ki-67 ≥20%). Genomic risk stratification (high vs low) by each assay and concordance with clinical risk were assessed using Cohen’s kappa. Median follow-up was 56 months. Results : By clinical criteria, 48.5% (48/99) of patients were high-risk. The 28-gene assay classified 26% as high genomic risk versus 34% by the 70-gene MammaPrint. Overall concordance between assays was 72% (71/99 cases; kappa = 0.50). The 28-gene panel showed stronger alignment with clinical risk (kappa = 0.51) than the 70-gene (kappa = 0.39). Among clinically low-risk patients, 98% (50/51) were classified as low-risk by the 28-gene test compared to 84% (43/51) by the 70-gene. For clinically high-risk patients, both assays identified similar proportions as genomic high-risk (52% vs 54%, respectively). No recurrences or deaths occurred during follow-up. Conclusion : The 28-gene RecurIndex demonstrated comparable performance to the 70-gene MammaPrint in stratifying recurrence risk in Chinese HR+/HER2− breast cancer patients. It classified fewer patients as high-risk, identified a larger low-risk subgroup (74% vs 66%), and aligned more closely with traditional clinical-pathological factors. These findings support its potential as an ethnicity-tailored prognostic tool. Larger studies with extended follow-up are needed to confirm predictive accuracy and chemotherapy benefit in this population.