HER2 (2+)/SISH-positive vs. HER2 (3+) Breast Cancer: Pre-treatment MRI Differences and Accuracy of pCR Prediction on Post-treatment MRI

Rationale and Objectives: To evaluate whether HER2 (human epidermal growth factor receptor 2) (2+)/SISH (silver-enhanced in situ hybridization)+ and HER2 (3+) breast cancers exhibit distinct imaging characteristics on pre-treatment MRI and assess differences in pCR (pathologic complete response) prediction accuracy on post-treatment MRI, considering interobserver variability. Methods: This retrospective study included 301 HER2-positive breast cancer patients (mean age, 54 ± 10 years) who underwent NAC and surgery. Pre-treatment MRI features were analyzed in consensus. Two radiologists independently assessed post-treatment MRI for shrinkage patterns and response according to RECIST v1.1, further categorizing complete responses into rCR (radiologic complete response) and near-rCR. Interobserver agreement was measured (Cohen's kappa), and pCR was defined as no residual invasive or in situ tumor in the breast (ypT0) on the final pathology report. Sensitivity, specificity, and AUC were used to evaluate pCR prediction. Results: Fifty-four patients had HER2 (2+)/SISH+ and 247 had HER2 (3+) tumors. pCR rates were significantly higher in HER2 (3+) (58.7% vs. 18.5%, p < 0.001). On pre-treatment MRI, HER2 (2+)/SISH+ tumors more often appeared as single masses, while HER2 (3+) tumors showed more NME (non-mass enhancement) (44.5% vs. 16.7%, p < 0.001) and mass with NME (33.6% vs. 9.3%, p = 0.005). Post-treatment MRI showed simple concentric shrinkage in HER2 (2+)/SISH+ and no enhancement in HER2 (3+). Agreement was moderate (κ = 0.541–0.588). For pCR prediction, rCR alone yielded AUCs ranging from 0.659 to 0.756. Adding near-rCR improved specificity but reduced sensitivity, with a significant AUC increase for one reader (p = 0.011). Conclusion: Pre-treatment MRI revealed distinct imaging characteristics between subgroups. While pCR rates were higher in HER2 (3+), MRI-based pCR prediction showed similar performance, though near-rCR reduced sensitivity.