Tumor Flare-Like Response: A Novel Imaging Phenomenon with Predictive Significance in Triple Negative Breast Cancer Patients Undergoing Neoadjuvant Immuno-Chemotherapy

BACKGROUND:Preoperative immuno-chemotherapy improves outcomes in triple-negative breast cancer, but associated imaging response patterns remain poorly characterized. This study aimed to describe a novel MRI phenomenon, tumor flare-like response (TFLR), and evaluate its association with pathological complete response (pCR). METHODS:Ad hoc imaging analysis of a prospective phase II trial (NCT04213898; n = 39). Breast MRI was performed at baseline and after every two cycles. TFLR was defined a priori as new enhancing nodules (≥5 mm) separate from the index tumor on DCE-MRI, appearing during neoadjuvant therapy with subsequent regression. Inter-reader agreement was assessed with Cohen's kappa and intraclass correlation coefficient. Univariate logistic regression and ROC analysis (Youden index) with 1000-bootstrap resampling identified the optimal largest-nodule size cut-off for pCR prediction. Two multivariable logistic regression models (continuous-size and binary-size) evaluated independence after adjustment for PD-L1 status, FGT category, baseline tumor size, and clinical stage; multicollinearity was assessed by variance inflation factor. RESULTS:TFLR occurred in 74.4% (29/39) of patients and was significantly associated with higher FGT density (P = .03). Among the 29 patients with TFLR, nodules were predominantly oval (93.1%) with circumscribed margins, homogeneous enhancement. Distribution was bilateral (72.5%), ipsilateral (17.2%), or contralateral (10.3%) relative to the primary tumor, with consistently asymmetric counts between breasts. Kinetic curves were persistent (31.0%), plateau (27.6%), or washout (41.4%). TFLR first appeared after cycle 2 in all cases and completely resolved in 75.9% (22/29) by treatment completion; median persistence was 152 days (95% CI 145-159). Presence of TFLR alone did not predict pCR (P = .72). Patients with largest nodule ≥9 mm had significantly higher pCR rate (77.8% vs. 36.4%, P = .048). ROC analysis identified 9 mm as the optimal cut-off. In multivariable analysis, largest nodule diameter remained independently predictive whether analyzed continuously (OR = 2.965, 95% CI 1.298-6.772, P = .01) or dichotomized at ≥9 mm (OR = 7.833, 95% CI 1.260-48.701, P = .027). Model AUCs were 0.904 (95% CI 0.797-1.00) and 0.727 (95% CI 0.519-0.936), respectively. CONCLUSIONS:TFLR is a frequent, reversible MRI finding in TNBC treated with camrelizumab-based neoadjuvant immuno-chemotherapy. Largest nodule diameter ≥9 mm is a strong, independent predictor of pathological complete response and represents a promising early, non-invasive imaging biomarker of immunotherapeutic efficacy.