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The REMINAC Study: rethinking surgical implications for REsidual MIcrocalcifications after NeoAdjuvant chemotherapy
Sabatino D'Archi1, Beatrice Carnassale1, Lorenzo Scardina1
1Breast Surgery Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Introduction:
Persistent mammographic microcalcifications after neoadjuvant chemotherapy (NAC) remain a frequent driver of surgical extent in breast cancer, although their pathological significance is heterogeneous. This study assessed the radiologic-pathologic relationship between residual microcalcifications and residual disease after NAC and its surgical implications.
Materials And Methods:
We retrospectively analyzed 495 patients with invasive breast cancer treated with NAC and surgery between 2016 and 2024 who had mammographic microcalcifications at baseline. Post-NAC mammography (MG) and magnetic resonance imaging (MRI) were compared with final pathology. The primary endpoint was the estimated benign fraction within the post-NAC microcalcification extent, calculated as a linear proxy. Secondary endpoints included subtype-specific radiologic-pathologic correlations and post-hoc signals of potential surgical overtreatment among mastectomy patients.
Results:
Persistent microcalcifications were observed in 478/495 patients (96.6%). The estimated benign fraction was high (median 72.0%, IQR 13.8-100.0), exceeding 50% in 291/478 (60.9%) and 75% in 223/478 (46.7%). Benign fractions were highest in HER2-positive tumours and triple-negative breast cancer. MG showed weak correlation with pathological residual extent, whereas MRI showed stronger correlation but only moderate diagnostic discrimination (AUC 0.71, 95% CI 0.66-0.76), with a low NPV (40.8%). Among mastectomy patients, 49/239 (20.5%) had a calcification-only residual imaging pattern; 51.0% of these had ypT0 and 83.7% had residual disease ≤ ypT1a.
Conclusion:
Residual microcalcifications after NAC frequently overestimate pathological residual disease, especially in biologically responsive subtypes. Surgical escalation should not be driven by mammographic calcification extent alone, but should integrate tumour biology, multimodal imaging findings, pathological risk, and multidisciplinary assessment.