Post-NAC Microcalcifications in Breast Cancer: Rethinking Surgical Indications in the Era of Precision Oncology

Residual microcalcifications after neoadjuvant chemotherapy (NAC) in breast cancer remain a complex diagnostic and therapeutic challenge. Although NAC has significantly improved pathologic complete response (pCR) rates and transformed surgical approaches, the persistence or evolution of microcalcifications may not accurately reflect residual disease. This discrepancy complicates radiologic interpretation, impacts surgical decision-making, and may lead to overtreatment or unnecessary mastectomies. This review synthesizes current evidence on the radiologic–pathologic correlation of post-NAC microcalcifications, their prognostic value, and their relevance to guiding surgical management in contemporary precision oncology. A narrative review of the literature was performed, focusing on imaging evolution after NAC, pathologic correlations, predictive and prognostic implications, and the role of microcalcifications in defining optimal surgical strategies, ranging from breast-conserving surgery to mastectomy. Emerging contributions from digital breast tomosynthesis, contrast-enhanced mammography (CEM), Magnetic Resonance (MR) and radiomics are also examined. Studies consistently demonstrate that residual microcalcifications are often poor predictors of viable tumor tissue after NAC. Up to half of cases with persistent calcifications may reflect minimal or absent residual invasive cancer, whereas calcifications may also persist in areas of treatment-induced necrosis or fibrosis. Reliance on calcifications alone may therefore lead to unnecessary extensive resections. Conversely, specific morphologic patterns, especially fine pleomorphic or branching calcifications, are more strongly associated with residual malignancy. Advanced imaging and radiomics show promise in improving predictive accuracy. Residual microcalcifications after NAC should not be interpreted as a direct surrogate of residual disease. A multimodal assessment integrating imaging evolution, tumor biology, and treatment response is essential to optimize surgical planning and avoid overtreatment. Precision surgery in the NAC era increasingly requires individualized decision-making supported by advanced imaging and robust radiologic–pathologic correlation.