Residual Microcalcifications After Neoadjuvant Chemotherapy: Implications for Surgical Decision-Making—A Systematic Review

<b>Background</b>: The clinical and oncologic significance of residual microcalcifications after neoadjuvant chemotherapy (NAC) in breast cancer remains poorly defined. While traditionally regarded as radiologic indicators of residual malignancy warranting complete surgical excision, accumulating evidence suggests that many post-treatment calcifications represent benign or in situ changes with limited prognostic relevance. This systematic review synthesizes current evidence to clarify the diagnostic, pathologic, and oncologic implications of persistent calcifications after NAC. <b>Methods</b>: Following PRISMA 2020 guidelines, we conducted a comprehensive search of PubMed, Embase, the Cochrane Library, Scopus, and Google Scholar for studies published between January 2000 and May 2025. Eligible studies included adult breast cancer patients treated with NAC who demonstrated residual calcifications on mammography or MRI with corresponding histopathologic or survival data. Two reviewers independently performed study selection, data extraction, and quality assessment using the Newcastle-Ottawa Scale and AMSTAR-2. <b>Results</b>: Twenty-four studies involving over 3000 patients were included. Across cohorts, 35-55% of residual calcifications were benign, and many others corresponded to ductal carcinoma in situ rather than invasive carcinoma. Calcifications frequently persisted despite pathologic complete response (pCR), particularly in HER2-positive and triple-negative subtypes. MRI demonstrated superior concordance with pathology compared with mammography. Persistent calcifications did not consistently correlate with worse disease-free or overall survival when pCR was achieved. Radiologic-pathologic discordance contributed to overtreatment in some cohorts, including unnecessary mastectomy or extensive resections. <b>Conclusions</b>: Residual calcifications after NAC should not be regarded as a definitive surrogate of residual invasive disease nor as an obligatory indication for complete surgical removal. Their frequent benign or in situ pathology and limited prognostic value support a more individualized approach to surgical planning, prioritizing pathologic response and margin status over radiographic calcifications alone.