Evaluation of the Immunohistochemical and Molecular Characteristics of Breast Cancers Exhibiting Fibrotic Scar Formation Following Neoadjuvant Chemotherapy

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Objectives: Neoadjuvant chemotherapy (NACT) is widely used in breast cancer to reduce tumor burden and enable breast-conserving surgery.While pathological complete response is commonly used to assess efficacy, residual disease often shows heterogeneous morphological and biological patterns.Understanding this heterogeneity, particularly within fibrotic scar-dominant tumor beds, can provide insights into tumor biology, guide surgical planning, and optimize pathological sampling.This study aimed to examine the relationship between residual tumor distribution patterns and hormone receptor expression and discuss the clinical implications. Material and Methods:We retrospectively analyzed 113 patients who underwent surgery following NACT between 2019 and 2025.Residual disease within the tumor bed was classified as either confined to the fibrotic scar or dispersed across a broader area.Immunohistochemical analyses included estrogen receptor (ER) and progesterone receptor (PR) expression.Morphological features were correlated with clinical and radiological findings, and ROC curves assessed the predictive capacity of receptor expression for residual patterns.Results: In 87.6% of cases, residual tumor was confined within the fibrotic scar, while 12.4% exhibited a dispersed pattern.ER and PR expression levels were significantly higher in cases with a dispersed residual pattern (ER AUC=0.718;PR AUC=0.736),suggesting an association with hormone receptor-positive tumors.Ki-67 proliferation index did not differ significantly between patterns, indicating that proliferation alone does not explain the morphological spectrum.Clinically, dispersed patterns increased the risk of underestimating residual disease on imaging, highlighting the importance of comprehensive tumor bed evaluation. Conclusion:These findings indicate that NACT response is not a uniform biological process and that residual tumor distribution may correlate with hormone receptor expression.The morphological and biological heterogeneity of residual disease is essential for guiding surgical planning and pathological sampling.In cases with likely dispersed patterns, ensuring margin safety and intensifying sampling may improve assessment of true residual extent.Recognizing these patterns can help anticipate discrepancies between imaging and actual disease, improve interpretation of treatment response, and support more personalized, biology-driven post-NACT management.

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