Post-Surgical Reassessment of Breast Cancer IHC: Concordance, Δ-Metrics, and Treatment-Relevant Reclassification

<b>Background/Objectives</b>: Immunohistochemical (IHC) profiles assessed on core biopsies guide initial therapy in breast cancer; however, paired changes between biopsy and surgical specimens may alter treatment pathways. We aimed to quantify paired biomarker dynamics (ER, PR, HER2, Ki-67) and the proportion of patients undergoing clinically actionable reclassification. <b>Methods</b>: We conducted a single-center retrospective study of 79 patients with paired pre- and post-surgical IHC for ER, PR, HER2 (0/1+/2+/3+ with reflex ISH for 2+), and Ki-67 (20% cut-off). Paired categorical shifts were tested with McNemar's test; agreement was quantified using Cohen's κ (95% CI); and multivariable logistic regression examined correlates of neoadjuvant chemotherapy (NACT). Two-sided <i>p</i> < 0.05 denoted statistical significance. <b>Results</b>: Post-surgical reassessment showed measurable conversions: PR-negative increased from 15.19% to 27.85%, while PR-positive decreased 84.81%→72.15%; HER2 3+ contracted 11.39%→6.33% with a parallel rise in 2+ (equivocal) 17.72%→24.05%; Ki-67 < 20% rose 37.97%→56.96%, whereas the >30% category was absent post-surgery. McNemar tests indicated significant paired shifts for PR (<i>p</i> = 0.016) and Ki-67 (<i>p</i> = 0.009); agreement was substantial for ER (κ = 0.70) and lower for PR (κ = 0.49), HER2 (κ = 0.43), and Ki-67 (κ = 0.29). High proliferation (Ki-67 ≥ 20%) independently predicted NACT (OR = 4.36, 95% CI 1.48-12.80). <b>Conclusions</b>: Paired IHC reassessment from biopsy to surgery reveals biomarker conversions that can reclassify therapeutic eligibility (e.g., anti-HER2 candidacy, endocrine strategies). These data support selective confirmation of IHC on resection specimens in routine practice and provide Δ-metrics to inform decision-making; external validation in prospective cohorts is warranted.