This research aimed to examine the neoadjuvant chemotherapy (NACTx) pathway in breast cancer (BC) patients, highlighting major therapy-related adverse effects (trAEs), tumor response profiles, operative and histopathologic outcomes, and determining the predictors of cavity shaving and axillary lymph node dissection (ALND) after sentinel lymph node biopsy (SLNB). A retrospective single-institution analysis was performed on individuals who received NACTx for BC between 2015 and 2021. Records from 242 cases were analyzed. Roughly 21.5% experienced grade ≥3 trAEs, and 3.3% discontinued therapy. Anthracycline-related cardiotoxicity occurred in 2.2%, including one fatality (mortality rate 0.4%). Surgical and pathological assessments were feasible for 229 participants. Clinical progression was reported in 3.9% (notably 14% among triple-negative BC; p = 0.004). Breast-conserving surgery (BCS) was achieved in 55% of patients. Surgical type (BCS vs. mastectomy) showed no meaningful relation with histologic classification, tumor size, molecular subtype, or pathological response level. Among BCS cases (n = 134), 20% needed cavity shaving because of invasive carcinoma at the surgical margin (SM). Both tumor histology (ductal vs. lobular; OR: 4.962, 95% CI 1.007–24.441, p = 0.049) and SUVMax score (OR: 0.866, 95% CI 0.755–0.993, p = 0.039) were independent determinants of SM involvement. SLNB was initially used in 75%, yet nearly half later required ALND. ALND incidence was higher in luminal A and LB-HER2(−) phenotypes (87% vs. 69%) compared with HER2(+) and triple-negative (43–50%) subgroups (p = 0.001). Every luminal A case and all invasive lobular tumors needed ALND after SLNB, whereas none in the HER2-enriched group did. Elevated ER and PR expressions increased the probability of requiring ALND, whereas HER2 positivity and higher lymph node SUVMax were inversely correlated. Overall, 27% reached complete pathological remission (pCR), though none occurred in luminal A patients. Owing to the risks of toxicity and disease advancement, the NACTx process requires vigilant clinical oversight. Treatment planning should be made by experienced multidisciplinary tumor boards that account for tumor biology and predicted therapeutic outcomes.
