e13021 Background: Concurrent anti-HER2 therapies and chemotherapy improve response rates (43%-55% in prior studies). However, combined cardiotoxicity with anthracyclines has prompted the use of anthracycline-free regimens. This study compares the efficacy and safety of anthracycline-containing versus anthracycline-free (TCHP) neoadjuvant chemotherapy in HER2-positive early-stage breast cancer. Methods: This multicenter retrospective study analyzed HER2-positive breast cancer patients (2015–2025) treated with neoadjuvant anti-HER2 therapy and surgery. Clinicopathological, treatment, and outcome data were reviewed. Associations between regimens and pathological complete response (pCR; no residual invasive tumor in breast/axilla) and event-free survival (EFS; time to progression, recurrence, or death) were evaluated. Results: Of 358 patients (mean age 50), most had invasive ductal carcinoma, T2 tumors (74%), and N1 disease (60.9%). Common regimens were AC+DPT (35.2%) and TCHP (30.7%); 95.5% completed treatment. pCR rates were comparable between AC+DPT and TCHP (p = 0.360) but significantly lower with other regimens (OR 0.35, 95% CI 0.17–0.73; p = 0.005). HER2 3+ status and N3 involvement (HR 8.43, p = 0.038) predicted worse EFS; ER/PR status had no impact. Febrile neutropenia occurred in 8.2% (TCHP) vs. 1.6% (AC+DPT). No grade 3–4 cardiac toxicity occurred (Table 1). Conclusions: TCHP showed comparable efficacy to anthracycline-containing regimens with similar cardiac safety but higher hematological toxicity. Anthracycline-free regimens may be preferred for patients with cardiac risks. Advanced lymph node involvement remains a poor prognostic factor. Results of univariate and multivariate analyses of parameters affecting event-free survival. Univariate analysis Multivariate analysis Variables P value HR 95% CI P value HR 95% CI Grade Grade 1* 0.81 Grade 2 0.58 0.67 0.15-2.83 Grade 3 0.52 0.6 0.13-2.80 ER % (linear) 0.02 0.99 0.98-0.99 0.083 0.994 0.986-1.001 PR % (linear) 0.63 0.99 0.99-1.00 HER-2 status (+2*/+3) 0.02 9.03 1.24-65.3 0.038 8.436 1.12-63.43 Pathological subtype İDC* 0.65 İLC 0.97 <jats:td colspan="1" ro
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