Bridging Clinical Trials to Real-World Clinical Practice: TCHP Neoadjuvant Therapy Outcomes in HER2-Positive Breast Cancer.

Purpose: Trastuzumab-based neoadjuvant therapy (NAT) is standard for HER2-positive breast cancer (HER2+ BC). The TCHP regimen (docetaxel, carboplatin, trastuzumab, pertuzumab) demonstrated efficacy in clinical trials; however, real-world evidence remains limited. This study evaluates the effectiveness and safety of TCHP in routine clinical practice at King Hussein Cancer Center (KHCC). Patients and Methods: This retrospective study included 161 patients with HER2+ BC who received at least one cycle of TCHP between January 2022 and October 2024. The primary endpoint was pathological complete response (pCR; ypT0/is, ypN0). Secondary endpoints included safety, emergency room (ER) visits, and hospitalization rates. Logistic regression was used to identify predictors of pCR, reporting odds ratios (OR) and 95% confidence intervals (CI). Results: The cohort included 160 females and one male, with a median age of 51 years (24-80). Most patients were ER/PR-positive (73.9%), and 26.1% were ER/PR-negative. Tumors were predominantly high-grade (grade 3 in 106 patients), with nodal involvement in 95 patients. Surgical resection was performed in 143 patients. pCR was achieved in 45.5% of patients. HER2 IHC 3+ expression (adjusted OR 11.76; 95% CI 3.69-54.00; p<0.001) and ER/PR-negative status (adjusted OR 2.59; 95% CI 1.09-6.50; p=0.035) were independent predictors of pCR, while tumor stage and nodal status, were not. No cardiac toxicity or ejection fraction decline was observed. Anti-HER2 therapy was discontinued in six patients, and 11 did not complete six cycles. Chemotherapy dose reductions occurred in 38 patients, mainly due to hematologic toxicity. A median of three ER visits per patient was recorded, with hospitalization required in 42 patients, primarily for neutropenic fever and diarrhea. Conclusion: In this real‑world cohort, TCHP achieved a moderate pCR rate (45.5%), lower than clinical trial reports, with HER2 IHC 3+ and ER/PR‑negative status predicting response, but substantial toxicity-including frequent emergency visits and hospitalization, highlighting the need for improved patient selection, strengthened supportive care, and consideration of de‑escalation strategies to maintain efficacy while reducing morbidity.