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

Baha Sharaf,1 Alaa Seif,2 Hira Bani Hani,1 Maha Alhasan,1 Rnad Khader,1 Maram Al-Yag’oub,1 Ameed Ghanem,1 Jinan Bani Ata,1 Batool Ajlouni,1 Qutaiba Jawarneh,1 Adel Jaffal,1 Faris Tamimi,1 Sharif Jehad,3 Haneen Al-Abdallat,4 Osama Mahafdah,1 Hikmat Abdel-razeq1,4 1Internal Medicine Department, King Hussein Cancer Center, Amman, Jordan; 2Surgical Department, King Hussein Cancer Center, Amman, Jordan; 3School of Medicine, Yarmouk University, Irbid, Jordan; 4School of Medicine, The University of Jordan, Amman, JordanCorrespondence: Hikmat Abdel-razeq, Department of Internal Medicine, King Hussein Cancer Center, 202 Queen Rania Al Abdullah Street P.O. Box: 1269, Amman, 11941, Jordan, Tel +962-6 5300460, Ext: 1000, Email [email protected]: 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.Keywords: TCHP, HER2-positive breast cancer, neoadjuvant therapy, pCR, real-world evidence