Abstract Background: Chemotherapy dose intensity (DI), defined as the amount of drug given per unit of time, is a key determinant of efficacy in curable malignancies such as early-stage HER2-positive breast cancer. DI below 0.85 has been linked to worse survival outcomes and lower pathological complete response (pCR) rates. Factors contributing to reduced DI include myelosuppression, toxicities, drug shortages, and healthcare system barriers. This is among the first real-world studies to evaluate chemotherapy DI in early-stage HER2-positive breast cancer in a Middle Eastern population. Objective: This study aimed to evaluate the impact of chemotherapy dose intensity (DI) of the neoadjuvant TCHP regimen (docetaxel, carboplatin, trastuzumab, pertuzumab) on pathological complete response (pCR) rates in patients with early-stage HER2-positive breast cancer. A secondary objective was to identify patient- and system-related factors contributing to reduced DI, including the rate, frequency, and underlying causes of dose reductions and treatment delays. Methods: This retrospective cohort study included patients ≥18 years with stage I-III HER2-positive breast cancer treated with neoadjuvant TCHP at a tertiary center in Saudi Arabia from 2017 to 2023. Dose intensity (DI) was calculated as actual cumulative dose divided by intended dose ×100. The primary outcome was the association between DI and (pCR). Patients were stratified by DI (85% vs. ≥85%) and pCR status. Secondary outcomes included factors contributing to dose reductions and delays. Analyses included descriptive statistics and multivariable logistic regression. Results: A total of 149 patients were included. Most (73.2%) had nodal involvement; 59.7% were hormone receptor (HR) positive. The pCR rate was 60.4%. No significant differences in pCR were observed between DI groups for docetaxel (60% vs. 61%; p = 1.00) or carboplatin (65% vs. 56%; p = 0.35). Median DI was highest for trastuzumab (100%) and lowest for pertuzumab (72.2%). Protocol deviation to weekly paclitaxel occurred in 43.6% of patients. Carboplatin DI was independently associated with higher odds of pCR (OR 1.01; 95% CI, 1.00-1.04; p = 0.029), while HR positivity was associated with lower pCR odds (OR 0.23; 95% CI, 0.09-0.61; p = 0.004). Switching to paclitaxel showed a non-significant reduction in pCR (OR 0.26; 95% CI, 0.05-1.37; p = 0.107). Docetaxel had the highest delay rate, affecting up to 30% of patients, mainly due to rescheduling. Conclusion: In this real-world cohort, chemotherapy DI reductions were common. DI ≥0.85 was associated with numerically higher pCR, but only carboplatin DI independently predicted pCR. HR positivity and docetaxel substitution were linked to lower pCR odds. Docetaxel and pertuzumab experienced the most delays, mainly from system-related factors. These findings highlight the importance of adherence to protocol and timely delivery. Addressing modifiable system-level barriers and adhering to guideline-based chemotherapy are essential. Larger multicenter studies are warranted to confirm these findings. Citation Format: B. T. Albaqshi, S. K. AlHumiued, H. Abbas, A. Alamer, S. M. Alonaizi, R. A. Alyousef, F. R. Alqattan, A. Salam, F. A. Almulhim. Impact of Dose Intensity on Pathological Complete Response in Early-Stage HER2-Positive Breast Cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-13-10.
Albaqshi et al. (Tue,) studied this question.