Abstract
To compare outcomes in patients with human epidermal growth factor receptor-2 (HER2)-positive breast cancer who received either dose-dense neoadjuvant chemotherapy (NAC) with trastuzumab or standard-interval chemotherapy with trastuzumab. Patients with HER2-positive breast cancer who received NAC, including epirubicin and cyclophosphamide followed by paclitaxel with trastuzumab were included. Patients were divided into either the dose-dense or standard-interval group. We compared pathologic complete remission (pCR), distant disease-free survival (DDFS), event-free survival (EFS), and breast cancer-specific survival (BCSS) between the two groups. Two hundred (49.6%) patients received dose-dense NAC, and 203 (50.4%) received standard-interval NAC. The pCR rate was 38.4% in the dose-dense group and 29.2% in the standard-interval group (P = 0.052). In patients with lymph node (LN) metastases, the LN pCR rate was 70.9% in the dose-dense group and 56.5% in the standard-interval group (P = 0.037). After a median follow-up of 54.6 months, dose-dense chemotherapy presented an improvement on DDFS (hazard ratio [HR] = 0.49, 95% confidence interval [CI]: 0.19–1.28, EFS (HR = 0.54, 95% CI: 0.24–1.21), and BCSS (HR = 0.41, 95% CI: 0.11–1.51), but the difference was not significant. Compared with standard-interval chemotherapy, dose-dense chemotherapy resulted in a superior 5-year DDFS (100% vs. 75.3%, P = 0.017) and 5-year EFS (96.9% vs. 78.3%, P = 0.022) in patients younger than 40 years. HER2-positive patients can achieve a higher LN pCR rate with dose-dense NAC than with standard-interval NAC with trastuzumab. Better survival may also be achieved with dose-dense chemotherapy with trastuzumab than with standard-interval chemotherapy with trastuzumab among young patients (age ≤ 40 years).
Highlights
The Norton-Simon theory suggests that shortening the chemotherapy intervals but keeping the same dosage per cycle may increase the killing effect on tumor cells and reduce the regeneration between cycles[1,2]
We further investigated the effect of two chemotherapy regimens on the survival of patients with positive lymph node (LN), and they did not show significant improvement in distant disease-free survival (DDFS), event-free survival (EFS), and DDFS in the dosedense group compared with the standard-interval group (Table 4)
The present study showed that dose-dense chemotherapy significantly improved the pathologic complete remission (pCR) rate of LNs in patients with HER2-positive cancer who received trastuzumab, and improved DDFS and EFS among young patients
Summary
The Norton-Simon theory suggests that shortening the chemotherapy intervals but keeping the same dosage per cycle may increase the killing effect on tumor cells and reduce the regeneration between cycles[1,2]. The INT C9741 trial showed significant improvement in survival outcomes in the dose-dense treatment group compared with the standard-interval treatment group, which supported the Norton-Simon theory[3]. The above studies support the superior efficiency of dose-dense chemotherapy over standard-interval chemotherapy, and anti-HER2 therapy that has not been used for routine administration in most of the previous studies[3,5,6,7,8,9,10]. According to the retrospective results of the PANTHER trial and the GIM2 trial, it remains controversial whether dose-dense chemotherapy leads to superior survival compared with standard-interval chemotherapy with trastuzumab in HER2positive breast cancer[14,15]
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