Abstract
Purpose: Both 12 and 6 months of trastuzumab in combination with chemotherapy are effective for HER2+ early-stage breast cancer. This meta-analysis was performed to assess the effectiveness and the toxicity of the two durations.Methods and Materials: We acquired relevant randomized controlled trials (RCTs) from PubMed, the Cochrane Library, ScienceDirect, EMBASE, Ovid MEDLINE, Web of Science, Scopus, and Google Scholar. Our endpoints included disease-free survival (DFS), overall survival (OS), number of recurrences, mortality and early stopping of trastuzumab, and adverse events (AEs).Results: We included five good-quality studies. Both durations of trastuzumab were effective among women with HER2+ early-stage breast cancer, but 12 months of trastuzumab appeared to have better DFS [hazard ratio (HR) = 1.10, 95% confidence interval (CI): 0.99–1.23, P = 0.09] and better OS than 6 months of trastuzumab (HR = 1.14, 95% CI: 0.99–1.32, P = 0.07). However, the 12 month group had more AEs, especially cardiac events [risk ratio (RR) = 0.66, 95% CI: 0.56–0.77, P < 0.00001]. In our sub-analyses, the 12 months duration had better DFS among patients using trastuzumab concurrently than the 6 months duration (HR = 1.23, 95% CI: 1.06–1.44, P = 0.006). Additionally, the 12 months duration had superior OS in women with ER-negative breast cancer (HR = 1.51, 95% CI: 1.10–2.08, P = 0.01) and patients treated with trastuzumab concurrently than the 6 months duration (HR = 1.61, 95% CI: 1.13–2.29, P = 0.008).Conclusions: Twelve months was the standard duration of adjuvant trastuzumab among patients with HER2+ early-stage breast cancer, with a tendency toward superior survival. However, patients in the 12 month group had more significant cardiac toxicity than those in the 6 month group.
Highlights
Human epidermal growth factor receptor 2 (HER2) is overexpressed or amplified in ∼15 to 20% of women with invasive breast carcinomas, which is associated with poor outcomes [1]
Articles that followed the PICOS (Participants, Intervention, Control, Outcomes, Study design) selection criteria were eligible—(1) participants: women aged ≥18 years histologically diagnosed with HER2+ early-stage breast cancer in accordance with the American Society of Clinical Oncology (ASCO) guidelines [17]; [2] intervention and control: 6 months vs. 12 months of adjuvant trastuzumab; [3] outcomes: disease-free survival (DFS) [defined as the date from randomization to the date of first recurrence, the occurrence of contralateral breast cancer, the occurrence of a second non-breast primary malignancy, or death], overall survival (OS), the number of patients who relapsed, died, and stopped trastuzumab early, and adverse events (AEs); and [4] study design: randomized controlled trials (RCTs) published in English
The pooled results found that the 12 month group had superior DFS among breast cancer patients treated with trastuzumab concurrently (HR = 1.23, 95% confidence intervals (CIs): 1.06–1.44, P = 0.006)
Summary
Human epidermal growth factor receptor 2 (HER2) is overexpressed or amplified in ∼15 to 20% of women with invasive breast carcinomas, which is associated with poor outcomes [1]. 1 year of trastuzumab has been commonly used as the standard duration in patients with HER2+ early-stage breast cancer [9, 10]. To reduce the toxicity and costs for women with HER2+ breast cancer, many randomized controlled trials (RCTs) have investigated different durations of trastuzumab [11,12,13,14,15,16]. These clinical trials reported inconsistent results for different durations vs 12 months of trastuzumab. In a prospective, phase-III RCT of 152 centers, Earl et al indicated that 6 months of trastuzumab therapy showed non-inferiority to 1-year therapy [4-year disease-free survival (DFS): 6 month group, 89.38%; 12 month group, 89.78%], with fewer cardiac events and fewer cases of serious toxicity in the 6 month group than in the 12 month group [16]
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