Trastuzumab has been demonstrated to be an effective treatment in patients with human
epidermal growth factor receptor-2 (HER-2) positive
breast cancer (BC); however, inconsistent results with regards to the long-term survival benefits, safety and optimal administration timing of
trastuzumab exist. The present meta-analysis investigated these inconsistencies in patients with HER-2 positive BC that received adjuvant or neoadjuvant
trastuzumab. Computerized and manual searches were used to identify eligible randomized control trials (RCTs) to include in the analysis. Based on a fixed or random effects model, hazard and risk ratios were calculated and used to assess the survival advantages and risks of
trastuzumab. A total of 14,546 patients from 13 RCTs were included in the analysis; 9 RCTs used an adjuvant setting and 4 RCTs used a neoadjuvant setting. Analysis of RCTs with an adjuvant setting demonstrated that treatment with
trastuzumab and
chemotherapy in patients with HER-2 positive BC, in comparison with patients receiving
chemotherapy alone, improved disease-free survival, overall survival and overall response. However, a higher incidence of
neutropenia (P<0.0001),
leukopenia (P<0.0001),
diarrhea (P=0.002), skin/nail change (P=0.02), left ventricular ejection fraction reduction (P=0.007) and
congestive heart failure (P<0.00001) was observed. Notably, the incidence of mortality and
cardiac toxicity following concurrent and weekly use of
trastuzumab was significantly lower compared to treatment with
trastuzumab sequentially and every 3 weeks, respectively. Additionally,
trastuzumab improved the
pathologic complete response with no additional toxicity in the neoadjuvant setting. The present meta-analysis summarizes that
trastuzumab is efficacious in patients with HER-2 positive BC in adjuvant and neoadjuvant settings. Thus, concurrent and weekly administration of
trastuzumab is preferable to treatment with
trastuzumab sequentially and every 3 weeks. These findings should be considered when using
trastuzumab in future clinical practice.