Neoadjuvant therapy with vs. without anthracyclines for HER2-positive breast cancer: a systematic review and meta-analysis

BACKGROUND: Neoadjuvant therapy has become the standard treatment for early human epidermal growth factor receptor 2 (HER2)-positive breast cancer, with most regimens using a combination of anti-HER2-targeted drugs and chemotherapy. However, the combination of anthracyclines and trastuzumab has high cardiac toxicity, and the efficacy evaluation of targeted therapy with or without anthracyclines is not unified. The purpose of this meta-analysis was to evaluate the relative efficacy and safety of anti-HER2-targeted therapy combined with vs. without anthracyclines neoadjuvant treatment. METHODS: The following databases: PubMed, Medline, Embase, and Cochrane Library were systematically searched. Study inclusion was determined according to PICOS principles. PICOS: Patients, HER2-positive breast cancer; Intervention, anti-HER2-targeted therapy combined with anthracyclines; Control, without anthracyclines; Outcomes, the percentage of pathologic complete response (pCR), breast-conserving surgery (BCS), and grade 3 or worse adverse events according to CTCAE version 4.03; Studies, randomized controlled trials (RCTs) and retrospective studies. The meta-analysis was performed using RevMan5.3 software, and the odds ratio (OR) with 95% confidence intervals (CIs) was performed. RESULTS: In total, 11 articles involving 1,998 patients were included with 1,155 patients in the anthracycline-containing group and 843 patients in the anthracycline-free group. For efficacy, there was no statistically significant difference in the percentage of pCR (OR 0.95; 95% CI: 0.61–1.48; P=0.83) and BCS (OR 1.18; 95% CI: 0.93–1.49; P=0.17) on anthracycline-free regimens compared with anthracycline-containing regimens. For safety, the combined effect values showed a significantly lower incidence of left ventricular ejection fraction decreases with the anthracycline-free regimen than with the anthracycline-containing regimen (OR 0.50; 95% CI: 0.35–0.71; P=0.0001). Other adverse effects and survival events were generally not statistically different in incidence between the two groups. The subgroup analysis suggested that hormone receptor status might be the source of heterogeneity in this study. CONCLUSIONS: Our study demonstrated that the targeted therapy combined with anthracyclines was associated with an increased risk of cardiac adverse events compared with the anthracycline-free group, with no significant difference in the percentage of pCR and BCS. Due to the high heterogeneity of this meta-analysis, more studies with longer follow-up are needed to validate the current findings and to further explore the removal and retention of anthracyclines.