Pertuzumab and Pathological Complete Response in Early HER2+ Breast Cancer: A Systematic Review and Meta-analysis of Real-World Studies

BACKGROUND: Human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) is an aggressive subtype that is associated with poorer outcomes. Neoadjuvant chemotherapy combined with trastuzumab has significantly improved prognosis, and the addition of pertuzumab has further enhanced the treatment response. Pathological complete response (pCR) is a reliable surrogate marker of long-term outcomes, and its achievement can inform surgical and adjuvant therapy decisions. While randomized controlled trials (RCTs) have demonstrated the benefits of dual HER2 blockade, real-world evidence (RWE) is critical for assessing treatment effectiveness in broader, more diverse populations. OBJECTIVE: To evaluate the impact of dual HER2 blockade with pertuzumab and trastuzumab compared to single-agent trastuzumab on pCR rates in early-stage HER2+ breast cancer using real-world data. METHODS: A systematic review and meta-analysis were conducted using the PubMed, Embase, and Scopus databases from inception to February 28, 2025. Eligible studies were retrospective or prospective real-world investigations comparing neoadjuvant chemotherapy with trastuzumab alone versus trastuzumab plus pertuzumab. Data were extracted independently by two reviewers. Pooled odds ratios (ORs) for pCR, along with 95% confidence intervals (CIs), were calculated. The risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: Eighteen studies involving 8,651 patients met the inclusion criteria. The pooled odds ratio (OR) showed significantly higher pCR rates with dual HER2 blockade (OR: 1.81; 95% CI: 1.56-2.09), with no observed heterogeneity (I² = 0%). Subgroup analyses confirmed consistent findings across geographic regions and study characteristics. Publication bias was low, as supported by Egger's test (p = 0.37). CONCLUSION: In real-world settings, adding pertuzumab to neoadjuvant therapy significantly improves pCR rates in early-stage HER2+ breast cancer, aligning with RCT evidence. These findings support the broader adoption of dual HER2 blockade and highlight the need for further prospective real-world studies to refine treatment strategies for specific patient subgroups.