Pathological complete response as a surrogate to improved survival in human epidermal growth factor receptor-2-positive breast cancer: systematic review and meta-analysis

Background: Achieving a pathological complete response (pCR) is believed to correlate with oncological outcomes in human epidermal growth factor receptor-2-positive (HER2+) breast cancer. However, informed estimation of this survival advantage is often difficult to quantify. The aim of this study was to evaluate the role of pCR as a biomarker of survival in patients treated with neoadjuvant therapies for HER2+ breast cancer.

Methods: A systematic review was performed in accordance with the PRISMA checklist. Data specific to pCR and survival with respect to event-free survival (EFS), recurrence-free survival (RFS) and overall survival (OS) were expressed as hazard ratio (HR) and 95 per cent confidence intervals (c.i.). pCR and survival at yearly intervals after resection were expressed as dichotomous variables using the Mantel-Haenszel method.

Results: Overall, 78 clinical studies with 25 150 patients were included in this study. pCR predicted better EFS (HR 0.67, 95 per cent c.i. 0.60 to 0.74; 41 studies), RFS (HR 0.69, 95 per cent c.i. 0.57 to 0.83; 18 studies) and OS (HR 0.63, 95 per cent c.i. 0.56 to 0.70; 29 studies) for patients with HER2+ breast cancer. At 5 years, pCR predicted better EFS (HR 0.37, 95 per cent c.i. 0.30 to 0.48; 19 studies), RFS (HR 0.28, 95 per cent c.i. 0.21 to 0.39; 8 studies) and OS (HR 0.26, 95 per cent c.i. 0.20 to 0.33; 10 studies).

Conclusion: This study confirms pCR as an informative surrogate biomarker for enhanced survival and suggests that it may be used as an appropriate endpoint for clinical research.