Comparative Prognosis of HER2-Low versus HER2-Negative Breast Cancer: A Meta-Analysis

Area of Science:

• Oncology
• Translational Research
• Biomarker Discovery

Background:

• Emerging antibody-drug conjugates (ADCs) highlight human epidermal growth factor receptor 2 (HER2)-low expression as a potential therapeutic target in breast cancer (BC).
• Limited evidence currently exists on the prognostic significance of HER2-low BC despite ongoing clinical trials for new ADCs.

Purpose of the Study:

• To conduct a systematic meta-analysis comparing the prognostic value of survival outcomes in HER2-low versus HER2-negative breast cancer patients.
• To evaluate the impact of HER2-low status on overall survival (OS), disease-free survival (DFS), and pathological complete response (PCR) rates.

Main Methods:

• A systematic search of the Cochrane Library and PubMed was performed to identify 23 eligible retrospective or prospective studies.
• Data from 781,941 patients with HER2-low BC were pooled using a random-effects model to calculate hazard ratios (HRs) for OS and DFS, and odds ratios (ORs) for PCR.
• OS was the primary endpoint, with DFS and PCR rates as secondary endpoints.

Main Results:

• Patients with HER2-low BC demonstrated a significant improvement in OS compared to those with HER2-negative BC (HR = 0.82, P = 0.001).
• No significant difference in DFS was observed between HER2-low and HER2-negative BC groups (HR = 0.87, P = 0.28).
• A significantly lower PCR rate was found in patients with HER2-low BC compared to HER2-negative BC (OR = 0.88, P < 0.001).

Conclusions:

• HER2-low status is associated with significantly increased overall survival but decreased pathological complete response rates when compared to HER2-negative status in breast cancer.
• Disease-free survival does not show a significant increase in HER2-low breast cancer patients relative to HER2-negative patients.