HER2-Low Breast Cancer-Current Knowledge and Future Directions

Area of Science:

• Oncology
• Translational Research
• Biomarker Discovery

Background:

• The binary classification of HER2 (Human Epidermal growth factor Receptor 2) status in breast cancer is being re-evaluated.
• The DESTINY-Breast trial demonstrated significant efficacy of antibody-drug conjugates (ADCs) in patients with HER2-low expressing invasive breast cancer.
• HER2-low breast cancer is defined by immunohistochemistry (IHC) scores of 1+ or 2+ without HER2 gene amplification.

Purpose of the Study:

• To provide an updated review of HER2-low and HER2-ultralow breast cancer.
• To discuss the implications of recent clinical trial data on HER2 classification.
• To explore the evolving landscape of HER2 expression in breast cancer.

Main Methods:

• Literature review of key clinical trials, focusing on DESTINY-Breast.
• Analysis of the definition and characteristics of HER2-low and HER2-ultralow breast cancer.
• Discussion of current clinical guidelines and quality control issues.

Main Results:

• Antibody-drug conjugates (ADCs) show clinical benefit in HER2-low breast cancer, expanding treatment options beyond HER2-positive disease.
• HER2-low breast cancer is not a distinct biological entity but includes hormone receptor-positive and triple-negative subtypes.
• Differences in clinical behavior and response exist between HER2-low and HER2-null breast cancer.

Conclusions:

• The definition and clinical significance of HER2 expression in breast cancer are expanding beyond the traditional binary classification.
• HER2-low status represents a crucial therapeutic target for novel agents like ADCs.
• Further research and standardization are needed to optimize the identification and treatment of patients with HER2-low and HER2-ultralow breast cancer.