HER2-low breast cancers: Current insights and future directions

Area of Science:

• Oncology
• Pathology
• Translational Research

Background:

• The emergence of HER2-targeting antibody-drug conjugates, such as trastuzumab-deruxtecan (T-Dxd), has highlighted the clinical significance of HER2-low expressing breast cancers.
• HER2-low breast cancer, defined by specific immunohistochemistry (IHC) scores (1+ or 2+ without gene amplification), is a newly recognized and actively investigated subtype.
• Recent Phase I and III clinical trials demonstrate substantial benefits of novel therapeutics in this patient population.

Purpose of the Study:

• To provide an updated review of cutting-edge research concerning HER2-low breast cancers.
• To focus on the underlying biology of HER2-low breast cancer.
• To address challenges in the pathological identification of HER2-low breast cancer and explore future research directions.

Main Methods:

• Review of recent clinical trials (Phase I and III) involving HER2-targeting antibody-drug conjugates.
• Analysis of current immunohistochemistry (IHC) methodologies for HER2 assessment in breast cancer.
• Synthesis of emerging research on the biological characteristics of HER2-low tumors.

Main Results:

• Novel antibody-drug conjugates, particularly T-Dxd, exhibit significant clinical efficacy in advanced HER2-low breast cancer.
• The definition and diagnostic criteria for HER2-low breast cancer are evolving, impacting patient stratification.
• Pathological assessment of HER2 status requires careful consideration to accurately identify this subgroup.

Conclusions:

• HER2-low breast cancer represents a distinct and treatable entity with significant therapeutic potential.
• Standardization of diagnostic methods is crucial for consistent identification and treatment of HER2-low breast cancer patients.
• Continued research into the biology and therapeutic strategies for HER2-low breast cancer is warranted.