Do HER2-Low Tumors Have a Distinct Clinicopathologic Phenotype?

Area of Science:

• Oncology
• Pathology
• Genomics

Background:

• Breast cancer is classified into subtypes based on hormone receptor (HR) and HER2 status, influencing clinical behavior.
• The emerging category of HER2-low breast cancer has prompted investigation into its distinct clinicopathologic features.

Purpose of the Study:

• To determine if HER2-low breast cancers exhibit unique clinicopathologic characteristics differentiating them from HER2-negative and HER2-positive breast cancers.
• To evaluate the association of HER2-low status with various clinicopathologic variables, including lymphovascular invasion, multifocality, and nodal status.

Main Methods:

• Analysis of 11,072 patients undergoing upfront surgery from 1998-2010.
• Classification of HER2 status using immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH): HER2 negative, HER2 low (IHC 1+ or 2+ with negative FISH), and HER2 positive.
• Univariate and multivariable logistic regression analyses were performed, stratifying by HR status.

Main Results:

• HER2-low tumors showed associations with lymphovascular invasion, multifocality, and nodal micrometastasis compared to HER2-negative tumors.
• While age and multifocality were associated with HER2-low on univariate analysis, no variables independently distinguished HER2-low from HER2-negative tumors across both HR-positive and HR-negative groups.
• HER2-positive tumors were associated with multifocality and extensive intraductal components, irrespective of HR status.

Conclusions:

• The clinicopathologic features of HER2-low breast cancer are predominantly linked to hormone receptor status.
• The study's findings do not support the classification of HER2-low as a distinct subtype of breast cancer.