J Pathol Transl Med.  2020 Jan;54(1):34-44. 10.4132/jptm.2019.11.03.

HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation

• Ahn S
• Woo JW
• Lee K
• Park SY

• KMID: 2501593
• DOI: http://doi.org/10.4132/jptm.2019.11.03

Abstract

Human epidermal growth factor receptor 2 (HER2) protein overexpression and/or HER2 gene amplification is found in about 20% of invasive breast cancers. It is a sole predictive marker for treatment benefits from HER2 targeted therapy and thus, HER2 testing is a routine practice for newly diagnosed breast cancer in pathology. Currently, HER2 immunohistochemistry (IHC) is used for a screening test, and in situ hybridization is used as a confirmation test for HER2 IHC equivocal cases. Since the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines on HER2 testing was first released in 2007, it has been updated to provide clear instructions for HER2 testing and accurate determination of HER2 status in breast cancer. During HER2 interpretation, some pitfalls such as intratumoral HER2 heterogeneity and increase in chromosome enumeration probe 17 signals may lead to inaccurate assessment of HER2 status. Moreover, HER2 status can be altered after neoadjuvant chemotherapy or during metastatic progression, due to biologic or methodologic issues. This review addresses recent updates of ASCO/CAP guidelines and factors complicating in the interpretation of HER2 status in breast cancers.

Keyword

Breast cancer; HER2; ASCO/CAP guidelines; HER2 heterogeneity; CEP17 copy number gain

Figure

• 

  Fig. 1. Representative examples of human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) in breast cancer. (A) HER2 IHC negative (0). (B) HER2 IHC negative (1+). (C) HER2 IHC equivocal (2+). (D) HER2 IHC positive (3+).

• 

  Fig. 2. A representative breast cancer with intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity. (A) HER2 immunohistochemistry shows heterogeneous expression with strong, complete membranous expression on the right, and weak to moderate, incomplete membranous expression on the left. (B) HER2 silver in situ hybridization reveals high-level amplification on the right and no amplification on the left (inset, area of high-level amplification).

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