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ER staining levels affect HER2 staining and heterogeneity.

Momoko Akashi1,2, Rin Yamaguchi3,4, Hironori Kusano1

  • 1Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.

Breast Cancer (Tokyo, Japan)
|January 10, 2021
PubMed
Summary

High estrogen receptor (ER) expression in HER2-positive breast cancer correlates with increased HER2 heterogeneity and scoring discrepancies under updated guidelines. This highlights the need for careful HER2 assessment in ER-positive cases.

Keywords:
HER2 ASCO/CAP guidelineHER2 positive breast carcinomaHER2 staining; heterogeneityHormone receptor

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Area of Science:

  • Oncology
  • Pathology
  • Genetics

Background:

  • Accurate human epidermal growth factor receptor 2 (HER2) assessment is crucial for breast cancer treatment decisions.
  • Estrogen receptor (ER) expression levels may influence HER2 staining properties and heterogeneity.
  • Updates to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines in 2018 altered HER2 assessment criteria.

Purpose of the Study:

  • To investigate the relationship between ER expression levels and HER2 staining characteristics, including heterogeneity.
  • To evaluate differences in HER2 assessment between the 2013 and 2018 ASCO/CAP guidelines.
  • To analyze HER2/CEP17 ratio and HER2 copy number variations in different ER expression groups.

Main Methods:

  • Categorization of HER2-positive breast cancers into high (LH-high), low (LH-low), and negative (NLH) ER expression groups.
  • Comparison of HER2 immunohistochemistry (IHC) scores of 2+ and intratumor heterogeneity for HER2 IHC 3+ cases across ER groups.
  • Classification of in situ hybridization (ISH) groupings based on the 2018 ASCO/CAP guideline algorithm, including HER2/CEP17 ratio and average HER2 copy number.

Main Results:

  • The LH-high group showed a significantly higher prevalence of HER2 IHC 2+ scores (45/45 cases) and HER2 IHC 3+ heterogeneity (19/25 cases) compared to other groups.
  • A substantial proportion (39.5%) of cases with HER2 IHC 2+ in the LH-high group were reclassified as HER2-negative under the 2018 ASCO/CAP guidelines.
  • The NLH group exhibited a homogenous HER2 expression profile.

Conclusions:

  • The LH-high group is characterized by significant HER2 heterogeneity, often presenting with IHC scores of 2+ or 3+.
  • The 2018 ASCO/CAP guideline updates may lead to reclassification of HER2 status, particularly in ER-positive breast cancers.
  • ER expression levels are an important factor to consider in the interpretation of HER2 testing results.