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Related Experiment Videos

Hormone Receptor and HER2 Testing in Breast Cancer: Latest Questions Answered.

Joanna Solarewicz1, Kimberly H Allison1

  • 1Department of Pathology, Stanford Medicine, 300 Pasteur Drive, Stanford, CA, USA.

Surgical Pathology Clinics
|November 12, 2025
PubMed
Summary

Pathologists must update breast cancer biomarker reporting for estrogen receptor (ER) low positive and HER2 low/ultralow cases. These classifications impact treatment decisions, particularly endocrine therapy and eligibility for targeted therapies like trastuzumab-deruxtecan.

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Area of Science:

  • Oncology
  • Pathology
  • Biomarker Analysis

Background:

  • Evolving data necessitate adjustments in breast cancer biomarker interpretation.
  • Estrogen receptor (ER) low positive and HER2 low/ultralow are not distinct subtypes but have significant treatment implications.
  • Accurate HER2 assessment is crucial for targeted therapy eligibility.

Purpose of the Study:

  • To highlight the evolving landscape of breast cancer biomarker interpretation.
  • To emphasize the clinical significance of ER low positive and HER2 low/ultralow classifications.
  • To address the necessity of precise HER2 distinction for treatment guidance.

Main Methods:

  • Review of current breast cancer biomarker interpretation guidelines.
  • Analysis of clinical trial data (e.g., DESTINY-Breast 04/06) defining HER2 low/ultralow categories.
Keywords:
ER low positiveEstrogen receptor (ER)HER2HER2 lowHER2 ultralowProgesterone receptor (PR)

Related Experiment Videos

  • Discussion of diagnostic challenges in HER2 immunohistochemistry (IHC) scoring.
  • Main Results:

    • ER low positive (1%-10%) cancers, while resembling ER-negative tumors, may benefit from endocrine therapy.
    • HER2 low and ultralow status, as defined in key trials, determines eligibility for trastuzumab-deruxtecan in metastatic breast cancer.
    • Distinguishing between HER2 IHC 0 (no staining) and 0+ (some staining) is now clinically essential.

    Conclusions:

    • Pathologists must adapt reporting to reflect the treatment implications of ER low positive and HER2 low/ultralow breast cancer.
    • Precise HER2 IHC scoring is critical for patient selection for novel therapies, despite ongoing concerns about reproducibility.
    • These evolving biomarker interpretations are vital for optimizing breast cancer treatment strategies.