Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer

Publication Date: June 7, 2023
Last Updated: June 7, 2023

Highlights

All newly diagnosed patients with breast cancer must have a HER2 test performed. Patients who then develop metastatic disease must have a HER2 test performed in a metastatic site, if tissue sample is available.
If a case has a HER2/CEP17 ratio is ≥2.0 but the average HER2 signals/cell is <4.0, a definitive diagnosis will be rendered based on additional workup. ( EB , I , S )
  • If not already assessed by the institution/lab performing the ISH test , IHC testing for HER2 should be performed using sections from the same tissue sample used for ISH and the slides from both ISH and IHC be reviewed together to guide the selection of areas to score by ISH (local practice considerations will dictate the best procedure to accomplish this concomitant assessment):
    • If the IHC result is 3+, diagnosis is HER2 POSITIVE
    • If the IHC result is 2+, recount ISH by having an additional observer, blinded to previous ISH results, count at least 20 cells that include the area of invasive cancer with IHC 2+:
      • If reviewing the count by the additional observer changes the result into another ISH category, the result should be adjudicated per internal procedures to define the final category.
      • If the count remains an average of <4.0 HER2 signals/cell and HER2/CEP17 ratio ≥2.0, the diagnosis is HER2 NEGATIVE with a comment.*
    • If the IHC result is 0/1+, diagnosis is HER2 NEGATIVE with a comment.*
      *Note: Refer to full text guideline for the specific comments associated with each recommendation.
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If a case has an average of ≥6.0 HER2 signals/cell with a HER2/CEP17 Ratio of <2.0, formerly diagnosed as ISH Positive for HER2, a definitive diagnosis will be rendered based on additional workup. ( EB , I , S )
  • If not already assessed by the institution/lab performing the ISH test , IHC testing for HER2 should be performed using sections from the same tissue sample used for ISH and the slides from both ISH and IHC be reviewed together to guide the selection of areas to score by ISH (local practice considerations will dictate the best procedure to accomplish this concomitant review):
    • If the IHC result is 3+, diagnosis is HER2 POSITIVE
    • If the IHC result is 2+, recount ISH by having an additional observer, blinded to previous ISH results, count at least 20 cells that include the area of invasive cancer with IHC 2+ staining:
      • If reviewing the count by the additional observer changes the result into another ISH category, the result should be adjudicated per internal procedures to define the final category.
      • If the HER2/CEP17 ratio remains <2.0 with ≥6.0 HER2 signals/cell, the diagnosis is HER2 POSITIVE .*
    • If the IHC result is 0/1+, diagnosis is HER2 NEGATIVE with a comment.*
      *Note: Refer to full text guideline for the specific comments associated with each recommendation.
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If the case has an average HER2 signals/tumor cell of ≥4.0 and <6.0 HER2 signals/cell and HER2/CEP17 Ratio is <2.0, formerly diagnosed as ISH Equivocal for HER2, a definitive diagnosis will be rendered based on additional workup. ( EB , I , S )
  • If not already assessed by the institution/lab performing the ISH test, IHC testing for HER2 should be performed using sections from the same tissue sample used for ISH and the slides from both ISH and IHC be reviewed together to guide the selection of areas to score by ISH (local practice considerations will dictate the best procedure to accomplish this concomitant review):
    • If the IHC result is 3+, diagnosis is HER2 POSITIVE
    • If the IHC result is 2+, recount ISH by having an additional observer, blinded to previous ISH results, count at least 20 cells that include the area of invasive cancer with IHC 2+:
      • If reviewing the count by the additional observer changes the result into another ISH category, the result should be adjudicated per internal procedures to define the final category.
      • If the count remains an average of ≥4.0 and <6.0 HER2 signals/cell with HER2/CEP17 ratio <2.0, the diagnosis is HER2 NEGATIVE with a comment.*
    • If the IHC result is 0/1+, diagnosis is HER2 NEGATIVE with a comment.*
      *Note: Refer to full text guideline for the specific comments associated with each recommendation.
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If the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may be ordered on the excision specimen if one of the following is observed: (EB, H, S)
Tumor is grade 3

Amount of invasive tumor in the core biopsy is small

Resection specimen contains high-grade carcinoma that is morphologically distinct from that in the core

Core biopsy result is equivocal for HER2 after testing by both ISH and IHC

There is doubt about the specimen handling of the core biopsy (long ischemic time, short time in fixative, different fixative) or the test is suspected by the pathologist to be negative on the basis of testing error
ᵃ Criteria to consider if there are concerns regarding discordance with apparent histopathologic findings and possible false-negative or false-positive HER2 test result.
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Recommendation Grading

Overview

Title

Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer

Authoring Organizations

American Society of Clinical Oncology

College of American Pathologists

Publication Month/Year

June 7, 2023

Last Updated Month/Year

September 30, 2024

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor 2 (HER2) testing in breast cancer guideline.

Target Patient Population

Patients with breast cancer

Target Provider Population

Medical oncologists, pathologists, surgeons, and radiation oncologists.

PICO Questions

What is the optimal testing algorithm for the assessment of human epidermal growth factor receptor 2 (HER2) status and what strategies can help ensure optimal performance, interpretation, and reporting of established assays?

Inclusion Criteria

Female, Adult, Older adult

Health Care Settings

Ambulatory, Laboratory services, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening

Keywords

HER2, HER2 Testing

Source Citation

Wolff AC et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO-CAP Guideline Update. J Clin Oncol. 2023 June 7 DOI: 10.1200/JCO.22.02864

Supplemental Methodology Resources

Data Supplement, Methodology Supplement, Evidence Tables

Methodology

Number of Source Documents
222
Literature Search Start Date
January 1, 2013
Literature Search End Date
May 11, 2017
Public Comment Process Start Date
May 22, 2017
Public Comment Process End Date
June 19, 2017
Specialties Involved
Oncology, Pathology, Clinical Pathology, Medical Oncology, Surgical Oncology, Radiation Oncology, Pathology, Oncology, Oncology, Oncology