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Updated recommendation to HER2 IHC testing for mNSCLC patients

The December 2024 update to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer (NSCLC) V.1.2025 included recommendations for HER2 IHC testing.¹ This marked the first time that the guidelines recommended testing for multiple HER2 alterations in mNSCLC via separate testing methods.¹

NCCN Guidelines® recommend the following HER2 tests for mNSCLC patients¹:

HER2 IHC testing to assess for HER2 protein overexpression (IHC 3+): HER2 IHC testing is recommended at some point during progression.*
NGS testing to assess for HER2 (ERBB2) gene mutations: Complete genotyping for key biomarkers including HER2 (ERBB2) mutations using a broad panel approach is recommended; testing using peripheral blood (most commonly plasma-based testing of ctDNA) can be utilized in conjunction with tissue-based testing to achieve genotyping for recommended biomarkers.**

*Timing should be balanced with tissue conservation.¹ **Targeted PCR techniques can also be utilized to examine HER2 (ERBB2) mutations. Testing for HER2 (ERBB2) gene amplification is only recommended for EGFR TKI resistance or clinical trial eligibility.¹

HER2 test concordance:

In mNSCLC, HER2 protein overexpression (IHC 3+) and HER2 (ERBB2) gene mutations are separate biological events requiring specific testing methods.^2,3 IHC is used to test for protein overexpression and NGS for gene mutations and other genomic alterations.^3,4 Separately conducting HER2 IHC testing, regardless of NGS results, helps ensure a more complete assessment of HER2 protein overexpression for mNSCLC patients.¹

HER2 IHC scoring criteria:

For NSCLC, gastric scoring criteria can be utilized for HER2 IHC assessment, which employs different scoring criteria for small biopsy specimens versus resections.¹

Criteria for HER2 IHC 3+
based on ASCO-ASCP-CAP gastric guidelines⁵

Surgical specimens

Biopsy specimens

Strong complete, basolateral, or lateral membrane staining in ≥10% of tumor cells

Strong complete, basolateral, or lateral membrane staining in a tumor cell cluster (≥5 tumor cells), irrespective of percentage of tumor cells stained

HER2 reporting in NSCLC:

The CAP’s lung biomarker reporting template includes fields to report results of HER2 IHC testing and other HER2 test results.⁶

View the latest NCCN Guidelines and start HER2 IHC testing to inform patient care

View latest NCCN Guidelines

For more guidance on HER2 alterations and IHC testing in NSCLC and other solid tumors, view the resources below.

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

ASCO, American Society of Clinical Oncology; ASCP, American Society for Clinical Pathology; CAP, College of American Pathologists; EGFR, epidermal growth factor receptor; ERBB2, erb-b2 receptor tyrosine kinase 2; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; mNSCLC, metastatic non-small cell lung cancer; NCCN, National Comprehensive Cancer Network; NGS, next-generation sequencing; NSCLC, non-small cell lung cancer; PCR, polymerase chain reaction; TKI, tyrosine kinase inhibitor.

1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Non-Small Cell Lung Cancer V.7.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed July 10, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. 2. Uy NF, et al. Cancers (Basel) 2022;14(17):4155. 3. Ninomiya K, et al. Chest 2019;156(2):357-366. 4. Hechtman JF and Ross DS. Cancer Cytopathol 2019;127(7):428-431. 5. Bartley AN, et al. J Clin Oncol 2017;35(4):446-464. 6. CAP Template for Reporting Results of Biomarker Testing of Specimens From Patients With Non-Small Cell Carcinoma of the Lung. Version 2.0.1.1. Available at: https://documents.cap.org/protocols/
Lung.Bmk_2.0.1.1.REL_CAPCP.pdf. Accessed: March 2025.

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CAP Biomarker Reporting Templates

The College of American Pathologists provides guidance on HER2 IHC reporting in biomarker reporting templates for Gastric, Colorectal, Gynecological, Lung, Head & Neck, and General IHC Quantitative Biomarkers.

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HER2 Can Be Here, Too: HER2 testing in solid tumors

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Updated recommendation to HER2 IHC testing for mNSCLC patients

NCCN Guidelines® recommend the following HER2 tests for mNSCLC patients¹:

HER2 test concordance:

HER2 IHC scoring criteria:

HER2 reporting in NSCLC:

Related resources

GUIDELINES

CAP Biomarker Reporting Templates

The College of American Pathologists provides guidance on HER2 IHC reporting in biomarker reporting templates for Gastric, Colorectal, Gynecological, Lung, Head & Neck, and General IHC Quantitative Biomarkers.

Guide

HER2 Can Be Here, Too: HER2 testing in solid tumors

Introduction to HER2 IHC testing across solid tumors, with guidance on scoring and reporting in endometrial, cervical, ovarian, non-small cell lung, bladder, colorectal and other solid tumor types.

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Ordering HER2 testing for patients with NSCLC

Clinical care team’s guide to HER2 testing in non-small cell lung cancer, with information on ordering HER2 IHC testing.

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Gastric Cancer Links

Other Solid Tumors Links

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Updated recommendation to HER2 IHC testing for mNSCLC patients

NCCN Guidelines® recommend the following HER2 tests for mNSCLC patients1:

HER2 test concordance:

HER2 IHC scoring criteria:

HER2 reporting in NSCLC:

Related resources

GUIDELINES

CAP Biomarker Reporting Templates

The College of American Pathologists provides guidance on HER2 IHC reporting in biomarker reporting templates for Gastric, Colorectal, Gynecological, Lung, Head & Neck, and General IHC Quantitative Biomarkers.

Guide

HER2 Can Be Here, Too: HER2 testing in solid tumors

Introduction to HER2 IHC testing across solid tumors, with guidance on scoring and reporting in endometrial, cervical, ovarian, non-small cell lung, bladder, colorectal and other solid tumor types.

CLINICAL CARE TEAM GUIDE

Ordering HER2 testing for patients with NSCLC

Clinical care team’s guide to HER2 testing in non-small cell lung cancer, with information on ordering HER2 IHC testing.

Quick Links

Breast Cancer Links

Gastric Cancer Links

Other Solid Tumors Links

About Us

Legal

What is a Daiichi Sankyo Company or AstraZeneca authorized person?

NCCN Guidelines® recommend the following HER2 tests for mNSCLC patients¹: