PATHWAY anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody Identifying HER2-low expression

A women who has tested with low HER2 expression and is now eligible for targeted therapy.

The first and only FDA approved CDx for HER2-low expression
 

Now FDA approved as a companion diagnostic for the breakthrough designated therapy ENHERTU®* (fam-trastuzumab deruxtecan-nxki), PATHWAY anti-HER2/neu (4B5) Rabbit Monoclonal Antibody is the FIRST and ONLY test to identify metastatic breast cancer (mBC) patients with low expression of HER2 who may be eligible for targeted therapy.

PATHWAY anti-HER-2/new (4B5) Rabbit Monoclonal Primary Antibody Breast Cancer Interpretation Guide.

Complete the form to receive the PATHWAY anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody Interpretation Guide and the new Package Insert.

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*For more information on ENHURTU® please refer to the FDA-approved product labeling

FDA approved PATHWAY anti-HER2/neu (4B5) Rabbit Monoclonal Antibody to identify metastatic breast cancer patients with low HER2 expression for whom ENHERTU may be considered

Previously, there were no HER2-directed treatment options for the more than 50 percent of patients with mBC who were considered HER2-negative. Now, thanks to advances in drug development targeting lower ranges of HER2 expression and the diagnostic innovation of Roche, these patients may qualify for personalized treatment that could potentially lead to improved outcomes.
 
  • The Roche PATHWAY HER2 (4B5) assay1 has shown the most consistent performance and superior quality when compared to other on-market HER2 clones.2
  • The new HER2-low indication uses the proven technology of the PATHWAY anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody. The FDA approved HER2-low indication uses a lower scoring cut-off, allowing patient stratification within a new subtype of breast cancer that has some HER2 proteins on the cell surface, but not enough to be classified as HER2-positive.12
  • Indicated as an aid in the assessment of patients with HER2-low status for whom ENHERTU is being considered as a treatment option.
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1. Tarantino, P. et al. (2020). Journal of Clinical Oncology, 8(17):1951-1962. All Accessed 7/15/2022

2. Based on data from a leading external quality assessment scheme. Retrieved from http://www.nordiqc.org/epitope.php

 

PATHWAY anti-HER2/neu (4B5) is a registered trademark of Roche Diagnostics

Confidently Navigate the complexities
of HER2 IHC testing in Breast Cancer
 

Join Roche to learn more about scoring and clinical significance of the newest companion
diagnostic indication of PATHWAY anti-HER2 (4B5) for HER2-low.

HER2-low Webinar Sign Up

Indication for use: breast cancer

View Full Table

Indication for use: breast cancer

Table 1. PATHWAY anti-HER2 (4B5) Antibody Companion Diagnostic Indications.
Breast Cancer  Staining Pattern Score Recommended Reporting Status Clinical Application

No membrane staining is observed

OR

Faint, partial staining of the membrane in 10% or LESS of the cancer cells*

0 HER2 Negative None
Faint, partial staining of the membrane in greater than 10% of the cancer cells* 1+ HER2-low expression

ENHERTU®

(fam-trastuzumab deruxtecan-nxki)

Weak to moderate complete staining of the membrane in greater than 10% of the cancer cells Positve Weak to moderate complete staining of the membrane in greater than 10% of the cancer cells Positve

2+*

Reflex test: HER2 Non-Amplified

HER2-low expression

2+*

Reflex test: HER2 Amplified

HER2 Positive/overexpression

Herceptin® (trastuzumab),

KADCYLA® (trastuzumab emtansine)

Intense complete staining of the membrane in greater than 10% of the cancer cells 3+ HER2 Positive/overexpression
*Recommend re-reading by a second pathologist for cases with “faint, partial staining of the membrane” and %TC near the threshold of 10%, when the range of %TC is between 5%-25%
**Recommend reflex test to assess gene amplification per ASCO/CAP guidance

A diverse group of women diagnosed with breast cancer with HER2 low expression.

Frequently Asked Questions

Frequently Asked Questions

HER2-low is a recently defined subtype of breast cancer categorized as “...faint, partial staining of the membrane in greater than 10% of the cancer cells” or “...weak to moderate complete staining of the membrane in greater than 10% of the cancer cells…” and has a HER2 /chromosome 17 ratio of less than 2.0 by a in situ hybridization assay.2-4  In current guidelines, these categories are called 1+ or 2+, non-amplified.6 Although both 1+ and 2+ have historically been considered ineligible for HER2 targeted therapies, such as trastuzumab, data from the pivotal Phase III DESTINY-Breast04 clinical trial data demonstrates that patients with metastatic breast cancer classified as HER2-low derive substantial clinical benefit from fam-trastuzumab deruxtecan (ENHERTU®) in the second line setting8 and enables a new treatment approach for patients that lacked treatment options.

Roche recommends that a freshly cut section of archived or recently collected sample of FFPE breast cancer be stained using the PATHWAY HER2 4B5 assay, using the locked staining procedure, U PATHWAY HER2 4B5 for the assessment of HER2-low.11

  • All patients will have likely received previous diagnostic testing to determine their HER2 and HR status.  These previous findings will be documented in the patient record and depending on institutional practices, stained glass slides may be archived.  While the patient's historic record will provide a HER2 score and archived slides could be requested for review, but there are potential issues that may prevent accurate assessment of HER2-low with archived results and slides. 

Roche recommends that a freshly cut section of archived or recently collected sample of FFPE breast cancer be stained using the PATHWAY HER2 4B5 assay, using the locked staining procedure, U PATHWAY HER2 4B5 for the assessment of HER2-low.11

  • All patients will have likely received previous diagnostic testing to determine their HER2 and HR status.  These previous findings will be documented in the patient record and depending on institutional practices, stained glass slides may be archived.  While the patient's historic record will provide a HER2 score and archived slides could be requested for review, but there are potential issues that may prevent accurate assessment of HER2-low with archived results and slides.
  • Since the first publication of the practice guidelines for the diagnostic assessment of HER2 in breast cancer in 20077, the guidelines have been updated twice in 2013 and 20181,6
  • Several HER2 IHC assays have been used routinely since the first evidence of IHC testing for HER2 positive targeted therapy8.  As such, historic HER2 scores may have been determined using a HER2 IHC assay other than the PATHWAY HER2 4B5 assay.
  • Staining protocols outside of the currently validated staining protocol for the PATHWAY HER2 4B5 assay may have been implemented at the time of diagnosis. 
  • Although DAB is a stable relative to other chromogens used for IHC, fading does occur over time9-10. Based on this potential limitation, archived glass slides stained with the PATHWAY HER2 4B5 assay may not have the same staining intensity as when they were initially reviewed. 
  • The inability to accurately evaluate the role that these factors play in determining the initial diagnosis should be considered before using archived slides or the historic HER2 IHC score to determine HER2-low status.

The PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody was the only HER2 IHC assay used to select patients for the pivotal DESTINY-Breast04 clinical trial4 and is the only HER2 IHC assay approved by the FDA for determining patient eligibility for fam-trastuzumab deruxtecan-nxki treatment.  Other HER2 IHC assays have not been validated in prospective clinical trials for fam-trastuzumab deruxtecan-nxki treatment.

While Roche has not evaluated the Pathway HER2 4B5 assay against other HER2 antibodies, data has shown that the Pathway HER2 4B5 antibody displays more sensitivity at the 1+ bin than another HER2 assay5.

  1. Wolff, A., Hammond, E., Allison, K., Harvey, B. et al. . Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/ College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Onco 36, 2105-2122, doi:10.1200/JCO10.1200/JCO.2018 (2018).
  2. Tarantino, P. et al. HER2-Low Breast Cancer: Pathological and Clinical Landscape. J Clin Oncol 38, 1951-1962, doi:10.1200/JCO.19.02488 (2020).
  3. Zhang, H., Katerji, H., Turner, B. M. & Hicks, D. G. HER2-Low Breast Cancers. Am J Clin Pathol 157, 328-336, doi:10.1093/ajcp/aqab117 (2022).
  4. Modi, S. et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med 387, 9-20, doi:10.1056/NEJMoa2203690 (2022).
  5. Scott, M., Vandenberghe, M. E., Scorer, P., Boothman, A.-M. & Barker, C. Prevalence of HER2-low in breast cancer subtypes using the VENTANA anti-HER2/neu (4B5) assay. Journal of Clinical Oncology 39, 1021-1021, doi:10.1200/JCO.2021.39.15_suppl.1021 (2021).
  6. Wolff, A. C. et al. Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update. Journal of Clinical Oncology 31, 3997-4013, doi:10.1200/jco.2013.50.9984 (2013).
  7. Wolff, A. C. et al. American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer. Journal of Clinical Oncology 25, 118-145, doi:10.1200/jco.2006.09.2775 (2007).
  8. Arnould, L. et al. Pathologic complete response to trastuzumab-based neoadjuvant therapy is related to the level of HER-2 amplification. Clin Cancer Res 13, 6404-6409, doi:10.1158/1078-0432.CCR-06-3022 (2007).
  9. Ormerod, M. G. & Imrie, S. F. Enzyme-antienzyme method for immunohistochemistry. Methods Mol Biol 10, 117-124, doi:10.1385/0-89603-204-3:117 (1992).
  10. Van Eycke, Y. R., Allard, J., Salmon, I., Debeir, O. & Decaestecker, C. Image processing in digital pathology: an opportunity to solve inter-batch variability of immunohistochemical staining. Sci Rep 7, 42964, doi:10.1038/srep42964 (2017).
  11. PATHWAY HER2/neu Rabbit Monoclonal Primary Antibody Method Sheet  14427US Rev H  22-04-29
  12. https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-her2-low-breast-cancer : Accessed October 2, 2022.
IHC Slide Stain Indicating HER2 Low Expression

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