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HER2: Expressing potential beyond breast cancer

Why the HER2 biomarker is back in the spotlight

Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2), also known as HER2, is driving new developments across a variety of cancer types

HER2 is well-established biomarker with a history of prognostic and predictive utility. Overexpression and amplification of this oncogene drives deregulation of several key signaling pathways. It is through this deregulation of cell signaling that HER2 can promote cell growth, proliferation and apoptosis. However, we now have evidence showing that HER2 may play an important part for understanding solid tumours.

  • Amplification or overexpression of HER2 occurs in approximately 15-30% of breast cancers and 10-30% of gastroesophageal cancers. Overexpression of HER2 has also been noted in cancer of the ovaries, endometrium, bladder, lung, colon, head and neck.1

Reignited interest in the potential of HER2-related applications stems, of course, from the impact of its ground-breaking beginnings.

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HER2 back then

 

In 1998, we saw the first-ever companion diagnostic test alongside the FDA approval of Herceptin® (trastuzmab). The test identifies excessive levels of HER2 in a tumour, indicating that Herceptin® could be an effective treatment for those patients.

This revolutionary pairing transformed breast cancer treatment and paved the way for future therapies to come to fruition.2,3

Explore the key factors driving advancement in HER2

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Biomarker understanding and indications

HER2 status may play a role in treating or diagnosing breast, gastric, ovarian, bladder and pancreatic cancers.1

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Advancements in diagnostics

Digital image analysis provides an objective and reproducible alternative to manual scoring which could reduce misdiagnoses of HER2 cases and increase efficiencies in clinical practice.

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Updates in therapies and treatment options

Recent treatment strategies look to combine both immunotherapy (indirect) and targeted therapy (direct), opening the potential for more personalised care.4,5

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HER2 going forward - the way we understand HER2 has changed.

 

New strategies for direct and indirect oncogene targeting are impacting the ways we diagnose and treat cancer, increasing personalized treatment options that lead to better outcomes for patients. Direct HER2 targeting now includes novel, high-affinity anti-HER2 antibodies, antibody-drug conjugates (ADC), bispecific antibodies, and HER2-specific tyrosine kinase inhibitors (TKI).

More recent approaches to indirectly target HER2 are further advancing our approach to testing - from immune checkpoint inhibitors (ICIs) to cell cycle and PI3K inhibitors. Employing both direct and indirect targeting strategies can provide insights into the predictive and prognostic value of HER2 as a biomarker across a variety of cancer types.

Explore in-progress HER2-related studies:
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Beyond these innovative strategies, further advancements in instrumentation and workflows will soon increase accessibility to HER2 testing that will allow for earlier detection of tumours across a variety of different indications

 

  • Increased automation in immunohistochemistry (IHC) will help to streamline processes while reducing error, improving accuracy, and supporting higher throughput demands. Pathologists will continue to play a crucial role in HER2 testing and scoring to help ensure appropriate patient selection and successful clinical outcomes.6
  • Companion diagnostics are in development that will likely streamline clinical decision-making, marking a notable shift in the way we approach cancer care.
  • Digital image analysis solutions provide an objective and reproducible alternative to manual scoring, potentially reducing the number of 2+ HER2 cases sent for in-situ hybridization (ISH) testing.7

These exciting developments are helping to drive increased accessibility to accurate diagnostics, thereby increasing the potential for improved care for people everywhere, but this is just the beginning.

Our growing understanding of cancer is fueling the development of more advanced strategies for detection and treatment. As personalised patient care continues to become mainstream practice. more and more people will benefit from new innovative solutions and life-changing therapies.

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    References

    1. Iqbal N, Iqbal N. Human Epidermal Grow Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications. Mol Biol Int. 2014;2014:852748
    2. Shah, S Chen B. Testing for HER2 in Breast Cancer: A Continuing Evolution. Patholog Res Int. 210;210:903202
    3. Perez A, Cortes J, Gonzalez-Angulo AM, Bartlett JMS. HER2 testing: Current Status and future directions. Cancer Treat Rev. 2014;40(2):205-340
    4. Int. J. Mol. Sci. 2016, 17, 2095; doi:10.3390/ijms17122095
    5. Signal Transduction and Targeted Therapy (2019) 4:34; https://doi.org/10.1038/s41392-019-0069-2
    6. Buza N. HER2 Testing in Endometrial Serous Carcinoma: Time for Standardized Pathology Practice to Meet the Clinical Demand. Arch Pathol Lab Med. 2021;145(6):687-691.
    7. Koopman T, Buikema HJ, Hollema H, de Bock GH, van der Vegt B. What is the added value of digital image analysis of HER2 immunohistochemistry in breast cancer in clinical practice? A study with multiple platforms. Histopathology. 2019;74(6):917-924.