HER2: Expressing potential beyond breast cancer

HER2, also known as Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2), 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.

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

New strategies for direct and indirect oncogene targeting are impacting the ways we diagnose and treat cancer, increasing personalised 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.

Now, HER2 is again playing a central role in elevating the approach to breast cancer diagnosis and care. A new HER2-targeted drug was recently approved in certain geographies to treat a subpopulation of breast cancer patients who express lower levels of HER2 than would have previously qualified them for personalised therapy. At the same time, diagnostic innovation produced a new method for pathologists to determine a patient’s HER2 status that classifies lower expressors of the HER2 protein as “HER2-low” – making it possible to identify those patients eligible for and most likely to respond to this new therapy. These ongoing advancements are bringing about an exciting mindset shift in the oncology community toward the non-binary potential of the HER2 biomarker and new tools for treating breast cancer.

• 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 the potential to lead to successful clinical care and 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 the potential of life-changing therapies.