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Understanding HER2-low breast cancer

August 29, 2022

illustration of patients discussing breast scans with doctors

At the recent 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, the DESTINY-Breast04 trial was a hot topic that received a standing ovation for the breakthrough results presented. Dr. Shanu Modi’s presentation introduced the concept of HER2-low breast cancer, alongside the very exciting results from the trial. This was the first time ever in a clinical trial that results showed that patients with low HER2-expressing metastatic breast cancer benefitted from a targeted therapy known as trastuzumab deruxtecan (T-DXd/Enhertu®).

HER2-low breast cancer represents a minimum of 55% of breast cancers, so being able to apply targeted treatments can help us overcome a major medical and scientific challenge. There is hope this will lead to a new standard of care for HER2-low breast cancer patients. HER2-positive patients also stand to benefit from this treatment.

The term HER2-low breast cancer is still new to many people. Keep reading to better understand what HER2-low breast cancer is and how the results of the DESTINY-Breast04 trial apply to this classification.

What is HER2-low breast cancer?

Under normal circumstances HER2 proteins help control healthy breast cell growth and maintenance, but when breast cells have too high of HER2 levels on surface cells, this can make them grow and divide uncontrollably.

Around 15% to 20% of breast cancer patients are HER2-positive and they are typically more aggressive than other types of breast cancer. HER2-positive breast cancers have historically been defined as meeting a high threshold of HER2 molecules (3+ IHC score). Treatment options for HER2, include targeted therapies like trastuzumab/Herceptin®.

Tumors within the HER2 population that have low levels of HER2 expression are what classifies a patient as having HER2-low breast cancer and until recently have been reported as HER2 Negative on a pathology report. Recent research has shown that even with HER2, receptors can still be targetable.

The Results and Impact of DESTINY-Breast04

So, why is the breast cancer field buzzing with the news of the DESTINY-Breast04 trial results? Essentially, the results show that HER2-low breast cancer is now eligible for targeted treatment via a novel HER2-targeted therapy. It’s believed that more than half of breast cancer patients are HER2-low and the results of this trial opens new treatment options for this large number of patients.

The trial found that patients who previously received treatment for HER2-low metastatic breast cancer with T-DX (which is an antibody-drug conjugate) had significant improvements in survival compared to those treated with chemotherapy. The study found that the risk of disease progression is approximately 50% lower and the risk of death was 36% lower with T-DXd compared to chemotherapy.

This news is extremely promising to patients with advanced, metastatic breast cancer. Especially for patients with cancers that have become resistant to all available treatments to date.

The Future of HER2-Low Research

How the results of the DESTINY-Breast04 trial will be implemented into breast cancer treatment are still somewhat unclear, but more research is underway to discover the effectiveness of HER2-targeted treatments in combination with immunotherapy for patients with advanced HER2-positive breast cancer.

It’s believed that DESTINY-Breast04 trial represents something much larger than just the results of this particular trial. It seems we may be entering a new era of targeted therapies, which ideally will help patients who have become resistant to other treatments have new options for treatment.

Time will tell what the results of the DESTINY-Breast04 trial truly end up meaning for breast cancer patients, but for now these promising results usher in a lot of hope and promise.