Posted on Oct 14, 2022

If you’re in the breast cancer world, then you’ve undoubtably been following the exciting developments in the treatment of HER2-low breast cancers. Presented at ASCO 2022 and published in the New England of Journal of Medicine, results of a phase III trial of the drug Enhertu have shown to improve overall and progression free survival for this population of metastatic breast cancer patients.

Lead author Dr Shanu Modi predicts that the drug will have an “impact on survival for approximately 50 per cent of patients diagnosed with metastatic breast cancer today.” News met with a standing ovation from the ASCO audience.

At Cerca Biotech, we’re leading the applause: as Mammatyper® enables a more accurate quantitation of the HER2-low subtype, through RT-qPCR technology, now found in most labs.

The role of HER2 in breast cancer diagnosis and treatment

HER2 or human epidermal growth factor receptor 2 is a protein receptor involved in normal cell signalling, but overexpression leads to in uncontrolled cell replication: occurring in around 15%-20% of breast cancers. These are known as HER2-positive breast cancers. Unfortunately, the sub-type is characterized by a worse prognosis and more aggressive disease.

The development of trastuzumab (Herceptin®) in the late 1990s was a game-changer for treatment of HER2-positive breast cancer. Herceptin and other trastuzumab-based regimens have had a huge impact on HER2-positive disease, with cure rates of over 90% for those with early-stage cancer, and median survival in metastatic disease now reported of over 57 months.

For patients with HER2-low tumours, the outlook has been historically less positive. Approximately 60% of HER2-negative metastatic breast cancers express low levels of HER2. These are the HER2‑low tumours: including hormone receptor-positive (HR+) and hormone receptor-negative (HR-) cancers (which includes the difficult to treat ‘triple-negative’ breast cancer cohort) that vary in prognosis and treatment response.  

The current binary and oversimplified approach to breast cancer treatment only splits patients into two groups. HER2‑low breast cancer is treated as HER2-negative. These patients have limited targeted treatment options if their cancer progresses after initial therapy: often their only choice being palliative chemotherapy.

DESTINY-Breast04 trial

This cohort of breast cancer patients were in desperate need of therapy alternatives: the DESTINY-Breast04 trial has brought them just that. The first randomized study to test an antibody-drug conjugate, called Enhertu (trastuzumab deruxtecan or T-DXd). Antibody-drug conjugates are targeted medicines that deliver chemotherapy agents directly to cancer cells.

Dr Shanu Modi of Memorial Sloan Kettering Cancer Centre and colleagues investigated Enhertu versus standard, single-agent chemotherapy. The findings were overwhelming positive: HER2 targeted therapy produces statistically significant and clinically meaningful progression-free survival and overall survival for patients with HER2-low metastatic breast cancer. Meaning expanded therapy to a new population of patients and the establishment of a new standard of care.

557 patients were involved in the trial with global enrolment across three continents, for those randomised to the Enhertu group there was a gain in survival of 6.6 months and ‘vast majority’ of patients with low HER-2 had tumour regressions. Creating hope and precious extra time for patients with previously limited options. In the words of Dr Modi herself, “we anticipate these results to be practice changing.”

Improving accurate detection of low HER-2 breast cancers

There is now a need to bring diagnostic procedures in line with practice changing progress in oncological therapy.

How can we differentiate those patients with sufficient levels of HER2 who will be responsive to Enhertu?

Breast cancer patients are routinely tested for HER2 expression using immunohistochemistry (IHC). Yet IHC is fraught with issues including human differences in interpretation. For HER2, ER, and PR, several studies have reported divergences of up to 20%.

MammaTyper® improves the accuracy of subtyping through an easily replicated and quantitative measurement of marker gene expression. The aim is to support pathologists in overcoming limitations of semi-quantitative staining methods.

Quantitative relative gene expression data of the four biomarkers, including HER2, can be generated within six hours. MammaTyper® results show high precision in both intra and inter-run reproducibility. Technical validation of the test resulted in very low inter-site variation. Precise determination of the breast cancer subtype in patients, is key for accurate identification of HER2-low patients who may be suitable for Enhertu (trastuzumab deruxtecan).

“Mammatyper® is not a new tool in the diagnosis of breast cancer, the clinical proof behind this assay goes back to 2015 and before. The use of well-established RT-qPCR technology to directly measure gene mRNA expression status in breast cancer tumours, enables clinicians to better evaluate treatment needs.”

MammaTyper® uses a single machine-read methodology allowing concordance between key reference laboratories, moving, in time, to all mainstream healthcare. Pricing on these kits allows access to genomic diagnosis like never before.

Thanks in part to the post-Covid-19 proliferation of qPCR systems and MammaTyper® protocols, we can help to repurpose these systems to not only reduce the backlog of testing, but to actively improve the result accuracy and reliability.”

Vinicio Tassani, Clinical Director, Cerca Biotech.

Where next for targeted breast cancer therapy?

The results of the DESTINY-Breast04 trial are just the beginning: researchers are already exploring other targeted breast cancer treatments and different uses for Enhertu.

At Cerca Biotech, it’s our mission to help identify all breast cancer patients who can be treated with these new therapies.

Enhertu is now being used in clinical practice in the United States, and we are actively reaching out to US collaborators to evaluate MammaTyper® to stratify patients. Along with several European collaborators in preparation for use of the treatment in different localities.

Will you join us and be part of the movement to precisely identify and treat all breast cancer sub-types and improve survival and quality of life for everyone living with breast cancer?