Feasibility of HER2 radionuclide imaging for stratification of BREAST CANCER patients for HER2 directed antibody-drug conjugate therapy

20-25% of all breast cancers are identified as being HER2-positve by the detection of HER2 overexpression using immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH), which is the only validated predictive biomarker to guide treatment stratification of breast cancer patients towards HER2-directed therapies. HER2-directed therapies e.g. trastuzumab (Herceptin), pertuzumab (Perjeta) and T-DM1 (Kadcyla) have contributed to significant improvements in survival outcomes in this patient group. A key challenge with the clinical utility of these treatments is the development of resistance which is evident in the management of patients with metastatic HER2 positive breast cancer.

Tissue based “omics”, combined with the development of molecular imaging agents to detect the degree of HER2 expression in breast cancer patients could offer the potential to tackle this hurdle and decrease dependence on tumour-tissue biopsies which are required to detect HER2 expression by IHC and/or FISH and guide treatment decisions. Tissue biopsies are inherently invasive and at times technically difficult to perform. The real-time imaging of HER2 expression could allow for a non-invasive means to visualise HER2 expression in the entirety of the tumour burden, guide treatment decisions and potentially detect the development of resistance against HER2-directed therapies.

Professor Tony Ng’s group at King’s College London, has been collaborating with other groups in the development of an imaging strategy utilizing molecular imaging radionuclide probes to detect HER2 expression in tumour deposits from HER2-positive breast cancer, e.g. G3 anti-HER2 DARPin. The NCITA exemplar 6 study will encompass a collaborative effort between two NCITA centres, King’s College (KCL) and Imperial College London (ICL), led by Professor Tony Ng and Dr Gargi Patel at KCL and Professor Eric Aboagye and Dr Laura Kenny at ICL.

The Exemplar 6 study (HERPET Trial 
ClinicalTrials.gov identifier: NCT03827317) will evaluate the utility of HER2 radionuclide imaging in the oncological management of patients with metastatic HER2 positive breast cancer while receiving treatment with the antibody-drug conjugate, T-DM1. The study will explore translational end points to develop predictive biomarkers indicative of resistance mechanisms, to facilitate evidence guided decision-making in the clinical management of patients with HER2-positve breast cancer. The NCITA QA/QC unit will also develop standardised protocols for cross-institutional site development of HER2 radionuclide imaging for breast cancer patients.

Study Collaborators: Dr Gargi Patel (KCL), Professor Eric Aboagye (Imperial College London (ICL)), Dr Laura Kenny (ICL)

To find out more, see the
Cancer Research UK HERPET study website.

Radionuclide imaging of human epidermal growth factor receptor 2 (HER2) expression (Image A, arrow) in a mouse model inoculated with HER2-positive human breast tumour (BT474) using radiolabelled DARPin [99mTc(CO)3]+-G3 DARPin-His6. Image B demonstrates the lack of HER2 expression in a mouse model inoculated with a HER2-negative human breast tumour (MDA-MB-468). This biomarker imaging-driven detection of HER2 expression will facilitate the stratification and monitoring of patients on HER2 targeted therapies.