Enhancing Imaging and Therapy of HER2-low Breast Cancer – EITHER2BC

Breast cancer is the most prevalent cancer in the world. Female breast tumours alone account for approximatively 11.7% of new cancer cases each year, with more than two million women diagnosed in 2020, which highlights this disease as a major public health concern. At the molecular level, this malignancy is a very heterogeneous disease that could be divided into five subtypes (Luminal A-like, Luminal B-like HER2 negative, Luminal B-like HER2 positive, HER2-enriched, triple negative breast cancer) according to the immunohistochemistry expression of estrogen receptors, progesterone receptors and human epidermal growth factor receptor 2 (HER2). About 20% of newly diagnosed cases of breast cancer are HER2-positive and the prognosis of this subtype improved with the implementation of HER2-targeted therapy using monoclonal antibodies. Despite this notable progress, a high percentage of patients (40–50%) displays a low expression of HER2 (HER2-low) that does not allow the effective use of anti-HER2 therapies. However, recent studies reported that HER2-low patients might benefit from novel HER2-targeted therapies based on antibody-drug conjugates (ADC). In addition, a phenomenon of resistance to those HER2-targeted therapies has been reported. Besides, the accurate determination of HER2 status is critical to identify patients who could benefit from these therapies, mainly when, the current gold standard assays in the determination of HER2-low/HER2-negative expression, have been challenged due to their low accuracy. These findings led us to hypothesize that targeting HER2 in a context of HER-low breast cancer patients based on nuclear medicine strategies (i.e. companion diagnostics, theranostics and radioimmunotherapy, RIT) might represent an innovative “image and treat” approach by combining non-invasive whole body molecular imaging (e.g. SPECT, PET) and new targeted therapies (e.g. RIT, ADC) to overcome present-day issues.