The novel imaging agent gallium (Ga)-68–ABY-025 may help to predict early metabolic response to HER2-targeted treatment in patients with HER2-positive metastatic breast cancer, according to a recent study published by Alhuseinalkhudhur et al in The Journal of Nuclear Medicine. These findings suggested that by providing whole-body quantification of HER2 expression, Ga-68–ABY-025 positron-emission tomography/computed tomography (PET/CT) may play a role in treatment planning and may spare patients from unnecessary drug-related side effects.
Background
Up to 20% of patients with breast cancer have HER2 overexpression, making the protein a therapeutic target for both new and recurring cases. However, since breast cancer is a heterogeneous disease and HER2 expression may vary within the same patient and over time, it may be common for HER2-targeted treatments to be unsuccessful and rare for metastatic disease to be cured.
“While HER2 status can be confirmed by biopsy results in early-stage breast cancer, it is more complicated in advanced disease, where multiple metastases might have a heterogeneous HER2 expression,” explained lead study author Ali Alhuseinalkhudhur, MD, a PhD candidate in the Department of Immunology, Genetics, and Pathology at Uppsala University in Sweden. “Imaging the entire body rather than just the primary cancer site can give physicians a total estimate of HER2 expression, so they can plan targeted therapies appropriately,” he added.
Study Methods and Results
In this study, researchers enrolled 40 patients with known HER2-positive breast cancer—19 of whom had primary breast cancer and 21 of whom had metastatic breast cancer with a median of three previous treatments—and investigated Ga-68–ABY-025 PET as a noninvasive tool for whole-body HER2-receptor quantification.
The researchers performed Ga-68–ABY-025 PET/CT, fluorine (F)-18–fludeoxyglucose (FDG) PET/CT, and core-needle biopsies from targeted lesions at baseline for each patient. F-18–FDG PET/CT was repeated after two cycles of therapy to calculate the directional change in tumor lesion glycolysis. The researchers then measured tracer uptake in up to five of the largest lesions per patient—including the biopsied lesion—and compared standardized uptake values from Ga-68–ABY-025 PET/CT with the biopsied HER2 status and the change in tumor lesion glycolysis.
The researchers discovered that Ga-68–ABY-025 PET/CT successfully enabled quantification of HER2 expression, and uptake correlated significantly with metabolic response among patients, particularly in those with metastatic breast cancer. Further, an inverse association was found between the number of previous treatments and the metabolic response to the current treatment—where the more treatments received, the higher the Ga-68–ABY-025 required to induce a metabolic response.
Conclusions
“The ability of [Ga-68–ABY-025] PET/CT to provide a whole-body visualization of HER2 expression and to predict metabolic response is advantageous and exceeded the biopsy-based approach for [patients with] metastatic breast cancer. HER2-based imaging tools might provide a solution in situations where biopsies cannot be performed safely or when biopsy results are inconsistent. In addition, a PET-based approach to evaluate the appropriateness of targeted therapy might help avoid unnecessary side effects and might provide a more personalized opportunity for timely therapy corrections,” highlighted Dr. Alhuseinalkhudhur. “Our work is a strong example of the development toward personalized medicine. We hope that the value of quantification of biomarkers such as HER2 expression in [patients with] cancer will be appreciated to a larger extent and introduced into nuclear medicine practice for both diagnostic imaging and therapy,” he concluded.
Disclosure: For full disclosures of the study authors, visit jnm.snmjournals.org.
