Innovative fiber optic–based approach of HER2 expression quantitative assessment using inPROBE technology.
Authors: Stencel Dariusz M. , Staniszewski Marcin , Polkowski Wojciech , Kurylcio Andrzej , Kopyto Przemysław , Staniszewska Magdalena 
Published: October 2024

e13023

Background:
The current standard of HER2 expression assessment on cancer cells (breast cancer, gastric cancer) is IHC/FISH. The results are semi-quantitative and could be imprecise or false in pts. with HER2-low expression. New quantitative methods are desired to allow for accurate HER2 determination and providing personalized treatments.
Methods:
We developed an innovative tool for quantitative assessment of HER2 expression on cancer cells. inPROBE is a real-time,
in vivo
diagnostics, merging molecular biology with photonics technology. The probe inserted into breast tissue is an optical fiber combined with monoclonal antibodies specifically directed against HER2 that allows for
in vivo
linking the biomarker. Then the probe is placed in a dedicated device which, after mathematically calculating the change in light spectrum, provides accurate numerical values of the HER2 concentration. To determine the correlation of HER2 levels detected with diagnostic probe relative to receptor status as determined by IHC/FISH we conducted an interventional, open-label, multicenter, single-arm safety and efficacy clinical trial in female patients aged 18 to 75 years with breast cancer (BC) prior to tumor surgical resection and known HER2 status. The concentration of the HER2 receptor was measured using a diagnostic microprobe inserted in the tumor under US guidance. To assess the optimal puncture site the second probe examination was performed at the same time in the immediate tumor vicinity (up to app. 1 cm from tumor border).
Results:
Among 22 women with a histopathologically confirmed BC and known HER2 status, 18 were included in statistical analysis (6 pts. with HER2-positive and 12 pts. with HER2-negative BC), while 2 of 22 patients were early terminated, and 2 did not meet eligibility criteria. Mean (SD) age was 56.6 (±10.6) years, range 39–77 years. Mean (SD) BMI was 27.6 (±6.0), range 20–42 kg/m
2
. ECOG PS was 0. The study met its primary endpoint, i.e. the HER2 receptor concentration ranges detected with microprobe corresponding to HER2 receptor status identified by IHC/FISH have been determined (mean, median, max and min values). For minimum values the difference was significant with use of Wilcoxon exact test (significantly lower values for HER2-negative than for HER2-positive BC, p=0.041). For the remaining comparisons the analysis detected reasonable numerical tendency toward higher values in HER2-positive group as compared to HER2-negative. The correlation of HER2 receptor concentrations detected with the microprobe inserted within the tumor and in the near tumor area in overall population showed, that mean values differed with significant positive correlation of moderate magnitude, p=0,046. Safety profile of device was good and promising. No adverse events were observed.
Conclusions:
Further clinical development of inPROBE can be continued with no risks for patients’ safety.
Clinical trial information: NCT05415943
.