Summary
A Danish nationwide screening effort found conventional HER2-positive status in 62 of 806 people with esophageal squamous cell carcinoma. In a small phase II trial, trastuzumab-based treatment showed responses, while tissue mapping found HER2-poor fibrotic areas enriched for B7-H3.
A nationwide Danish screening effort identified conventional HER2-positive status in 62 of 806 people with esophageal squamous cell carcinoma (ESCC), or 7.7%, according to a medRxiv preprint. The researchers also reported results from a phase II trial of trastuzumab-based chemoimmunotherapy and used spatial protein analysis to examine how HER2 varied within tumour tissue.
HER2 is a cell-surface protein that can help drive cancer growth; trastuzumab is an antibody that targets it. HER2-directed treatment is not established for ESCC, the researchers note, making the findings an early test of whether this biomarker can identify patients for such therapy.
Early results from the phase II trial
Fifteen patients entered the trial before it closed prematurely. The primary endpoint was the proportion of patients alive without disease progression at six months: this was 46.7% (95% confidence interval, 21.3–73.4%). Among the 11 patients with measurable disease, six had a partial response. Grade 3 or higher adverse events occurred in 13 of the 15 patients.
These are results from a small phase II study, and the abstract reports no comparison group. The figures therefore describe outcomes in the treated group rather than a measured advantage over another treatment. The confidence interval around the six-month progression-free survival estimate is broad, reflecting the limited number of patients. The trial’s premature closure also left the treatment assessment based on only 15 participants.
Mapping HER2 across tumour tissue
The researchers analysed 638 spatial tissue tiles from eight patients using Deep Visual Proteomics, an approach that measures proteins in selected regions of tissue. HER2 was detected in 48.7% of the tiles. Detection was lower in fibrotic microenvironments, with an adjusted odds ratio of 0.10. The analysis also found B7-H3 enriched in HER2-poor fibrotic regions, with an adjusted odds ratio of 7.10.
The tissue results point to variation within tumours: a sample’s overall HER2 status may not describe every local region. B7-H3 is a candidate complementary target identified by the spatial analysis, not a treatment tested in this trial. The findings could help guide further studies of how tumour surroundings affect target selection.
The report is a preprint, so its results have not yet completed peer review. Together, the screening, trial and tissue-mapping findings provide an initial account of HER2 testing and targeted-treatment research in ESCC, rather than establishing a standard of care.