Fig. 3: HER3 expression and spatial mapping at BL and association with treatment response.

a, Box plot showing the proportion of HER3 1+, 2+ and 3+ TCs at BL and best overall treatment response. b, Kaplan–Meier estimates of PFS according to HER3-membrane 2+ and 3+ ≥50% of TCs (left) and according to HER3-membrane 1+, 2+ and 3+ in ≥75% of TCs (right) (for both n = 72 and no. of events = 46). c, Clusters of HER3 or neighborhood cell distribution. Digitized DAB-stained slides were overlapped with digitized H&E-stained slides. These regions were then segmented into eight different clusters. Box plots show the proportion of each cluster in 63 evaluable patients, according to treatment response: responders (CR, PR) and nonresponders (SD, PD). The box center lines, box ranges, whiskers and dots indicate the medians, quartiles, 1.5× the IQR and outliers, respectively. Our analysis revealed an association between treatment response and the percentage of cluster 0 (P = 0.040), with an odds ratio of 1.527 95% CI [1.020–2.287]. For all these analyses, using R v.4.1.2, we applied Dirichlet’s regression to identify which clusters were significantly associated with the objective response to treatment (statistical significance was assessed using Wald’s test based on Dirichlet-distributed parameters; the reported P values were unadjusted for multiple comparisons). d, H&E-stained slide showing the composition of cluster 0, characterized by a moderate number of TCs, surrounded by connective areas, with a few immune cells and no necrotic areas. e, Proportion of the different cell phenotypes (epithelial, connective, inflammatory, necrotic and neoplastic areas) across the identified clusters (n = 63). The box center lines, box ranges, whiskers and dots indicate the medians, quartiles, 1.5× the IQR and outliers, respectively.