Clusters relative percentage according to T-DXd sensitivity in cohort 1 (HER2-overexpressing). For each patient, the corresponding HER2 pathology slide ( n = 61) was divided into 64 x 64-px non-overlapping patches that were classified into eight clusters using a Mini-Batch K -means algorithm. The following box plot illustrates the relative percentage of each cluster in each slide and its association with the confirmed objective response or non-response to T-DXd. Box center lines, box ranges, whiskers and dots indicate medians, quartiles, 1.5x IQR and outliers, respectively. Cluster 6 presented a significant association with non-response to T-DXd ( P = 0.011, FDR-adjusted P = 0.086). P values were calculated using the MannWhitney U -test and adjusted for multiple hypothesis testing using the BenjaminiHochberg method. All statistical tests were two-sided.