Figure 1

Effect of estrogen receptor distribution on molecular subtype assignments. The University of North Carolina (UNC) cohort is the PAM50 training cohort. Only samples with available prototypic tumor subtypes and available estrogen receptor (ER) status are shown (n = 118). In each horizontal strip, the vertical bands represent individual patients and are arranged in the same sequence for each horizontal band. First, we considered the UNC cohort, where there was a balanced ER-positive to ER-negative distribution—46% ER-positive (54/118) and 54% ER-negative (64/118)—represented by the shaded pie chart labeled “UNC cohort.” In the first strip at the top, labeled “ER status”, the ER status on the UNC cohort is depicted as dark vs. light gray, representing ER-positive vs. ER-negative cases, respectively. In the second strip, labeled “Original subtype assignment,” the original subtype assignments on the UNC cohort are shown. Next, we considered a subset of the UNC cohort (n = 75), which we created by sampling ER-positive and ER-negative cases disproportionally, with 15% ER-positive (11/75) and 85% ER-negative (64/75), as represented by the pie chart labeled “UNC subset.” In the third strip, labeled “Standard gene centering,” assigned subtypes by standard gene centering on the subset of the UNC subset, where ER is disproportionally distributed, are shown. The misclassification rate is 33.3% (25/75) compared with the first 75 bands in the second strip. In the bottom strip, labeled “Subgroup-specific gene centering,” assigned subtypes by the proposed subgroup-specific gene centering on the subset of the UNC cohort, where ER is disproportionally distributed, are shown. The misclassification rate is 5.3% (4/75). Here the classification is similar to the actual classification, shown in the first 75 cases of the second strip, labeled “Original subtype assignment.” Her2, Human epidermal growth factor receptor 2; LumA, Luminal A; LumB, Luminal B.