FIGURE 1.

Bioinformatic identification and experimental validation of RTKs mediating trastuzumab resistance. A, forest plot of the concordance index estimates of survival risk for each RTK in HER2 patients. Data are ordered and presented as the mean ± S.E. Higher concordance index numbers predict worse outcome. The most significant p values are also shown; *, p < 0.05; **, p < 0.01; ***, p < 0.001. B–D, SKBR3, BT474, or AU565 breast cancer cells engineered to stably express the indicated RTKs were cultured for 2 days in increasing amounts of lapatinib, and then cell viability was measured and plotted as a function of drug concentration. Error bars, S.E. Results are summarized in E. NR, no rescue; P, partial rescue; R, rescue. F–H, Kaplan-Meier curves of IGF1R, TYRO3, and PDGFRb in each of the HER2 molecular subtype. Gene expression is split on the median into low and high classifications, and data are presented as the probability of relapse-free survival or distant metastasis-free survival versus time in months.