Fig. 3: Analysis of drug combination effects on tumor growth in a luminal-like breast cancer PDX model using SynergyLMM.

a Schematic representation of the signaling pathway investigated by Gilfillan et al. MAS98.06 is a luminal-like breast cancer PDX model in which tumor growth is promoted by the activity of the estrogen receptor (ER). Fulvestrant acts as an ER antagonist, inhibiting tumor growth. The activation of HER3 by Heregulin, or EGFR by EGF, promotes their dimerization with HER2, inducing tumor growth in an ER-independent manner. Trastuzumab is a monoclonal antibody that targets HER2, inhibiting this pathway. b Tumor growth in Heregulin, EGF, Fulvestrant, and Trastuzumab combination experiments in the breast cancer PDX MAS98.06 model. Each curve corresponds to an individual mouse: control n = 5, Heregulin n = 5, EGF n = 4, Fulvestrant n = 5, Trastuzumab n = 5, Heregulin + Fulvestrant n = 8, EGF + Fulvestrant n = 5, Fulvestrant + Trastuzumab n = 5, Heregulin + Trastuzumab n = 6. c Results of the highest single agent (HSA) synergy evaluation using SynergyLMM, at day 28, based on the experiments shown in (b). The horizontal dashed lines indicate the synergy thresholds of 1 for the combination index and 0 for the synergy score. The error bars indicate the 95% confidence intervals for the combination index and synergy score. The dot in the center indicates the estimated combination index and synergy score values. The dot colors indicate the two-sided (non-adjusted) p value from SynergyLMM. Ctrl Control, Her Heregulin, Fulv Fulvestrant, Trast Trastuzumab. Source data are provided as a Source data file.