A major challenge in modern breast cancer treatment is to unravel the effect of drug activity through the systematic rewiring of cellular networks over time. Here, we illustrate the efficacy and discriminative power of our integrative approach in detecting modules that represent the regulatory effect of tamoxifen, widely used in anti-estrogen treatment, on transcriptome and proteome and serve as dynamic sub-network signatures. Initially, composite networks, after integrating protein interaction and time series gene expression data between two conditions (estradiol and estradiol plus tamoxifen), were constructed. Further, the Detect Module from Seed Protein (DMSP) algorithm elaborated on the graphs and constructed modules, with specific 'seed' proteins used as starting points. Our findings provide evidence about the way drugs perturb and rewire the high-order organization of interactome in time.