With the knowledge of the spatiotemporal pattern of metastasis formation in the different cell line derived tumor models of spontaneous metastasis reported here, along with the reported strengths and limitations of the different imaging modalities, we can better plan and perform longitudinal therapeutic response studies leveraging non-invasive assessment of metastatic disease response in the same animals over time in an effort to help advance new anticancer drugs targeted to advanced metastatic disease in both, TN and HER2+ breast cancer. Here, ERBB2 is linked to breast cancer.