We study breast cancer in humans as a model for understanding cancer as a system in its entirety and as a life cycle, including cell of origin, transformation, subtype selection, biology and ecology of the primary tumor, the tumor microenvironment, tumor immunology and surveillance, dissemination via the circulating tumor cell, metastasis to the lymph nodes, and metastasis to distant sites. Metastasis is the major cause of death from cancer and patients with breast cancer are at risk of developing one of four major metastases to a distant site, which we argue lymph node metastasis is a precursor to (rather than simply a reflection of): metastasis to the CNS (e.g., the brain), metastasis to the lungs, metastasis to the liver, and metastasis to the skeletal system (bones) (1-5). We recently utilized whole transcriptome technologies to define the full complement of differentially expressed kinases and phosphatases in HER2+ breast cancer: in the primary tumor, and in metastasis to the CNS (6-8). Here we utilize whole transcriptome technologies (9, 10) to measure total transcription in the bone metastases of humans with breast cancer, comparing the bone metastatic transcriptome to the primary tumor transcriptome and to normal cells from the breast. We identify here a therapeutic target based on its optimized therapeutic index: differential expression and up-regulation upon metastasis to the bone, PTPRA, as a candidate therapeutic target for the medical management of bone metastasis.