A focus of much cancer research is at the molecular and cellular levels. In contrast, the effects of social interactions and psychological state are less investigated, and considered by many a "soft" science. Yet several highly rigorous studies have begun to tease out biochemical pathways by which the brain can influence the development and growth of cancer. Previous reviews have discussed the concept of stress and cancer. Here, we discuss recent work showing environments that are more complex and challenging, but not stressful per se, and that have robust effects on peripheral cancer by activating a specific neuroendocrine brain-adipocyte axis. These enriched environments lead to activation of the sympathetic innervation of fat tissue, suppression of leptin, and a reduction in cancer proliferation by inducing hypothalamic BDNF expression. We summarize this work and discuss how these data integrate into the body of literature regarding stress, the environment, and cancer.