Cancer is a complex evolving ecosystem. In the realm of medicine, we define cancer as an ecological phenomenon starting with one rebel cell breaking free from its ecological limits and multiplies rapidly disrupting the equilibrium of resident tissue homeostasis. This will eventually lead to the extinction of other species and potential ecosystem collapse with many unpredicted variations. These ecological changes of tumor microenvironment will apply novel selection pressure on cancer cells and dictates which changes in cancer cells offer adaptive advantages. To address the significance of these evolutionary and ecological processes in cancer regarding cancer initiation, progression, and metastasis, we study how various tumors are evolving in their microenvironment from normal to precancer and cancer in clinically meaningful ways. We study how changes in microenvironment of normal, precancer, and cancer cells can change their phenotype adapting to varied microenvironment and how adaptation to it can shape the new ecosystem and evolutionary trajectory of cancer cells. This interplay between tumor cells and the microenvironment plays a fundamental role in the development of an ever-changing tumor ecosystem leading to more genotypic heterogeneity and phenotypic plasticity. We use the integration of spatial single-cell transcriptomics, proteomics, metabolomic and lipidomics, and pathomics machine learning analysis to capture the heterogeneity and plasticity of cancer cells in their natural ecological microenvironment and habitats. We discovered novel metabolic phenotypic switch in cells adapted to early acidosis in mammary ducts leading to pre-cancer and carcinogenesis. We then used these markers in our breast cancer ductal carcinoma cohort to find biomarkers for progression from precancer to cancer and upstaging of DCIS.