Breast cancer progression is dependent on the formation of new blood vessels that not only help the tumor by supplying additional nutrients, but also allow cancer cells to spread from the breast to distant sites in the body. Several studies suggest a positive correlation between new vessel formation and estrogens. Estrogenic environmental chemicals such as PCBs have been shown to increase the expression of factors known to promote vessel formation in breast tumors. These studies highlight a growing concern that women exposed to estrogenic environmental compounds may be more susceptible to either aggressive metastatic tumors or a high recurrence of breast cancer. Our concept offers a fundamental new understanding of the way the environment contributes to breast cancer progression. This review will be focused on a highly novel Pyk2 signaling complex as a target for therapy of estrogen dependent breast tumor angiogenesis. A better understanding of the role of Pyk2 signaling in estrogen dependent tumor vascularization may lead to the development of a new therapy against aggressive breast cancer using small molecule inhibitors of Pyk2.