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ARTICLE ABSTRACT: There are challenges to the dominant research paradigm in breast cancer science. In the United States, science and social activism create paradigmatic shifts. Using interviews, ethnographic observations, and an extensive review of the literature, we create a three-dimensional model to situate changes in scientific controversy concerning environmental causes of breast cancer. We identify three paradigm challenges posed by activists and some scientists: (1) to move debates about causation upstream to address causes; (2) to shift emphasis from individual to modifiable societal-level factors beyond an individual's control; and (3) to allow direct lay involvement in research, which may raise new questions and change how questions are approached, the methods used, and the standards of proof. We use our model to examine controversies about doing scientific research, interpreting scientific results, and acting on science. Ultimately, we aim to understand what impedes construction of new methodologies and knowledge about environmental factors in human disease.