New Paradigm of Breast Cancer Causation & Prevention-Phase 2

Institution: University of California, San Francisco
Investigator(s): Robert Hiatt, M.D., Ph.D. -
Award Cycle: 2014 (Cycle 20) Grant #: 20ZB-8303 Award: $811,840
Award Type: SRI Program Directed Awards
Research Priorities
Etiology and Prevention>Prevention and Risk Reduction: ending the danger of breast cancer

Initial Award Abstract (2015)

There is no one cause of breast cancer. Causes of breast cancer are actually multiple and include genetic, other biological, behavioral, environmental and social factors, all of which can interact and influence each other at various critical stages of life. Traditional studies that have tended to focus on one factor at a time, while trying to control or adjust for other factors and have given us much information. But the larger picture cannot be taken into account by these traditional methods. Our research uses a modeling approach to illustrate the complexity of the causes of breast cancer, first, to highlight the many different types of interacting influences that come into play, and, second, to estimate mathematically the impact of changes in various key factors that might be the target of prevention programs. In the first phase of this research we developed a model of postmenopausal breast cancer, the most common variety. Now in Phase II we plan to extend this model to include up-to-date evidence from new studies, to include premenopausal as well as postmenopausal breast cancer and to try to estimate the impact of some factors, mainly environmental chemicals, where data is lacking from human studies, but where animal experiments may be enlightening. We plan to disseminate this information, not only in scientific presentations and publications but also through the media and a website version that is accessible and understandable to the lay public.

The question(s) or central hypotheses of the research: This research does not attempt to answer one specific question. Rather it seeks to illustrate breast cancer causation in general as a complex ecologic system with multiple factors influencing breast cancer occurrence at different levels of activity from the genetic and biologic to the social and physical environment. We have previously developed a new model to demonstrate this perspective, which has been published in the peerreviewed scientific literature. Simultaneously we have worked with graphic designers to create web-based visual representation of this model that can be used by the lay public and other interested parties.

In the current project we propose to extend this work in three ways: First, we will develop a more systematic and transparent approach to reviewing the existing evidence and review the literature for the most up-to-date information to include. Second, we will modify the model to include premenopausal breast cancer that has some different risk factors than postmenopausal cancer. Third, and finally, we will seek to include evidence from animal experiments that in many cases provide evidence unavailable from human studies. The combination of human epidemiologic and animal experimental data is especially innovative and a novel approach to using all the science available to explain breast cancer causation and suggest avenues for prevention.

The general methodology: Our approach is to use a team of experts in multiple subject areas to create two types of new models. The disciplines represented by the experts we have assembled include breast cancer epidemiology, human and animal toxicology, environmental health, health evaluation and intervention research, health policy, advocacy, risk assessment and modeling expertise. We will meet with this team six times over two years to review both the human and animal literature, discuss problems and decide on solutions and work to produce both a new large Conceptual Model and a smaller but still substantial Mathematical Model to show the effect of prevention measures at the population level.

Innovative elements of the project: Our project is innovative in modeling breast cancer etiology as a complex system, in taking a transdisciplinary approach that includes the knowledge and judgment from a wide range of scientists and in, for the first time, including both human epidemiologic and animal experimental data in the model development.

Progress Report 1 (2016)

Breast cancer has multiple causes that include biological, behavioral, social, and environmental factors, all of which can interact and influence each other at various life stages. We are using a modeling approach to illustrate the complexity and the interactivity of different factors and to estimate mathematically the impact of changes in various factors that could be targeted for prevention programs.

In our first phase, we focused on post-menopausal breast cancer and in our current project, Phase II, we will expand the model to include pre-menopausal breast cancer and evidence from newly published studies and to estimate the impact of changes on factors, primarily environmental chemicals, where data on human studies is lacking by bringing in results from animal studies. Our results will be disseminated through scientific publication and visually on a website thatís accessible and understandable to the lay public.

Our project is progressing as planned. We have held three meetings with our experts in the first year and will have three more meetings in the coming year, with the first one of those already scheduled. With the input of our experts and after extensive discusssions, we have determined the best type of model to use. Between meetings, our investigators have done extensive literature reviews and have gathered statistics necessary to test our model. Our programmers have developed a first iteration simplistic model to test our assumptions, which will be reviewed by our experts at our next meeting in March.

In the next year, we will continue to meet with our experts (3 times) to get their input, discuss programs, and evaluate our progress and will test and finalize the model.