Overview
The importance of research on breast cancer and the environment
Historical data, migrant studies, twin studies, and geographic patterns of breast cancer incidence around the world suggest that environmental factors play an important role in the etiology of breast cancer. In the United States, an increase in the incidence of breast cancer since the 1940s remains unexplained, and cannot be accounted for by increased detection or changing distributions of known risk factors. Various hypotheses have been advanced to explain these data, including aspects of modern lifestyle, pollution, and infectious agents. One would assume in the face of such a wealth of descriptive data that the environment and breast cancer would be a major focus of epidemiologic research. This has not been the case. Most epidemiologic studies of breast cancer focus on a narrow range of behaviors, such as smoking and alcohol, and ignore a broader spectrum of potential environmental risk factors. Recently, the focus of etiologic research has narrowed even further with an emphasis on breast cancer genetics, and investigators often ignore environmental exposures that interact with genes. The strongest rationale for studying environmental exposures is that many are preventable. Intervening on the basis of modifiable environmental exposures may offer our only hope for reducing the burden of breast cancer.
Benefits and limitations of genetic research
Research in breast cancer genetics has yielded important information. Patterns of somatic genetic alteration and gene expression identify subtypes of breast cancer that appear to respond differently to chemotherapy, radiation, and other forms of treatment. These findings may revolutionize how we treat breast cancer. However, few attempts have been made to link patterns of somatic genetic alteration to etiology, to use information about what genes are mutated in breast tumors to identify the underlying causes of breast cancer. Cloning of the BRCA1 and BRCA2 genes was a tremendous advance, but so far, genetic testing benefits only a minority of patients with a strong family history. In the past five years, more common genetic polymorphisms, including single nucleotide polymorphisms, moved to the forefront of breast cancer research. Common genetic polymorphisms modulate response to diet, hormones, DNA damaging agents, oxidative stress, and other environmental factors. However, the majority of epidemiologic studies that incorporate these common genetic markers ignore the environment and assume that genes act alone.
Integrating genetic and environmental research
Whole-genome association studies are planned that aim to build comprehensive multigene models for breast cancer. Such studies take full advantage of the wealth of information provided by the human genome. The goal is to identify each of the 30–40 inherited genetic variants that, in different combinations, act to determine a woman's risk of breast cancer. But these multi-gene models ignore environmental exposures, as well as interactions between genes and environment. In a very real sense, we may be missing the boat. Over sixty years of descriptive data tell us we need to look carefully at the environment, especially in areas where lifestyles and exposure histories vary across population subgroups. We need to make our investigations of environmental risk factors and breast cancer as far-reaching, comprehensive, and ambitious as studies of breast cancer genetics. In the age of discovery science, huge databases, and data mining, there is no reason that a net should be cast only for genes. Just as breast cancer genetics is now studied at many levels, including somatic alterations and inherited genetic variation, so the environment can be studied at many levels by evaluating individual and group level exposure to a wide variety of potential risk factors. Once we integrate comprehensive knowledge of genetics and environmental factors, we will have a much stronger handle on the causes of breast cancer. In areas such as California where environmental databases already exist and mechanisms exist for collecting additional data, studies of the environment can actually be done more quickly and cheaply than studies of genetics.
Proposal for a comprehensive investigation of breast cancer and the environment lead by the CBCRP
The California Breast Cancer Research Program is in an ideal position to sponsor the first truly comprehensive research program aimed at studying breast cancer and the environment. The following document reviews environmental influences and breast cancer risk, identifies resources in the State of California that could be used to study the environment and breast cancer, and lists specific controversies and topics that could be topics for grants awarded by the CBCRP. A series of recommendations are made for future research. This list is not meant to be all-inclusive, but rather to provide examples of the types of studies that could be done. The advantages of a comprehensive approach to breast cancer and the environment sponsored by the CBCRP are that evaluation and funding would be regionally focused, would build on existing databases and research collaborations, and would capitalize on the rich diversity of the California population. With such a program, the CBCRP could make a major contribution toward addressing the many unanswered questions regarding breast cancer and the environment, and thereby have a huge impact on breast cancer research both within the state and beyond.
