Etiology and Prevention
Although our foundation of knowledge for the basic science aspects of breast cancer (tumor biology) has expanded greatly over the past decade, there still remains a gap in our strategies for large-scale prevention due to uncertainties over the underlying causes of the disease and their relative importance. There is an extensive list of factors associated with increased or decreased risk for breast cancer. However, some of these factors (such as exposure to light at night) remain controversial; how others affect breast cancer (such as socioeconomic status) remains a mystery, and true causes are yet to be discovered.
The two research topics represented in this section are:
- Etiology: The Role of the Environment and Lifestyle
- Prevention and Risk Reduction: Ending the Danger of Breast Cancer
Research Concluded in 2010
Exploring Disparities, Environmental Risk Factors in Teachers
Breast cancer is more common in urban and industrial areas than in rural areas, fueling speculation that environmental pollutants may play a causal role in its development. Peggy Reynolds, Ph.D., and Susan Hurley, M.P.H., at the Cancer Prevention Institute of California, in Berkeley, and their team of researchers worked with a CBCRP-appointed Scientific Advisory Committee to determine how questions related to environmental risk factors could be integrated into the California Teachers Study, a large on-going breast cancer study. This work resulted in a detailed research proposal funded by CBCRP to investigate the risk of breast cancer associated with both older and newer persistent organic pollutants of human health concern, including polybrominated diphenyl ethers (PBDEs) and their replacement brominated flame retardants, polychlorinated biphenyls (PCBs), , and some organochlorine pesticides (e.g., DDT). This research will look for disparities in, and predictors of, body burden levels of these compounds and explore potentially important windows of susceptibility—times in a woman’s life when exposure may be especially significant. This study offers an important opportunity to investigate how exposure to flame retardants and other persistent organic pollutants impacts breast cancer risk in different racial and ethnic groups.
Mammary Gland Evaluation and Risk Assessment
Human studies suggest that conditions that affect the hormonal environment of the developing fetus may affect breast cancer risk in adulthood. These findings support the hypothesis that fetal exposure to chemicals that affect hormone systems can also affect breast cancer risk. Because the effects of fetal exposures to these chemicals are difficult to study in humans, they are typically studied in animals. However, this area of research is new, and many questions remain about how to evaluate changes in an animal mammary gland structure that occur due to chemical exposure, and how to link findings in animals to potential breast cancer risk in humans. To advance this area of research, Lawrence Kushi, Sc.D., at the Kaiser Foundation Research Institute, in Oakland, and colleagues, held a Mammary Gland Evaluation and Risk Assessment Workshop in Oakland in November 2009 that focused on developing a standard protocol for evaluating mammary gland morphology and chemical risk assessment. This protocol is necessary to advance our understanding of the impact early life exposure to chemicals that affect hormone systems can have on mammary gland development and susceptibility to cancer. It will also provide the scientific basis public policy experts need to develop and implement regulations that limit chemical exposures that are associated with breast cancer.
Circuit Training to Lower Breast Cancer Risk in Latina Teens
Obesity is rapidly rising in children, especially among Latinos. Girls who are overweight often start their menstrual cycles early in life and have an increased frequency of ovulatory cycles, which has been widely linked with increased post-menoapusal breast cancer risk. It is not known whether an exercise intervention can decrease breast cancer risk factors in youth, especially in a high-risk overweight minority population. Jaimie Davis, Ph.D., at the University of Southern California, in Los Angeles, is investigating whether a 16-week circuit training (aerobic and strength training) program can impact breast cancer risk factors, such as age of menarche, frequency of ovulatory cycles, obesity, and insulin resistance in overweight, adolescent Latinas. This is one of the first studies to assess whether a physical activity intervention, particularly a circuit training approach, can lower breast cancer risk in youth. It also is one of the first studies to examine the relationship of physical activity, fat distribution (i.e., fat around the abdominal organs) and insulin resistance on breast cancer biomarkers in youth. This research will expand our understanding of the feasibility of introducing exercise interventions to adolescent girls that may decrease their breast cancer risk as adults.
Grapefruit, Hormones, and Postmenopausal Breast Cancer Risk
Scientists have shown that grapefruit juice can interact with many prescription drugs, including estrogen and progesterone. Researchers have also found that postmenopausal women who consume very modest amounts of grapefruit have higher estrogen levels. Since estrogen is a well-established risk factor for breast cancer, it is biologically plausible that regular intake of grapefruit might increase breast cancer risk. To further investigate this interaction, Kristine Monroe, Ph.D., and colleagues at the University of Southern California, in Los Angeles, studied the effects that consumption of different grapefruit products has on endogenous hormone levels in healthy, postmenopausal women. In their first analyses, Dr. Monroe and her colleagues found considerable inter-individual variability between baseline hormone values and the hormone values seen while consuming grapefruit. Additional analyses are now underway. Findings from this research will help determine whether grapefruit consumption may be a breast cancer risk factor in postmenopausal women. This grant was supported in part by a grant from the California Community Foundation.
Folate, DNA Methylation, and Breast Cancer Metastasis
Folate is a B vitamin that is essential for making DNA and controlling gene expression. Both normal cells and cancer cells need folate for these purposes. DNA undergoes a chemical modification, called methylation, which regulates the expression of genes. The methyl groups available for DNA methylation are manufactured by folate. In 1998, the U.S. government mandated that cereals and grains be fortified with folate (folic acid) to reduce the number of birth defects. It is not known if the high levels of folate people are now consuming could have negative consequences, such as causing cancers to grow or spread more quickly. Teresa Marple, Ph.D., at the University of California, Davis, initiated an investigation into how dietary intake of folic acid affects breast tumor metastasis. She resigned the project prior to completion.
FGFR2 Signaling in human Breast Cancer Cells
FGFR2 is a receptor tyrosine kinase belonging to the fibroblast growth factor receptor (FGFR) family. Recently, two large studies independently suggested that FGFR2 might play a role in postmenopausal invasive breast cancer. Daniel Donoghue, Ph.D., and colleagues at the University of California, San Diego, investigated whether the single nucleotide polymorphisms (SNPs) within Intron 2 of FGFR2 that were identified in these studies alter FGFR2 expression in an estradiol-dependent manner. Dr. Donoghue’s studies demonstrated qualitative changes in FGFR2 expression in response to estradiol and FGF, suggesting future avenues of research. These findings have the potential to open up a new line of study for breast cancer, since there is currently no published data confirming estradiol-dependent FGFR2 expression and any disease-associated polymorphisms. Findings from this research were published in Cell Cycle 8(2009)66.
Research Initiated in 2010
Light at Night and Breast Cancer Risk in California Teachers
Peggy Reynolds
Cancer Prevention Institute of California
Partnership to Advance Breast Cancer Research
Tracey Woodruff
University of California, San Francisco
Persistent Organic Pollutants & Breast Cancer Risk
Peggy Reynolds
Cancer Prevention Institute of California
Vitamin D and Breast Cancer Survival
Wei Wang
Cancer Prevention Institute of California
Research in Progress
Antidepressant and Breast Cancer Drug Interactions
Reina Haque
Kaiser Foundation Research Institute
Breast Cancer Risk Reduction: A Patient-Doctor Intervention
Celia Kaplan
University of California, San Francisco
Breast Cancer Risks in California Nail Salon Workers
Peggy Reynolds and Linda Okahara
Northern California Cancer Center and Asian Health Services
Cancer Mapping: Making Spatial Models Work for Communities
Eric Roberts
Public Health Institute
Environmental Causes of Breast Cancer Across Generations
Barbara Cohn
Public Health Institute
Genes in Hormone Metabolism Pathway and Breast Cancer
Eunjung Lee
University of Southern California
Model-building with Complex, High-dimensional Exposures
David Nelson
Northern California Cancer Center
New Paradigm of Breast Cancer Causation and Prevention
Robert Hiatt
University of California, San Francisco
Pesticide and Gene Interactions in Latina Farm Workers
Paul Mills
University of California, San Francisco
Prognostic Implications of DNA Glycation in Breast Cancer
Daniel Tamae
Beckman Research Institute of the City of Hope
Anna Wu
University of Southern California
