Breast Cancer and the Environment Research Program –
Annual Extended Environmental Exposures Conference – November 2014, San Francisco
The Breast Cancer and the Environment Research Program’s (BCERP) annual gathering of scientists and community partners took place in San Francisco, November 19-21. As community partners for BCERP research being conducted at UW-Madison, WBCC Executive Director, Dawn Anderson and Board Member, Kris Miller attended the conference with other community partners, Mary Pat Berry, Sarah Mroz, Dr. Beth Neary and our lead investigator at UW, Michael Gould, PhD.
BCERP is co-funded by the National Institute of Environmental Health Sciences (NIEHS) and the National Cancer Institute (NCI). The research began in 2003 and is now taking place at ten sites across the country. These sites, using both epidemiological and biological studies, are looking at breast cancer risk across the lifespan. Specifically, research is focusing on “Windows of Susceptibility” during a woman’s lifespan, beginning in utero, during which exposures to certain environmental stressors may cause biological changes that increase risk for breast cancer later in life.
It is important to point out that in this context, “environment” is considered any non-inherited factor, including lifestyle and behavioral factors (such as body weight, physical activity and dietary factors), reproductive factors, chemical agents and social factors (such as local government control over chemical use, access to fresh food and health care).
Early puberty has long been established as a risk factor for breast cancer and has been of particular interest to the researchers. We know that puberty is occurring at younger ages than just a few decades ago and there is great interest in why that is so. The initial three sites have been conducting what are known as the Puberty Studies of BCERP. Dr. Susan Teitelbaum of the Mount Sinai School of Medicine (one of the puberty study sites) presented information indicating that environment is related to girls’ development and emphasized the importance of this “enormous wealth of information” in understanding the role environment plays in girls’ development. Over 1200 girls, between the ages of 6-8, have been followed for over ten years during a critical time in their lives. During that time, over 100 biomarkers in blood and urine were measured. Information regarding demographics and ancestry were separated out from information about environmental exposures so that researchers could attempt to make associations between exposures and the timing of when girls began puberty.
Dr. Larry Kushi (Kaiser Permenente) discussed outcomes from research looking at the role of phytoestrogens in pubertal onset. Phytoestrogens are estrogenic compounds found in plants – the most recognizable of which are soy products like tofu or edamame. In his studies, girls who consumed higher quantities of phytoestrogen had a somewhat delayed onset of breast development in comparison to girls who consumed less. Interestingly, no association was found between phytoestrogen intake and the onset of pubic hair, another hallmark of pubertal onset. This suggests that different biological pathways are involved.
Research was also done at the genetic level – exploring associations between when puberty began and variations in biological pathways that play a role in pubertal timing. Dr. Chi-Chen Hong (Roswell Park Cancer Institute) examined several pathways, focusing on metabolic pathways since obesity appears to be associated with early puberty. She reported that for both breast and pubic hair development, obesity, growth and development, and lipid metabolism had the highest number of associations with early puberty. In African American girls, neural pathways were also significant. Dr. Susan Pinney also uncovered a potential association between the degree and timing of DNA methylation with some changes related to puberty.
All of this work around puberty is helping researchers understand the relationship between environment and when a girl enters puberty. If we understand it at the molecular level we can begin to connect the dots and recommend risk reduction strategies that not only may prevent genetic damage at this critical time in a girl’s life, but may also push the puberty window back out to an older age.
While puberty is considered one important “Window of Susceptibility” to environmental damage, there are others. Researchers in the “WOS” arm of the program are conducting biological studies, often using animal models, to evaluate the effects of suspected environmental stressors at different windows in a woman’s lifespan. A second portion of the summit was given over to these researchers to share their work.
Previous animal studies have shown that a high fat diet prior to puberty can increase breast cancer risk, and that even if a low fat diet is adopted in adulthood, the “damage” cannot be undone. Dr. Shuk-Mei Ho (University of Cincinnati) has been looking at the interactive effects of a high fat diet and exposure to the chemical BPA on pregnant rats, specifically the effects on the offspring. Her outcomes showed that exposure to a high fat diet and BPA, even at low doses, resulted in higher cancer risk in offspring compared to exposure to a high fat diet alone. The increase in risk persisted for three generations. Likewise, Dr. Sandra Haslam (Michigan State University) presented results from a mouse study that showed a diet high in animal fat during puberty led to the development of tumors similar to human triple negative breast cancer. Dr. Haslam pointed out a human study published in 2014 (Farvid, MS et al BMJ:2014; 348 : g3437) that parallels these animal results. In the Farvis study, in 2830 cases of breast cancer over a 20 year period, they found that a higher intake of total red meat was associated with increased risk overall. They concluded that higher intake of animal fat during early adulthood may be considered a risk factor for breast cancer.
Dr. Melissa Troester (University of North Carolina-Chapel Hill) discussed research looking at specific features of breast tissue in association with exposures such as obesity, pregnancy and exposures to other estrogens. It is well established that “dense” breast tissue is a risk factor for breast cancer in and of itself – not just because it make tumors harder to find on a mammogram. And we have also long known that giving birth conveys a “protective” effect against breast cancer, and that women who have no children or have them later in life are at a higher risk for breast cancer. Dr. Troester, though, identified the period after giving birth as a window of greater risk due to pregnancy being a period of high epithelial density. This epithelial density gradually decreases for a number of years after giving birth before the protective effect of parity begins. Epithelial density seems to track with mammographic density – in other words, it is concentrated in areas of high mammographic density.
Dr. Michael Gould (the UW – Madison researcher with whom we work) has, in his past work, identified three genetic loci that appear to act during the young adult window of susceptibility. All three loci control gene expression that could result in susceptibility or resistance to breast cancer. Dr. Gould’s lab is initiating research to identify how those loci respond to certain environmental exposures during this window and will be attempting in one study to mimic resistance effects using an external compound. Wisconsin BCERP partners suggested several environmental “toxins” that should be investigated and we will be working with Dr. Gould on another arm of this research in which his hypotheses will be tested in a human study.
Opening the summit in her keynote address, Sarah Gehlert, PhD emphasized the complexity of breast cancer – the determinants of which occur at “many levels of influence, from the cellular to the societal, which interact with one another in complex ways across the life cycle.” For instance, chemical and social environmental exposures are connected because social impacts (like low socio-economic status) are tied to exposure to chemicals. Likewise, there are social determinants of obesity (a breast cancer risk factor), such as health literacy and features of a person’s built environment (safe places for physical activity, multiple fast food outlets and few options for fresh vegetables/fruits). She identified six levels of influence to breast cancer risk and outcomes (Warneck, Oh, Gehlert et al AJPH 2008):
- Social conditions and policies
- Social relationships
- Individual risk
- Biologic/Genetic pathways
All of the above are pathways impacting breast cancer risk and outcome, which, from my perspective, means there is a role for nearly everyone to play in reducing breast cancer risk. You don’t need to be a researcher if you can have an impact on the social conditions and policies that increase risk. You can manage your own personal risk with some knowledge, but you can also share risk reduction strategies with others. Very little can be accomplished working in silos. As more information becomes available from BCERP research, it will be important that collaborations be forged to address risk factors, “from the cellular to the societal.”
The Wisconsin BCERP Community Partners are excited to be participating in what we consider to be a much needed approach to breast cancer control – to look upstream as far as we can with the specific purpose of identifying targets that can be influenced in ways that reduce risk. Watch for more exciting news from your WI-BCERP Partners in the coming year as a new round of NCI/NIEHS funding gets underway.