Annual Extended Exposures Conference:
Breast Cancer and the Environment Research Program – November 15-16, San Francisco CA
— Dawn Anderson, WBCC Executive Director
The Breast Cancer and the Environment Research Program (BCERP) is conducting studies at eight centers around the country investigating the effects of environmental exposures on breast cancer risk. Each research site is teamed with Community Partners, who help to “translate” the research into lay language and share that information with the public. Key findings will then be shared as public health messages meant to positively influence behaviors that would reduce risk. The WBCC, along with representatives from Susan G Komen– South Central WI, The Wisconsin Cancer Council, and UW-Milwaukee School of Nursing, is a Community Partner for BCERP research being conducted at University of Wisconsin Madison by Michael Gould, PhD and Amy Trentham-Dietz, PhD . I was pleased to be able to attend this important and informative conference.
This year’s Annual Conference focused on four distinct Windows of Susceptibility (WOS) – periods in a woman’s lifespan that represent particular vulnerability to environmental impacts, or stressors. Dr. Linda Birnbaum (see below) aptly refers to this as “throwing a monkey wrench in the works” at times when cellular activity is very high. Researchers presented results from studies on the In Utero, Puberty, Pregnancy and Menopause windows. The following article presents some of the highlights from the conference.
The opening Keynote Address was given by Dr. Linda Birnbaum, Director of The National Institute of Environmental Health Sciences (NIEHS). NIEHS has recently adopted a new strategic plan which, as she pointed out, emphasizes some of the key goals of the BCERP program – research into susceptibility, training and outreach/education. Some of the key points from her address:
- We’re beginning to see a reverse in the breast cancer incidence decline witnessed after the wholesale drop off of hormone replacement therapy (HRT) use in the early 2000’s. (As a result of increased breast cancer risk shown in the estrogen + progestin arm of the Women’s Health Initiative Study, that arm of the study was stopped in 2002 and women nationwide stopped taking the combination HRT.)
- Established risk factors for breast cancer account for between 25-50% of U.S. cases, meaning that environmental factors could explain up to 75% of them.
- The DOHAD Paradigm (Developmental Origins of Health and Disease) holds that environmental insults during early development may increase disease risk later in life. This is the basis for “Windows of Susceptibility” studies.
- The biggest policy changes will produce the biggest cost savings. Individual interventions produce the least cost savings.
The In Utero WOS
The general take home message in these sessions was that chemical exposures in utero (in animal studies) resulted in marked differences in the timing of mammary gland development, in the density of mammary tissue, and in the development of tumors. Two studies separately showed delayed breast development as a result of in utero exposure to Dioxin, PFOA’s (a chemical used in Teflon, Scotchguard, Gortex, etc), and BPA. While the exact implications are not clear yet, it is clear that exposures to certain chemicals do disrupt the normal development of the breast and, therefore, can affect the timing and progress of Puberty.
The Puberty WOS
The onset of puberty is a critical piece in the breast cancer risk puzzle. Contrary to general understanding of the term, for scientific purposes there are several markers of puberty that researchers look at. Breast development (the first palpable tissue), menarche (first period), and growth spurt in height are distinct markers. During this period of development, with increased cell proliferation and activity, the breast is more vulnerable to DNA damage and other insults that destabilize the “integrity” of the cells. Early menarche is considered a risk factor because it represents an extended period of time in a woman’s life that she is exposed to circulating estrogen (likewise, late menopause is a risk factor).
Dr. Elisa Bandera (Cancer Institute of New Jersey) presented findings from an analysis of 163 girls, aged 9 and 10, in which urinalysis measured mycoestrogens and compared those findings with body size and development. Mycoestrogens have received little attention in research but Dr. Bandera characterized it as the most important contaminant in the food chain. It is a secondary metabolite of a fungus which is not visible, thrives in heat/high humidity and is heat stable – it is not destroyed by canning or other processes. It is found in grains, plant products and animal products. Zeranol, a synthetic of the natural mycoestrogen zearalenone, is widely used as a growth promoter in animal husbandry in the United States. It has been banned for that use in the European Union and other countries. Mycoestrogens were found in the urine of approximately 79% of the girls, and these levels were predominately associated with beef and popcorn intake. These girls also tended to be shorter and less likely to have reached the onset of breast development. Since this may have been the first evaluation of urinary mycoestrogens and their potential effects on girls, Dr. Bandera notes that their findings need replication in larger studies.
Another area that has not been studied is whether the effect of early life exposures on breast cancer are greater in individuals with a family history of breast cancer than in those with average risk. Dr. Esther John (Cancer Prevention Institute of California) introduced the LEGACY Girls Study. The study was initiated in 2011 at five centers in the U.S. and Canada with a goal of recruiting 950 girls ages 6-13, and their mother or guardian, for a five year study. The girls are being followed with repeated biospecimen collection at six month intervals to study childhood exposures in relation to pubertal development. It will then look at these early exposures in relation to intermediate markers of breast cancer risk and whether those markers operate differently in girls with family history.
The Pregnancy WOS
While in the long run, full term pregnancy and childbearing appear to confer a protective effect for women developing breast cancer at menopause, there is an emerging area of research around Pregnancy Associated Breast Cancer (PABC). This is a unique part of young women’s breast cancer that Dr. Virginia Borges (University of Colorado Cancer Center) proposes includes two biologically distinct conditions: those diagnosed during pregnancy and those diagnosed post partum. Post partum breast cancers occur in significantly larger numbers and have higher mortality. The window for this period of heightened risk lasts from 6-8 years post pregnancy. PABC is attributed to greater than 40% of young women diagnosed. The method by which this is explained is related to involution – a normal physiologic event related to weaning or the post partum breast returning to its pre-pregnancy state. This period of involution is a highly pro-inflammatory state in which the threat of tumor growth and proliferation and metastasis is enhanced. An increase in COX-2 (an enzyme responsible for inflammation) was observed in animal model studies. Dr. Borges suggests that with further research that could be translated into safe human studies, it is possible that treatment with non steroidal anti-inflammatory drugs could be introduced during the post partum period to reduce risk in high-risk post partum women.
The Menopause WOS
Our own Dr. Amy Trentham-Dietz (UW Madison) presented findings from a small but interesting study into the effects of BPA on breast density – another known risk factor. BPA is a ubiquitous compound found in plastics, the linings of food product cans, and even the ink on register receipts. It is also a known endocrine disruptor. Dr. Trentham-Dietz looked at 264 postmenopausal women for an association between circulating serum levels of three phenols, including BPA, with mammographic breast density. The data suggest that the women with the highest levels of BPA also had the highest levels of breast density. Obese women were less likely to have elevated density. In thin women, density was elevated with BPA. This preliminary evidence should inform further study on the effects of xenoestrogens like BPA on the risk of breast cancer.
The Madison research team and Community Partners are proud to be hosting the 2013 Annual Conference in Madison November 7 and 8, 2013. Please save the date now. The Wisconsin Community Partners are developing an email list for those interested in learning more as the studies progress, being notified of registration for the conference, and to be made aware of opportunities to attend other presentations. To sign up, please send an email to WBCC with the subject line “BCERP”.
For more information on BCERP: www.bcerp.org