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Breast Cancer and the Environment and NIEHS Research Programs Leslie Reinlib, PhD Program Director National Institute of Environmental Health Sciences. Breast Cancer: Some History. Queen Atossa Persia 500 BCE. Hendrickje Stoffels Holland 17 th Century.
Breast Cancer and the Environment and NIEHS Research ProgramsLeslie Reinlib, PhDProgram DirectorNational Institute of EnvironmentalHealth Sciences
Queen Atossa Persia 500 BCE
Hendrickje Stoffels Holland 17th Century
Bathsheba’s Breast by James Olson 2002
William Stewart Halstead 1852 - 1922
Bernard Fisher 1920 -
B. Fisher, S. Anderson, J. Bryant, et al., N Engl J Med, 2002, vol. 347, pp. 1233-1241
US 5-Year Survival Rates
1975 Overall 75%
2006 Overall 89%
SEER Cancer Statistics Review
National Cancer Institute
Rockhill et al Am J Epi 147: 826-833 (1998)
Sakorafas Cancer Treat Rev 29: 79-89 (2003)
American Cancer Society Fact Sheet 2002
ChemicalUS ExposureBC ConnectionPhysiologyOther
DES pregnant women risk & mortality birth wt; early
(estrogen 1940-1971; in DES mothers (30-40%) thelarche;
disrupt.) cattle feed=>1979 & daughters (20%-2.5X) estrogen mimic;
hormone recptr; etc
Phytoestrogens beans, soy, estrogen in chng estrogen
flax, grains Chinese women production & brkdn
Omega3 fish may BC risk(?) Fats/FA may little info
Fatty Acids estrogen; on diet
early puberty after BC
DDT/DDE ended 1970 no direct evidence lactation? low levels breast milk
HRT hot flashes recurrence 3x estrogen
Source: Cornell Univ Program on Breast Cancer and Environmental Risk Factors in NY State
Life Cycle of Breast Development
Russo J & Russo IHJournal of Mammary Gland Biology and Neoplasia;3:49-61 (1998)
Russo etal, Mammary Gland Architecture and Susceptibility of Human Breast to Cancer. Breast Journal; 7:278-291 (2001)
Basic Science Researchers
Community Advocates and Members
Two parallel projects
Environmental Effects on the Molecular Architecture and Function of the Mammary Gland Across the Lifespan
Aims: Explore normal development & chemically - induced changes in the architecture of the mammary gland
Environmental and Genetic Determinants of Puberty
Aims: Determine key environmental risk factors, genetic susceptibility on breast development (thelarche) & menarche. Study will focus on approx 1500 girls of diverse racial groups from across the nation.
Robert Bornschein, Ph.D.
University of Cincinnati
Puberty & Cancer Initiation: Environment, Diet, & Obesity
Jose Russo, M.D.
Fox Chase Cancer Center
Centers for Environment and Mammary gland Development
Sandra Z. Haslam, Ph.D.
Michigan State University
Breast Cancer and the Environment Research Center
Robert A. Hiatt, M.D., Ph.D.
University of California at San Francisco
Bay Area Breast Cancer & the Environment Research Center
Biomarker discovery for tumor initiation
Diet, age, environmental chemicals, and irradiation examined at critical Windows of Susceptibility
Role in altering mammary gland architecture of estrogen-active chemicals during critical periods of development
Importance during gestation and lactation of high fat diets, elevated progesterone, estrogen, carcinogens
Implications for breast cancer risk of modifiable factors that influence female sexual maturation
Dietary factors: PAH, alkyl amines (PhiP*), omega & gamma fatty acids, PUFA, phytoestrogens
Carcinogens: benzo(a)pyrene*, DMBA*, lead, PCB, PBDE, ochratoxin
Endocrine Disruptors: dioxin, ICZ*, phthalates
Other: irradiation*, energy balance, activity
* animal studies
Community Input into Exposures to Track in Human/Laboratory Studies
Mary Wolff, Susan Teitelbaum, Gayle Windham, Susan Pinney, Julie Britton, Carol Chelimo, James Godbold, Frank Biro, Lawrence H. Kushi, Christine M. Pfeiffer, Antonia M. Calafat. Pilot Study of Urinary Biomarkers of Phytoestrogens, Phthalates, and Phenols in Girls. Env Health Persp 2007; 115: 116.
Windham GC, Pinney SM, Sjodin A, Lum R, Jones RS, Needham LL, Biro FM, Hiatt RA and Kushi LH. (2010) Body burdens of brominated flame retardants and other persistent organo- halogenated compounds and their descriptors in US girls. Environ. Res 2010
Zhao, Y, Tan YS, Haslam S, Yang C. PFOA effects on steroid hormone and growth factor levels mediate stimulation of peripubertal mammary gland development in C57Bl/6 mice. Toxicology Sciences 2010.
Mukhopadhyay R, Costes SV, Bazarov AV, Hines WC, Barcellos-Hoff MH, and Yaswen P. Promotion of Variant Human Mammary Epithelial Cell Outgrowth by Ionizing Radiation: an Agent-Based Model Supported by In Vitro Studies. Breast Cancer Res. 2010; 10: R11.
MS Wolff, et al. Relationships between Urinary Biomarkers of Phytoestrogens, Phthalates, and Phenols and Pubertal Stages in Girls. Env Health Persp 2010
Early Environmental Exposures
Les Reinlib, PhD – BCERP Director & Program Administrator
Elizabeth Maull, PhD – Program Administrator
Caroline Dilworth, PhD – Program Administrator
Gwen Collman, PhD – Director, Extramural Research and Training