Windows of Susceptibility

/Windows of Susceptibility
Windows of Susceptibility2019-03-06T18:36:41+00:00

In Connecting Science & Society:

The Breast Cancer and Environment Research Program (BCERP) includes researchers, community partners (CP), and community outreach translation core members (COTC) who are pursuing novel epidemiological, clinical, and population studies. Utilizing human and animal models, focusing on gene environment interactions and environmental influences contributing to breast cancer risk. Looking over the entire life span of an organism, the investigators will focus on various end points, or “Windows of Susceptibility.”Investigators have partnered with breast cancer advocate(s) and members of the engaged community to facilitate the study design as well as translate and communicate findings back to the community, policy makers and other stakeholders.

Mount Sinai School of Medicine
Breast Cancer Genomics in Windows of Susceptibility to Endocrine Disruptors
PI: S Teitelbaum, Ph.D. and Jia Chen, ScD
CP: Huntington Breast Cancer Action Coalition, Inc.
Great Neck Breast Cancer Coalition

Michigan State University
Pubertal High Fat Diet: Effects on Inflammation, Mammary Development & Cancer
Co-PIs: S. Haslam, Ph.D., Richard Schwartz, Ph.D.
CP: Michigan Breast Cancer Coalition

Public Health Institute & Columbia University
Pedigree: Prenatal Environmental Determinants of InterGenerational Risk
Co-PIs: B Cohn, Ph.D. and M Terry, Ph.D.
CP Rep: Women’s Foundation of California

University of Alabama at Birmingham
Combinational Environmental Chemicals Altering Susceptibility for Mammary Cancer
PI: C Lamartiniere, Ph.D., T Huang, Ph.D., J Russo Ph.D.
CP: Susan G Komen for the Cure, North Central Alabama Affiliate

University of California San Francisco
Environmental Effect on the Mammary Gland across the Lifespan
PI: Z Werb, Ph.D.
CP: Zero Breast Cancer

University of Cincinnati
Susceptible Window of High Fat/Bisphenol A Programming of Breast Cancer Risk
PI: S. Ho, Ph.D.
CP: Pink Ribbon Girls

University of North Carolina Chapel Hill
Pregnancy, Obesogenic Environments and Basal-like Breast Cancer
Co-PIs: M. Troester, Ph.D., Lisa Makowski, Ph.D.
CP: UNC Chapel Hill Gillings School of Global Public Health

University of Wisconsin Madison
Genetics of Breast Cancer Risk at Windows of Exposure
PI: M. Gould, Ph.D.
CP Rep: Susan G Komen, Madison Wisconsin Affiliate

Adulthood after childbirth (parous) and adulthood before childbirth (nulliparous)

Adapted from Barton 2005 and Pryor 2000

Barton HA. Computational pharmacokinetics during developmental windows of susceptibility.
J Toxicol Environ Health A 2005 Jun 11;68(11-12):889-900.

Pryor JL, Hughes C, Foster W, Hales BF, Robaire B. Critical windows of exposure for children’s health:
the reproductive system in animals and humans. Environ Health Perspect 2000 Jun;108 Suppl 3:491-503

Many  drugs, treatments and cures for human diseases have been developed with the use of animal models. The use of animal models allows researchers to investigate disease in ways which would be inaccessible in a human patient. Animal models that imply a level of harm would not be considered ethical to inflict on a human being.

Rat models can determine what chemicals are potentially harmful, and with this information allows the community to make a decision. There remains a debate among investigators and policy makers on when to take “action”.

The outcome of animal model studies, contribute to our understanding of gene environment interaction and in many cases parallels human data. Some scientists still believe that no regulatory action should be taken without significant human data. Most of the advocate community supports the precautionary approach and encourages taking preliminary action if a chemical or chemicals in a product show a risk of harm.

  • In order to simulate a real world experience when using personal care products, exposure regimens in animal models will include an individual chemical as well as a combination of chemical doses at biologically relevant levels.
  • The animals will be exposed to the chemicals at different developmental end points, Windows of Susceptibility (WOS): prenatal, neonatal, pre-pubertal, pubertal, parous, and nulliparous.
  • In both women diagnosed with breast cancer and the animals in the experimental models, any changes in mammary tissue will be assessed to determine if cell abnormalities occurred.

These studies will enable us to identify modifiable breast cancer risk factors and make public health recommendations that can be easily implemented.

Of Mice of Women

Of Mice and Women: Modeling Breast Cancer and the Environment from Zero Breast Cancer on Vimeo.

The “Of Mice and Women” video was developed by the Bay Area Breast Cancer and the Environment Research Center (BABCERC) Community Outreach and Translation Core with Mary Helen Barcellos-Hoff, Ph.D., Associate Professor in the Department of Radiation Oncology at New York University Langone School of Medicine. In the video Mary Helen Dr. Barcellos-Hoff, Ph.D. discusses why different types of rat models are used to study aspects of breast cancer biology.The goal of the video and scientific glossary is to serve as an educational tool for breast cancer advocates and community members to facilitate a greater understanding of why rat models are used in breast cancer prevention research.

Endocrine Disrupters

Our Endocrine system regulates hormones that influence every cell, tissue, organ and function in our bodies. The endocrine system regulates mood, growth and development, tissue function, metabolism, as well as sexual function and reproductive processes.

  • An endocrine disruptor is a chemical that alters normal function of this system. A variety of chemicals have been found to disrupt the endocrine system; some mimic hormones, while others can block these hormones from doing their job.
  • In their everyday lives, women are exposed to combinations of potential endocrine disrupting chemicals through personal care products, certain plastics and pesticides, pharmaceuticals, cleaning products, foods and beverages. These exposures occur throughout a woman’s lifetime.
  • Although there are a multitude of potentially endocrine disrupting chemicals that can be studied, Mount Sinai School of Medicine has chosen to focus on three common exposures: diethyl phthalate , methylparaben , and triclosan . All have some evidence of hormonal activity that is suspected to produce adverse health effects.

Triclosan– Commonly used antimicrobial found in personal care and household products ranging from toothpaste, deodorant and hand soap to cutting boards and inner soles of shoes.

  • The hormonal activity of triclosan has not been clearly established and results of many investigations are conflicting.
  • Dermal and oral exposure are the main exposure routes and triclosan has been measured in breast milk indicating that this chemical may act directly on breast tissue. http://www.ewg.org/node/26701
  • There is limited research on triclosan exposure and breast cancer risk.

Methylparaben– Commonly used as antimicrobial preservatives in personal care products, cosmetics, pharmaceuticals and in the processing of foods and beverages.

  • Parabens have been hypothesized to play a role in breast cancer due to their potential estrogen activity.
  • There is limited research on paraben exposure and breast cancer risk.

Diethyl Phthalate– Exposures are high because they are so widely used.

  • Diethyl phthalate (DEP) is found more often in personal care products (fragrances, shampoo, cosmetics and nail polish).
  • Not required to be on product labels, including medications.
  • Phthalates mimic estrogen, not only do these affect females but they also have anti-androgenic effects on males. In both male and females these chemical exposures may have adverse reproductive outcomes.

Studies and publications on the adverse health effects of triclosan, methylparaben and diethyl phthalate can be found below.

Our daily exposures add up. How many times a day do you use cosmetics, personal care products, pharmaceuticals, and/or perfumes? Does this combination have toxic effects on health?

With ubiquitous exposure to Endocrine Disrupters (EDs) and rising concerns about the health consequences of these chemicals, studying the role of EDs in breast carcinogenesis is urgently needed. In addition, it is highly important from the public health point of view to develop intervention strategies to mitigate the adverse effects of EDs. Should the epidemiologic findings and results from animal studies support the role of EDs in breast cancer etiology, public health recommendations should be implemented. Choices and changes in your everyday behaviors also can be easily applied.

It is important as a community to increase our awareness.

Studies and publications on Adverse Health Effects of Triclosan, Methylparaben, Diethyl Phthalate (Phthalates)