Prenatal Environmental Exposures: Lifelong Impact on Mammary Gland Development and Function
Suzanne E. Fenton, PhD, National Toxicology Program, NIEHS/NIH
Breast cancer is the second leading cause of cancer mortality in U.S. women and it is becoming increasingly apparent that the environment plays a significant role in the etiology of the disease. The role that environmental chemicals may have in initiation or promotion of this disease is unclear, and very few chemicals on the U.S. market have been evaluated for their effects on the breast. Therefore, there is a need for future test guidelines that specifically evaluate mammary/breast tissue in health screening assessments for all chemicals/pharmaceuticals. We have performed numerous studies in rodent models to determine the effects of prenatal/neonatal exposure to environmental factors on mammary gland development, function and tumor susceptibility. Important effects included persistent or preneoplastic developmental changes, altered lactation, and/or altered tumor risk over the life course. Additionally, NTP and IARC carcinogenesis reports, academic and government rodent model research, and/or epidemiological studies have reported effects of environment on breast development, lactation, and cancer risk. Early life exposure was critical for the effects in many studies, including those in humans; i.e., ionizing radiation, dioxin, diethylstilbestrol, and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT). Although mammary end points are not often included in chemical testing, in several rodent studies, mammary effects are reported to be the most sensitive to the environmental factor tested (ex., genistein and bisphenol A). Endocrine disruptors may influence tumor susceptibility (i.e., by changing the microenvironment) without actually causing tumor development. So with all of this evidence, why is it that mammary data is seldom used in risk assessment of chemicals or to make decisions on any type of regulation? One reason may be that persistently altered mammary gland development is not considered to be an ‘adverse’ outcome by most risk assessors. Additionally, resources are seldom available to confirm the mammary-specific effects in more than one species, to determine the mechanism of effect, or to determine the lowest effective dose; characteristics that greatly aid in risk assessment. It is imperative that the environmental influences of breast cancer be identified if this deadly disease is to be prevented, which would require evaluation of mammary tissue in all chemical testing.
Disclaimer: This abstract does not necessarily reflect NIEHS policy.