Evaluating chemical effects on mammary gland development: A critical need in disease prevention

Abstract

Although understanding the environmental factors that contribute to breast cancer could improve disease prevention, standard chemical testing protocols do not adequately evaluate chemicals' effects on breast development. Evidence suggests: (1) mammary gland (MG) development is a complex process that extends from gestation through fetal and neonatal growth, puberty, and pregnancy; (2) altered MG development can increase the risk of breast cancer and other adverse outcomes; and (3) chemical exposures during susceptible windows of development may alter the MG in ways that increase risk for later disease. Together, these highlight the need to better understand the complex relationship between exposure to endocrine disrupting compounds (EDCs) and the alterations in MG morphology and gene expression that ultimately increase disease risk. Changing guideline toxicity testing studies to incorporate perinatal exposures and MG whole mounts would generate critical knowledge about the effects of EDCs on the MG and could ultimately inform disease prevention.

Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development

“…Developing tissues, including that of the mammary gland, can be particularly sensitive to environmental chemical insults (Rudel, et al 2011). Several common environmental chemicals have been shown to adversely impact mammary glands at doses below those typically used in toxicological studies (Osborne, et al 2015). A unique aspect of our study is the use of low doses that are biologically relevant to human exposure.…”

The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure

“…Because of the potential for increased lifetime susceptibility to disease or dysfunction, pubertal assessments of chemical effect performed in rodent models should include an evaluation of the mammary gland. This suggestion has recently been echoed by the scientific community [53, 54, 55]. It will also be necessary to evaluate for changes in breast development based on early life or cord blood PFOA levels in future epidemiological studies.…”

A comprehensive review of regulatory test methods for endocrine adverse health effects

“…As an enhancement to the cancer bioassay for the detection of mammary tumors, the whole mount procedure was discussed among OECD experts but it was decided to be too difficult to implement based on the high degree of uncertainty with respect to the interpretation. A protocol for evaluating whole mounts of mammary glands was judged to need additional development and interlaboratory validation to demonstrate consistency among different laboratories (Osborne et al 2014). Regulatory experts concurred that the whole mount procedure was not ready for incorporation into the OECD 452 and 453 TGs at that time.…”