California Breast Cancer Research Program
Screening for Chemical Contributions to Breast Cancer Risk: A Case Study for Chemical Safety Evaluation.
- Author(s): Schwarzman, Megan R
- Ackerman, Janet M
- Dairkee, Shanaz H
- Fenton, Suzanne E
- Johnson, Dale
- Navarro, Kathleen M
- Osborne, Gwendolyn
- Rudel, Ruthann A
- Solomon, Gina M
- Zeise, Lauren
- Janssen, Sarah
- et al.
Published Web Locationhttp://ehp.niehs.nih.gov/1408337/
Current approaches to chemical screening, prioritization and assessment are being re-envisioned, driven by innovations in chemical safety testing, new chemical regulations, and demand for information on human and environmental impacts of chemicals. To conceptualize these changes through the lens of a prevalent disease, the Breast Cancer and Chemicals Policy project convened an interdisciplinary expert panel to investigate methods for identifying chemicals that may increase breast cancer risk.
Based on a review of current evidence, the panel identified key biological processes whose perturbation may alter breast cancer risk. We identified corresponding assays to develop the Hazard Identification Approach for Breast Carcinogens (HIA-BC), a method for detecting chemicals that may raise breast cancer risk. Finally, we conducted a literature-based pilot test of the HIA-BC.
The HIA-BC identifies assays capable of detecting alterations to biological processes relevant to breast cancer, including cell molecular events, tissue changes, and factors that alter susceptibility. In the pilot test of the HIA-BC, chemicals associated with breast cancer all demonstrated genotoxic or endocrine activity, but not necessarily both. Significant data gaps persist.
This approach could inform the development of toxicity testing that targets mechanisms relevant to breast cancer, providing a basis for identifying safer chemicals. The study identified important endpoints not currently evaluated by federal testing programs, including altered mammary gland development, Her2 activation, progesterone receptor activity, prolactin effects, and aspects of ER-beta activity. This approach could be extended to identify the biological processes and screening methods relevant for other common diseases.