title: Screening for Chemical Contributions to Breast Cancer Risk: A Case Study for Chemical Safety Evaluation.
abstract: BACKGROUND
  Current approaches to chemical screening, prioritization, and assessment are being reenvisioned, 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  The HIA-BC identifies assays capable of detecting alterations to biological processes relevant to breast cancer, including cellular and 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.
  
  
  CONCLUSIONS
  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 end points not currently evaluated by federal testing programs, including altered mammary gland development, Her2 activation, progesterone receptor activity, prolactin effects, and aspects of estrogen receptor β activity. This approach could be extended to identify the biological processes and screening methods relevant for other common diseases.
authors.affiliation: Center for Occupational and Environmental Health, School of Public Health, University of California, Berkeley, Berkeley, California, USA.
authors.forename: Megan R
authors.initials: MR
authors.lastname: Schwarzman
authors.forename: Janet M
authors.initials: JM
authors.lastname: Ackerman
authors.forename: Shanaz H
authors.initials: SH
authors.lastname: Dairkee
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Fenton
authors.forename: Dale
authors.initials: D
authors.lastname: Johnson
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Navarro
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Osborne
authors.forename: Ruthann A
authors.initials: RA
authors.lastname: Rudel
authors.forename: Gina M
authors.initials: GM
authors.lastname: Solomon
authors.forename: Lauren
authors.initials: L
authors.lastname: Zeise
authors.forename: Sarah
authors.initials: S
authors.lastname: Janssen
mesh_terms: D001681:Biological Assay; D001943:Breast Neoplasms / Q000139:chemically induced*; D002273:Carcinogens / Q000633:toxicity*; D004249:DNA Damage; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D006801:Humans; D009153:Mutagens / Q000633:toxicity*; D010865:Pilot Projects; D012306:Risk; D018675:Toxicity Tests
chemical_list: D002273:Carcinogens; D004967:Estrogens; D009153:Mutagens