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.

Citation: Schwarzman MR, Ackerman JM, Dairkee SH, Fenton SE, Johnson D, Navarro KM, Osborne G, Rudel RA, Solomon GM, Zeise L, Janssen S. 2015. Screening for chemical contributions to breast cancer risk: a case study for chemical safety evaluation. Environ Health Perspect 123:1255–1264;  http://dx.doi.org/10.1289/ehp.1408337

Address correspondence to M.R. Schwarzman, 50 University Hall, #7360, Berkeley, CA 94720-7360 USA. Telephone: (510) 643-4685. E-mail: [email protected]

We acknowledge the other members of the Breast Cancer and Chemicals Policy (BCCP) project expert panel: S. Braun, V.J. Cogliano, W. Goodson, J. Guth, J. Latimer, R. Melnick, R. Morello-Frosch, and C. Sonnenschein, whose input informed the project’s findings. T. Steuve made additional contributions to the research.

This work was funded by the California Breast Cancer Research Program, University of California Office of the President (grant #15QB-8001), with partial support for J.M.A. and R.A.R. from a grant from Avon Foundation for Women.

The information in this document has been subjected to review by the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH) and approved for publication. This article is the work product of an employee of the NIEHS/NIH; however, the statements, opinions or conclusions contained therein do not necessarily represent the statements, opinions or conclusions of the NIEHS, NIH, or the U.S. Government. Likewise it does not necessarily represent the opinion of the California Environmental Protection Agency or its Office of Environmental Health Hazard Assessment.

J.M.A. and R.A.R. are employed at Silent Spring Institute, a nonprofit scientific research organization dedicated to studying environmental factors in women’s health. The Institute is a 501(c)3 public charity funded by federal grants and contracts, foundation grants, and private donations, including those from breast cancer organizations. The authors declare they have no actual or potential competing financial interests.

Received: 26 February 2014 Accepted: 20 May 2015 Advance Publication: 2 June 2015 Final Publication: 1 December 2015

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