Environment and Breast Cancer: Science Reviews

We all carry a body burden from the chemical swirl of our environment. But when does that burden grow too heavy? Which chemicals can be tolerated, and which trigger or hasten the development of cancerous cells?

To help clarify the chemical risks for breast cancer, Silent Spring Institute has compiled the most comprehensive review to date of scientific research on environmental factors that may increase risk of the disease. The study findings—entitled “Environmental Factors in Breast Cancer”—appeared in the June 15, 2007 issue of the American Cancer Society’s journal Cancer.

The state-of-the-science review—commissioned by Susan G. Komen for the Cure and conducted by Silent Spring Institute in collaboration with researchers from Harvard University, Roswell Park Cancer Institute, and the University of Southern California—involved the collection and assessment of scientific studies on potential links between specific environmental factors and breast cancer.

The research team examined modifiable influences on breast cancer. The result of this portion of the work—the Epidemiology Reviews Database—includes critical reviews of approximately 450 primary epidemiologic research articles on breast cancer and diet, environmental pollutants, physical activity, and body size. This database, which includes articles published through June 2006, is updated periodically.

After synthesizing data from national and international sources, the researchers also identified 216 chemicals that cause mammary tumors in animals. They then used that information to create a searchable online database featuring detailed information on the carcinogens. The Mammary Carcinogens Review Database offers summary assessments of the carcinogenic potential of each chemical, data on mutagenicity, opportunities for exposure in the general population and for women at work, and other characteristics of chemical use, sources, and regulation. The database includes references to 900 studies.

“While it’s disturbing to learn that so many chemicals may be linked to breast cancer,” says Dr. Julia Brody, executive director of Silent Spring Institute, “we must remember that we have a great opportunity to save thousands of lives by identifying those links, limiting exposure, and finding safer alternatives. It’s critical that we integrate this information into policies that govern chemical exposures.”

Review Articles

Reviews and commentaries on the Environment and Breast Cancer Science Reviews databases were published in Environmental Factors in Breast Cancer, a supplement issue of Cancer.

Evidence from Humans


Environmental Pollutants and Breast Cancer: Epidemiologic Studies

Brody, JG, KP Moysich, O Humblet, KR Attfield, GB Beehler, RA Rudel. 2007. Cancer, 109 (S12): 2667–2712. [online May 14, 2007, print June 15, 2007]
Article (pdf), Summary (pdf)

Diet and Breast Cancer: A Review of the Prospective Observational Studies

Michels, KB, AP Mohllajee, ER Bahmanyar, GB Beehler, KP Moysich, 2007. Cancer, 109 (S12): 2712–2749. [online May 14, 2007, print June 15, 2007]
Article (pdf), Summary (pdf)
Evidence from Animals


Chemicals Causing Mammary Gland Tumors in Animals Signal New Directions for Epidemiology, Chemicals Testing, and Risk Assessment for Breast Cancer Research

Rudel, RA, KR Attfield, J Schifano, JG Brody. 2007. Cancer, 109 (S12): 2635–2667. [online May 14, 2007, print June 15, 2007]
Article (pdf), Summary (pdf)
Commentaries on the Science Reviews


Environment Pollutants, Diet, Physical Activity, Body Size, and Breast Cancer: Where Do We Stand in Research to Identify Opportunities for Prevention?

Brody, JG, RA Rudel, KB Michels, KP Moysich, L Bernstein, KR Attfield, S Gray. 2007. Cancer, 109 (S12): 2627–2634. [online May 14, 2007, print June 15, 2007]
Commentary (pdf), Summary (pdf)

Advocate Perspective: Advancing Science-Based Approaches to Breast Cancer Prevention

Susan G. Komen for the Cure. 2007. Cancer, 109 (S12): 2750–2751. [online May 14, 2007, print June 15, 2007]
Commentary (pdf)
 

Epidemiology Reviews Database

In a systematic search of scientific research indexed in the online medical resource PubMed, the research team identified 450 primary epidemiologic research articles on breast cancer and environmental pollutants, physical activity, body size, and prospective studies of dietary factors.

For each article, the Science Review database includes quick access to basic study information and critical assessments:

  • the bibliographic citation and abstract or a link to a copyrighted abstract;
  • information about the study population, exposure assessment method, study design, results, and analyses of ethnic minority populations, early life exposures, or interactions with inherited genes;
  • assessments of the study’s strengths and weaknesses; and
  • interpretation of the study’s results.

Articles are searchable by topic. In addition, the database includes about 50 citations to review articles, methods papers, and exposure assessments that aid in interpreting the primary research. The database includes studies of environmental pollutants published through June 2006 and in other topic areas through May 2005. Review methods are described in the review articles published in Cancer.

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Body Size

The evidence is now substantial that body size—including postmenopausal weight gain and a high waist-to-hip ratio—is associated with a higher breast cancer risk. Public health initiatives and research to identify the most effective strategies for preventing obesity later in life should be breast cancer priorities.
See Science Review • body size

Diet

Studies that monitored diet before diagnosis do not provide consistent evidence of associations with breast cancer. The research team considered studies of fat intake; fruits and vegetables; antioxidant vitamins (A, C, E, and beta-carotene); serum antioxidants; carbohydrate intake; glycemic index and glycemic load; dairy consumption, including vitamin D; soy products and isoflavones; green tea; heterocyclic amines; and adolescent diet. But after reviewing the prospective epidemiologic studies conducted on diet and breast cancer incidence and gene-diet interactions and breast cancer incidence, the research team found no association that was consistent, strong, and statistically significant, with the exception of alcohol intake, overweight, and weight gain. The researchers noted that this apparent lack of association between diet and breast cancer may reflect a true absence of an association or weaknesses in the research methods, such as errors in measuring aspects of diet, lack of sufficient follow-up, and focus on diet in adulthood rather than early life. The research team emphasized that women can reduce their breast cancer risk by avoiding weight gain after menopause and restricting their consumption of alcohol.
See Science Review • diet
Review Article

Early Life Exposures

See Science Review • early life exposures

Environmental Pollutants

Laboratory research has shown that many environmental pollutants cause mammary gland tumors in animals; are hormonally active, specifically mimicking estrogen, which is a breast cancer risk factor; or affect susceptibility of the mammary gland to carcinogenesis. The review of epidemiology related to environmental pollutants shows that research in this area is still relatively sparse. Results in recent years, however, have begun to show evidence of increased risk associated with exposure to polychlorinated byphenols (PCBs)—banned chemicals previously used in electrical equipment and other products—in genetically susceptible women and to polycyclic aromatic hydrocarbons (PAHs), which are ubiquitous air pollutants from vehicle exhaust and other sources of combustion byproducts. Results of studies of organic solvents and dioxins suggest possible associations with breast cancer and support additional research on those compounds.

Among chemicals identified in toxicologic research as relevant to breast cancer, many have not been investigated in humans. The research team emphasized the need to develop better exposure assessment methods to fill this gap. In the interim, the researchers say, weaknesses in the epidemiologic literature argue for greater reliance on toxicologic studies to develop national policies to reduce chemical exposures that may be associated with breast cancer. The researchers also noted that the substantial research progress since 2002 suggests that the investigation of environmental pollutants will lead to strategies to reduce breast cancer risk.
See Science Review • environmental pollutants
Review Article

Genetic Variability
See Science Review • genetic variability

Physical Activity
The evidence is now substantial that lack of physical activity—along with postmenopausal weight gain, high waist-to-hip ratio, and other body-size factors—is associated with a higher breast cancer risk. Public health initiatives and research to identify the most effective strategies for promoting physical activity should be breast cancer priorities.
See Science Review • physical activity
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Abbreviations
 

Mammary Carcinogens Review Database

The Mammary Carcinogens Review Database reveals that among the 216 compounds identified as causing breast tumors in animals, 73 have been present in consumer products or as contaminants in food, 35 are air pollutants, and 25 have been associated with occupational exposures affecting more than 5,000 women a year. Twenty-nine of the compounds are produced in the United States in large quantities, often exceeding one million pounds a year. The database includes references to 900 studies.

Animal studies guide the development of new pharmaceuticals by testing for effectiveness and safety before the drugs are tested in humans. For commercial chemicals and pollutants, animal studies are currently the primary means of identifying carcinogens and guiding exposure reduction to prevent environmental cancers.

For each chemical listed, the database includes its carcinogenic potential, its ability to cause gene mutations, the exposure to it in the general population and for women at work, and other characteristics of use, sources, and regulation. This information is crucial for regulators to consider in decisions about limiting human exposure and for manufacturers to evaluate in reformulating products and re-engineering processes to avoid suspect chemicals. It is also valuable for epidemiologists to identify new chemicals, exposure scenarios, and exposed populations for breast cancer studies.

Refer to the review and commentary publications for a description of methods, conclusions, and recommendations.

Criteria for Chemicals Included in the Database

The Mammary Carcinogens Review Database includes information on 216 chemicals that increased mammary gland tumors in animal studies conducted by the U.S. National Toxicology Program (NTP) or included in the International Agency for Research on Cancer (IARC) Monographs, the 11th Report on Carcinogens (11th ROC), the Carcinogenic Potency Database (CPDB), or the Chemical Carcinogenesis Research Information System (CCRIS) database.

The research team used the following criteria in choosing which chemicals to include in the database:

  • CPDB: We selected all chemicals with at least one study that reported an increase in mammary gland tumors.
  • IARC Monograph summaries: We searched for “mammary” and included those chemicals that increased mammary gland tumors.
  • NTP Technical Reports: We included all the chemicals from the NTP web page entitled, “Chemicals Associated with Site-Specific Tumor Induction in Mammary Gland,” which draws from the Technical Reports collection. We also used the search term “mammary” to select chemicals that increased mammary tumors in the NTP Study Reports Collection under “Abstracts” and “Target Sites in 2-Year Studies.”
  • NTP 11th Report on Carcinogens: We included chemicals that were returned after a search for “mammary” and that were associated with increased mammary tumors.
  • CCRIS: We selected by the search term “mammary” and those that had positive results in the “Carcinogenicity Studies” section.

This list may be incomplete because most chemicals—including most in common use—have never been tested for their carcinogenicity in animals, and so it is not known whether they might cause mammary gland tumors or other tumors. The chemicals listed here vary in the strength of the evidence that they are human carcinogens. To aid the user in evaluating the strength of evidence, we have compiled references and links to the sources that identified each chemical as a mammary gland carcinogen.

Database development is ongoing, and information is more complete for some chemicals than for others. For 45 priority chemicals with current or past widespread exposure, we have assembled complete citations for studies reporting mammary gland tumors and for most of those studies that did not report mammary gland tumors. For a smaller subset of chemicals, we have extracted experimental details from the original studies to examine the strength of the evidence more fully. For 11 chemicals that have been the subject of recent risk assessments—ethylene oxide, methylene chloride, vinylidene chloride, MX (3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone), and several polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs—we also reviewed governmental and nongovernmental risk assessments from a range of agencies and groups. For a detailed description of methods, please consult the accompanying article.

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Key References
Abbreviations
 

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