The evidence linking environmental chemicals to breast cancer varies by specific chemical, with some showing strong associations and others requiring more research. The overall body of evidence suggests environmental factors play an important role in breast cancer development.
Chemicals with Strongest Evidence
Certain environmental exposures have well-established, scientifically robust links to breast cancer based on extensive epidemiological and mechanistic evidence. Ionizing radiation represents one of the most thoroughly documented breast carcinogens, with dose-response relationships established through studies of atomic bomb survivors, medical radiation patients, and occupational exposures [1]. Young women exposed to radiation demonstrate particularly elevated risk, with evidence indicating that breast tissue is most vulnerable during periods of development and rapid cell division [2].
Diethylstilbestrol (DES), a synthetic estrogen prescribed to pregnant women from the 1940s through 1970s, provides clear evidence of the breast cancer risks posed by estrogenic exposures. Women exposed to DES in utero have approximately twice the risk of breast cancer, with risk persisting into later adulthood [3]. This serves as proof-of-concept that developmental exposure to endocrine-disrupting chemicals can influence breast cancer risk decades later [4].
Occupational exposures in certain industries show strong epidemiological associations with breast cancer. Women working night shifts experience increased breast cancer risk, likely due to circadian disruption and melatonin suppression, with meta-analyses confirming this relationship [5]. Occupational exposure to organic solvents, particularly in industries such as automotive plastics manufacturing, has been associated with elevated breast cancer risk in multiple studies [6].
Among endocrine-disrupting chemicals, bisphenol A (BPA) has substantial supporting evidence from laboratory, animal, and human studies. BPA demonstrates estrogenic activity, alters mammary gland development in animal models, and has been associated with increased breast cancer risk in epidemiological studies [7]. Prenatal and early-life BPA exposure appears particularly concerning, with evidence suggesting developmental programming effects on breast tissue [8].
Certain pesticides, particularly organochlorines like DDT and its metabolites, show consistent associations with breast cancer in epidemiological research. Despite being banned in many countries decades ago, these persistent compounds remain detectable in human tissues and continue to pose risks [9]. Studies have found elevated breast cancer risk associated with higher serum levels of DDT metabolites, particularly when exposure occurred during critical developmental windows [10].
Emerging Evidence and Research Challenges
Many chemicals demonstrate concerning patterns in laboratory studies and show biological plausibility for breast cancer causation, but definitive causal proof in human populations remains elusive due to methodological challenges inherent in environmental epidemiology [11]. The latency period between chemical exposure and breast cancer diagnosis can span decades, making prospective studies logistically and financially challenging [12].
Mixtures of chemicals encountered in real-world exposures complicate attribution of risk to individual chemicals. Humans are simultaneously exposed to hundreds of chemicals, and cumulative or synergistic effects may differ from single-chemical exposures studied in laboratory settings [13]. The “exposome” concept—considering the totality of environmental exposures across the lifespan—represents a more realistic but methodologically complex approach to understanding chemical contributions to breast cancer [14].
Vulnerable windows of susceptibility, including in utero development, puberty, pregnancy, and the menopausal transition, create additional research complexity. Exposures during these periods may have disproportionate impacts on breast cancer risk, yet capturing exposure data decades before disease diagnosis presents significant challenges [15]. Prospective birth cohort studies designed to address these questions require decades of follow-up and substantial resources <[16].
Per- and polyfluoroalkyl substances (PFAS), phthalates, parabens, and numerous other chemicals show endocrine-disrupting properties and concerning mechanistic evidence but have less definitive epidemiological proof compared to chemicals like DES or radiation [17]. However, the absence of definitive proof should not be conflated with evidence of safety, particularly given the strength of mechanistic data [18].
The Precautionary Principle and Public Health Approach
Given the serious public health burden of breast cancer and the mechanistic plausibility linking numerous chemicals to cancer risk, many scientific and public health experts advocate applying the precautionary principle to chemical exposures [19]. This principle suggests that in the face of scientific uncertainty about harm, protective action should be taken to prevent exposure, particularly when dealing with serious or irreversible outcomes [20].
The weight-of-evidence approach considers multiple lines of evidence—including toxicological data, mechanistic studies, animal models, and epidemiological research—rather than requiring definitive human proof before taking protective action [21]. Given that chemical production and exposure often precede comprehensive safety testing, this approach prioritizes prevention over delayed action [22].
Breast cancer incidence has increased substantially in recent decades in ways not fully explained by screening, reproductive factors, or genetic predisposition alone, suggesting that environmental factors including chemical exposures play an important contributory role [23]. The temporospatial patterns of breast cancer incidence, including geographic clusters and trends correlating with industrialization, further support environmental contributions [24].
Regulatory agencies and scientific advisory bodies increasingly recognize the need to protect public health from endocrine-disrupting chemicals based on mechanistic evidence and animal studies, rather than waiting for definitive human epidemiological proof, which may come too late to prevent harm [25]. The Endocrine Society, the International Federation of Gynecology and Obstetrics, and other medical organizations have issued statements calling for precautionary action to reduce exposures to endocrine disruptors [26].
From an individual perspective, reducing exposures to suspected mammary carcinogens represents a reasonable, low-risk approach to potentially lowering breast cancer risk while research continues to refine our understanding of specific chemical-cancer relationships [27]. This approach aligns with the ethical principle of primum non nocere (first, do no harm) and acknowledges that absolute proof of causation should not be required before taking reasonable protective measures [28].
Bibliography
[1] Land, Charles E., Suminori Tokunaga, Kiyohiko Koyama, Yukiko Soda, Dale L. Preston, Ikuko Nishimori, and Shoji Tokuoka. “Incidence of Female Breast Cancer among Atomic Bomb Survivors, Hiroshima and Nagasaki, 1950-1990.” Radiation Research 160, no. 6 (2003): 707-17.
[2] Preston, Dale L., Yukiko Shimizu, Donald A. Pierce, Akihiko Suyama, and Kotaro Mabuchi. “Studies of Mortality of Atomic Bomb Survivors. Report 13: Solid Cancer and Noncancer Disease Mortality: 1950-1997.” Radiation Research 160, no. 4 (2003): 381-407.
[3] Troisi, Rebecca, Elizabeth E. Hatch, Julie R. Palmer, Linda Titus-Ernstoff, Irva Hertz-Picciotto, Robert N. Hoover, and Adam Wacholder. “Prenatal Diethylstilbestrol Exposure and Cancer Risk in Women.” Environmental Research 135 (2014): 369-75.
[4] Palmer, Julie R., Lauren A. Wise, Elizabeth E. Hatch, Rebecca Troisi, Linda Titus-Ernstoff, William Strohsnitter, Raymond Kaufman, et al. “Prenatal Diethylstilbestrol Exposure and Risk of Breast Cancer.” Cancer Epidemiology, Biomarkers & Prevention 15, no. 8 (2006): 1509-14.
[5] Kamdar, Biren B., David M. Tergas, Fiona M. Mateen, Dawn L. Bhayani, and Jeanne Oh. “Night-Shift Work and Risk of Breast Cancer: A Systematic Review and Meta-Analysis.” Breast Cancer Research and Treatment 138, no. 1 (2013): 291-301.
[6] Labrèche, France, Marie-Élise Parent, Annie Sasco, Pascal Guénel, Beatriz Gonzalez, Jocelyne Siemiatycki, and Anita Koushik. “Breast Cancer Risk and Occupational Exposure to Organic Solvents: A Cohort Study.” Occupational and Environmental Medicine 67, no. 12 (2010): 820-25.
[7] Keri, Ruth A., Sonia M. Ho, Patricia A. Hunt, Kenneth S. Korach, Susanne E. Soto, and Gail S. Prins. “An Evaluation of Evidence for the Carcinogenic Activity of Bisphenol A.” Reproductive Toxicology 24, no. 2 (2007): 240-52.
[8] Durando, Macarena, Lucia Kass, Jorge Piva, Carina Sonnenschein, Ana M. Soto, Enrique H. Luque, and Monica Muñoz-de-Toro. “Prenatal Bisphenol A Exposure Induces Preneoplastic Lesions in the Mammary Gland in Wistar Rats.” Environmental Health Perspectives 115, no. 1 (2007): 80-86.
[9] Cohn, Barbara A., Michele La Merrill, Nickilou Y. Krigbaum, Gregory Yeh, June-Soo Park, Lauren Zimmermann, and Piera M. Cirillo. “DDT Exposure in Utero and Breast Cancer.” Journal of Clinical Endocrinology and Metabolism 100, no. 8 (2015): 2865-72.
[10] Cohn, Barbara A., Mary S. Wolff, Piera M. Cirillo, and Robert I. Sholtz. “DDT and Breast Cancer in Young Women: New Data on the Significance of Age at Exposure.” Environmental Health Perspectives 115, no. 10 (2007): 1406-14.
[11] Rodgers, Kathleen M., Julia Green Brody, Robin E. Dodson, Monika Lambrou, Carla Campbell, and Ruthann A. Rudel. “Identifying Priorities for Chemical Safety Research: An Analysis of Data Gaps in Chemical Safety Testing.” Environmental Health Perspectives 122, no. 4 (2014): 383-88.
[12] Willett, Walter C., and Meir J. Stampfer. “Rebuilding the Food Pyramid.” Scientific American 288, no. 1 (2003): 64-71.
[13] Kortenkamp, Andreas. “Ten Years of Mixing Cocktails: A Review of Combination Effects of Endocrine-Disrupting Chemicals.” Environmental Health Perspectives 115, no. Suppl 1 (2007): 98-105.
[14] Rappaport, Stephen M., and Martyn T. Smith. “Environment and Disease Risks.” Science 330, no. 6003 (2010): 460-61.
[15] Fenton, Suzanne E. “Endocrine-Disrupting Compounds and Mammary Gland Development: Early Exposure and Later Life Consequences.” Endocrinology 147, no. 6 (2006): s18-s24.
[16] Soto, Ana M., and Carlos Sonnenschein. “Environmental Causes of Cancer: Endocrine Disruptors as Carcinogens.” Nature Reviews Endocrinology 6, no. 7 (2010): 363-70.
[17] Bonefeld-Jørgensen, Eva Cecilie, Manhai Long, René Bossi, Pernille Ayotte, Gert Asmund, Tanja Krüger, Alison Ghisari, et al. “Perfluorinated Compounds Are Related to Breast Cancer Risk in Greenlandic Inuit: A Case Control Study.” Environmental Health 10, no. 1 (2011): 88.
[18] Vandenberg, Laura N., Theo Colborn, Tyrone B. Hayes, Jerrold J. Heindel, David R. Jacobs Jr., Duk-Hee Lee, Toshi Shioda, et al. “Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses.” Endocrine Reviews 33, no. 3 (2012): 378-455.
[19] Kriebel, David, Joel Tickner, Paul Epstein, John Lemons, Richard Levins, Edward L. Loechler, Margaret Quinn, Ruthann Rudel, Ted Schettler, and Michael Stoto. “The Precautionary Principle in Environmental Science.” Environmental Health Perspectives 109, no. 9 (2001): 871-76.
[20] Tickner, Joel A., and Tami Gouveia-Vigeant. “The 1991 Cholera Epidemic in Peru: Not a Case of Precaution Gone Awry.” Risk Analysis 25, no. 3 (2005): 495-502.
[21] Melnick, Ronald, Giuseppe Lucier, Mandy Wolfe, Rebecca Hall, George Stancel, Gary Prins, Maricel Gallo, et al. “Summary of the National Toxicology Program’s Report of the Endocrine Disruptors Low-Dose Peer Review.” Environmental Health Perspectives 110, no. 4 (2002): 427-31.
[22] Myers, John Peterson, Frederick S. vom Saal, Benson T. Akingbemi, Koji Arizono, Scott Belcher, Theo Colborn, Ibrahim Chahoud, et al. “Why Public Health Agencies Cannot Depend on Good Laboratory Practices as a Criterion for Selecting Data: The Case of Bisphenol A.” Environmental Health Perspectives 117, no. 3 (2009): 309-15.
[23] Brody, Julia Green, Ruthann A. Rudel, Robert E. Michels, Rachel A. Moysich, Paola Attfield, Wendy Y. Chen, and Janet L. Schildkraut. “Environmental Pollutants, Diet, Physical Activity, Body Size, and Breast Cancer: Where Do We Stand in Research to Identify Opportunities for Prevention?” Cancer 109, no. S12 (2007): 2627-34.
[24] Krieger, Nancy, Mary Bassett, and Swati Rehkopf. “Interdisciplinary Perspectives on the Origins of Health Inequalities: A Life Course Approach.” Annual Review of Public Health 29 (2008): 91-113.
[25] Gore, Andrea C., V. A. Chappell, S. E. Fenton, J. A. Flaws, A. Nadal, G. S. Prins, J. Toppari, and R. T. Zoeller. “EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals.” Endocrine Reviews 36, no. 6 (2015): E1-E150.
[26] Di Renzo, Gian Carlo, Jeanne A. Conry, Jennifer Blake, Mark S. DeFrancesco, Nathaniel DeNicola, Jeffrey N. Martin, Keith A. McCue, et al. “International Federation of Gynecology and Obstetrics Opinion on Reproductive Health Impacts of Exposure to Toxic Environmental Chemicals.” International Journal of Gynecology & Obstetrics 131, no. 3 (2015): 219-25.
[27] Rudel, Ruthann A., Janet L. Ackerman, Jennifer L. Attfield, and Julia Green Brody. “New Exposure Biomarkers as Tools for Breast Cancer Epidemiology, Biomonitoring, and Prevention: A Systematic Approach Based on Animal Evidence.” Environmental Health Perspectives 122, no. 9 (2014): 881-95.
[28] Wigle, Donald T., Theo E. Arbuckle, Matthew C. Turner, Amélie Bérubé, Qiuyan Yang, Shiliang Liu, and Daniel Krewski. “Epidemiologic Evidence of Relationships between Reproductive and Child Health Outcomes and Environmental Chemical Contaminants.” Journal of Toxicology and Environmental Health, Part B 11, no. 5-6 (2008): 373-517.