Litigation Guides

Roundup Weed Killer

Glyphosate, a popular herbicide known by trade names like Roundup, has been linked to non-Hodgkin's lymphoma and is under investigation for its potential connection to breast cancer, with studies indicating its estrogen-like effects in breast tissue cells. Despite some evidence suggesting a risk, the current understanding of glyphosate's link to breast cancer remains speculative, emphasizing the need for further in vivo studies to confirm its effects on human health.

Medically Reviewed

01

What is Glyphosate?

Glyphosate, or N-(phosphonomethyl) glycine, more commonly known by its trade names Roundup and Ranger Pro, are popular herbicides used throughout the United States. Glyphosate, which is an endocrine disrupting chemical, and its major breakdown product (AMPA), are found in soil, air, and water, but at levels that are considered below the Acceptable Daily Intake levels by some global regulatory agencies.1

However, Roundup and Ranger Pro have been the subject of many lawsuits (and billions of dollar in settlements) for its link with non-Hodgkin’s lymphoma (and the allegation that its manufacturer, Monsanto, was aware of the link). There are now some studies indicating a link between glyphosate and breast cancer, although other studies are less determinative.

Person using weed killer
02

Timeline of Glyphosate’s Usage and Risks

  • 1975 - Glyphosate is first approved for use in the U.S. to kill crop-damaging weeds2
  • 1992-2009 - Glyphosate usage increased nearly 16-fold
  • 2015 - The International Agency for Research on Cancer, a division of the International Agency for Research on Cancer, concludes that glyphosate is probably carcinogenic to humans, finding a link with non-Hodgkin’s lymphoma (NHL)3
  • 2020 - The U.S. Environmental protection Agency (EPA) issued an interim decision determining that there are no risks of concern and glyphosate is unlikely to be a human carcinogen when used in accordance with its label4
  • 2022 - The EPA withdrew its 2020 interim registration review decision, after challenged in federal court
03

Glyphosate’s Link to Non-Hodgkin Lymphoma

A review of nine epidemiologic studies on NHL and glyphosate found that glyphosate exposure from agricultural applications imparts “no excess risk of deleterious health effects, even for sensitive subpopulations.”5

In contrast, a meta-analysis of five studies reached the opposite conclusion, finding that the results suggest a compelling link between glyphosate-based herbicides and an increased risk for NHL.6

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04

Notable Studies of Glyphosate’s Potential Link to Breast Cancer

  • In February 2023, a study was published that suggested high concentrations of glyphosate induces estrogen-like effects through an estrogen receptor alpha ligand binding site-dependent mechanism, leading to certain cellular responses.7 Specifically, the exposure induces estrogen-like effects in breast tissue cells that can cause cellular proliferation, and then in turn, could lead to the development or progression of breast cancer. However, the mechanism is not fully understood and the study was conducted in a laboratory setting, with the authors concluding that “further studies in animal models must confirm these effects on organ systems.”
  • Other authors have found that in vitro studies have revealed that glyphosate causes oxidative stress, induces DNA damage, alters estrogen pathways, and disturbs brain functions. It was also implicated in the development of various cancer types, including breast cancer.8
  • Another study of urinary concentrations and breast cancer development in Hawaiian women found a 4.5-fold increase in breast cancer risk with the highest concentrations of urinary AMPA (a breakdown product of glyphosate found in soil), identifying an association between breast cancer and glyphosate.9
  • A study on glyphosate and two other insecticides found that all three displayed endocrine-disrupting activity. Despite no definitive conclusion regarding the outcomes on mammary gland development, the results raise a concern of possible adverse effects, especially in vulnerable population groups such as children.10
  • A study of seven compounds, including glyphosate, indicated that the chemical can generate a genetic mutation predisposing a cancer risk by affecting DNA methylation/demethylation reactions.11
  • Glyphosate-mediated DNA hypomethylation is associated with TET3 over-expression, although genetic alternations in TET3 genes are rare in breast cancer.12
  • A study of how estrogens and estrogen-disrupting chemicals, such as glyphosate, modulate mammary gland metabolism, shows that estrogens reprogrammed these glands differently when growing in 2-and 3-dimensional models. Estrogen-disrupting chemicals also altered bioenergetic fluxes. As there was more sensitivity to low concentrations of estrogen-disrupting chemicals, they make a key model in screening for the impact of various environmental pollutants. These chemicals interfered with the regulation of estrogen target genes and the expression of metabolic genes in organoids. Results also suggest that they act through modulation of the estrogen receptor activity.13
  • Other studies found glyphosate promoted proliferation of human breast cancer cells.14,15
  • Cells exposed to Roundup and AMPA in low concentrations indicated gene expression changes, suggesting the compounds can cause cellular damage at low doses in short periods of time.16
  • Glyphosate’s effects appeared only in human hormone-dependent breast cancer cells, not hormone-independent breast cancer.
05

Does Roundup Cause Breast Cancer?

A review of case reports do not indicate any cases of breast cancer in a patient with a history of exposure to glyphosate. With the exception of one of the above studies, there is no in vivo data (outside of a laboratory) confirming the relationship between glyphosate and the development of breast cancer in humans.

No case report was identified showing any relationship between glyphosate exposure and the subsequent development of breast cancer. Current studies show the link between glyphosate and breast cancer is speculative, based on its endocrine disrupting activity and the effect it has on estrogen-sensitive mammary cells in vitro.

06

Works Cited

1.

Benbrook CM. Trends in glyphosate herbicide use in the United States and globally. Environ Sci Eur. 2016;28(1):3. URL

2.

Acquavella J. Epidemiologic studies of glyphosate and non-Hodgkin's lymphoma: a review with consideration of exposure frequency, systemic dose, and study quality. Glob Epidemiol. 2023;5:10010. URL

3.

Weisburger DD. A review and update with perspective of evidence that the herbicide glyphosate (Roundup) is a cause of non-Hodgkin lymphoma. Clin Lymphoma Myeloma Leukemia. 2021;21(9):621–630. URL

4.

United States Environmental Protection Agency. Glyphosate. September 2023. Accessed October 30, 2023 URL

5.

Acquavella J. Epidemiologic studies of glyphosate and non-Hodgkin's lymphoma: a review with consideration of exposure frequency, systemic dose, and study quality. Glob Epidemiol. 2023;5:10010. URL

6.

Zhang L, Rana I, Shaffer RM, Taioli E, Sheppard L. Exposure to glyphosate-based herbicide and risk for non-Hodgkin lymphoma: a meta-analysis and supporting evidence. Mut Res-Rev Mut Res. 2019;781:186-206. URL

7.

Muñoz JP, Araya-Osorio R, Mera-Adasme R, Calaf GM. Glyphosate mimics 17β-estradiol effects promoting estrogen receptor alpha activity in breast cancer cells. Chemosphere. 2023;313:137201. URL

8.

Bukowska B, Woźniak E, Sicińska P, Mokra K, Michalowicz J. Glyphosate disturbs various epigenetic processes in vitro and i vivo − a mini review. Sci Total Environ. 2022;851:158259. URL

9.

Franke AA, Li X, Shvetsov YB, Lai JF. Pilot study on the urinary excretion of the glyphosate metabolite aminomethylphosphonic acid and breast cancer risk: the Multiethnic Cohort Study. Environ Pollut. 2021;277:116848. URL

10.

Coppola L, Tait S. Fabbrizi E, Perugini M, La Rocca C. Comparison of the toxicological effects of pesticides in non-tumorigenic MCF-12A and tumorigenic MCF-7 human breast cells. Int J Envir Res Public Health. 2022;19:4453. URL

11.

Courant F, Bougra-Cartron G, Abadie C, Frenel J-S, Cartron P-F. Modulation of DNA methylation/demethylation reactions induced by nutraceuticals and pollutants of exposome can promote a C > T mutation in the breast cancer predisposing gene PALB2. Epigenomes. 2022;6:32. URL

12.

Duforestel M, Nadaradjane A, Bougras-Cartron G, Briand J, Olivier C, Frenel J-S, et al. Glyphosate primes mammary cells for tumorigenesis by reprogramming the epigenome in a TET3-dependent manner. Front Genet. 2019;10:885. URL

13.

Lacouture A, Breton Y, Weidmann C, Goulet S-M, Germain L, Pelletier M, et al. Estrogens and endocrine-disrupting chemical differentially impact the bioenergetic fluxes of mammary epithelial cells in two- and three-dimensional models. Environ Int. 2023;179:108132. URL

14.

Mesnage R, Phedonos A, Biserni M, Arno M, Balu S, Corton JC, et al. Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents. Food Chem Toxicol. 2017;708:30-42. URL

15.

Sritana N, Suriyo T, Kanitwithayanun J, Songvasin BH, Thiantanawat A, Satayavivad J. Glyphosate induces growth of estrogen receptor alpha positive cholangiocarcinoma RoundUp and Breast Cancer | 15 cells via non-genomic estrogen receptor/ERK1/2 signaling pathway. Food Chem Toxicol. 2018;118:595-607. URL

16.

Stur E, Aristizabal-Pachon AF, Peronni KC, Agostini LP, Waigel S, Chariker J, et al. Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019;14(7):e0219610. URL

About the authors

Wendy Ketner, M.D.

Wendy Ketner, M.D.

Dr. Wendy Ketner is a distinguished medical professional with a comprehensive background in surgery and medical research. Currently serving as the Senior Vice President of Medical Affairs at the Expert Institute, she plays a pivotal role in overseeing the organization's most important client relationships. Dr. Ketner's extensive surgical training was completed at Mount Sinai Beth Israel, where she gained hands-on experience in various general surgery procedures, including hernia repairs, cholecystectomies, appendectomies, mastectomies for breast cancer, breast reconstruction, surgical oncology, vascular surgery, and colorectal surgery. She also provided care in the surgical intensive care unit.

Her research interests have focused on post-mastectomy reconstruction and the surgical treatment of gastric cancer, including co-authoring a textbook chapter on the subject. Additionally, she has contributed to research on the percutaneous delivery of stem cells following myocardial infarction.

Dr. Ketner's educational background includes a Bachelor's degree from Yale University in Latin American Studies and a Doctor of Medicine (M.D.) from SUNY Downstate College of Medicine. Moreover, she is a member of the Board of Advisors for Opollo Technologies, a fintech healthcare AI company, contributing her medical expertise to enhance healthcare technology solutions. Her role at Expert Institute involves leveraging her medical knowledge to provide insights into legal cases, underscoring her unique blend of medical and legal acumen.

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