Researchers at Tufts University School of Medicine and Boston University discovered that a low-concentration mixture of common bisphenols—BPA, BPS, and BPF—disrupts normal breast tissue development in lab-grown human organoids. Published in the Proceedings of the National Academy of Sciences, the findings link these environmental chemical exposures to molecular patterns found in invasive lobular carcinoma.
Tufts University and Boston University Organoid Experiment
To investigate how environmental exposures affect mammary gland development, scientists utilized three-dimensional cell models known as organoids. These structures derive from breast tissue donated by 13 healthy young women, incorporating multiple cell types capable of replicating specific aspects of human breast tissue growth. The organoids developed over a period of about three weeks while researchers exposed them to various individual substances and chemical mixtures. The tested agents included endocrine disruptors, metabolism-altering compounds, and suspected carcinogens.
While individual chemicals triggered relatively few alterations in the tissue models, a combination of three common bisphenols produced the most striking results. Exposure to a mixture of BPA, BPS, and BPF at very low concentrations—levels comparable to those detected in human blood and urine—interrupted normal development across organoids from most donors.
We intentionally used concentrations of chemicals that were relevant to real-world exposure rather than the very high doses sometimes used in toxicology studies. We also tested a mixture of these because people are typically exposed to multiple chemicals at the same time.
Charlotte Kuperwasser, professor of developmental, molecular, and chemical biology at Tufts University School of Medicine
Comparison to Invasive Lobular Carcinoma Profiles
After observing the developmental disruption, the research team compared the molecular changes found in the treated organoids with data from human breast cancers. The exposure-associated molecular pattern aligned most strongly with patient data for invasive lobular carcinoma, a form of breast disease that may not cause a detectable lump and can be difficult to detect with a mammogram.
Study authors emphasized that the investigation does not establish that these chemicals cause cancer or prove a direct mechanism linking the observed molecular changes to disease. Instead, the research highlights a novel experimental approach for studying how environmental factors influence normal human tissue prior to the onset of malignancy.
Historically, we have thought about cancer risk largely in terms of inherited mutations, lifestyle factors, and exposures that directly damage DNA. These findings raise another possibility: Environmental exposures may subtly alter how normal tissues develop, leaving behind molecular changes that do not cause cancer by themselves but may make the tissue more permissive to cancer many years later.
Charlotte Kuperwasser, Tufts University School of Medicine
Biological Records and Future Research Directions
The persistent molecular changes observed in the laboratory models could eventually function as a biological record, operating similarly to a scar of past exposure. If future clinical studies validate these markers in humans, such biological records might eventually assist in identifying individuals at elevated risk and guide more targeted or earlier screening procedures.
The study was supported by Find The Cause Breast Cancer Foundation, with Meadow Parrish and Meloryn Seraj serving as co-first authors. Investigators noted that subsequent research involving broader chemical mixtures and larger, more diverse donor groups will be necessary to determine how widely these cellular findings apply to human populations.