A breast tissue organoid that has been artificially colored. Credit: The Kuperwasser Lab
‘BPA-Free’ Chemicals Plus BPA Disrupt Lab-Grown Breast Tissue
In A Nutshell
- Three bisphenols tested alone at low doses had no significant effect on lab-grown breast tissue.
- Combined, they disrupted tissue growth and changed more than 1,100 genes.
- Gene and DNA changes overlapped with patterns in invasive lobular carcinoma.
- Lab results cannot show that bisphenols cause breast cancer.
Three chemicals found in everyday plastics had no significant effect on lab-grown human breast tissue when tested one at a time at low doses. Combined at those same doses, they disrupted how the tissue developed and switched on genes tied to invasive lobular carcinoma, a breast cancer type whose rates have more than doubled since 1975.
Those chemicals are BPA, BPS, and BPF, all members of the bisphenol family used in plastics. BPS and BPF are close relatives of BPA, and products labeled “BPA-free” often use one of them instead. Researchers at Tufts University School of Medicine and Boston University tested the trio together and reported the results in the Proceedings of the National Academy of Sciences.
That matters because safety studies often test one chemical at a time, while national survey data cited in the paper show that more than 95 percent of Americans carry detectable levels of several hormone-disrupting chemicals at once. Real life delivers a mixture of exposures, not one ingredient at a time. The experiment cannot show that bisphenols cause breast cancer, and the authors say so.
Low-Dose BPA Mixture Disrupted Breast Tissue Grown From Healthy Donors
Cells for the main experiment came from six healthy women, ages 17 to 31, who had breast reduction surgery. Placed in a gel designed to mimic the inside of a breast, the cells organized into tiny branching structures that resemble the milk ducts and milk-producing clusters of real breast tissue. Researchers note that developing breast tissue is especially sensitive to outside influences.
Before focusing on bisphenols, the team screened 17 chemicals, and many knocked tissue growth off course in different ways. Some reduced how many structures formed, while others changed their size or branching. At that screening dose, which was higher than the one used later, several individual bisphenols did alter tissue size and branching.
For the main test, the researchers picked a low dose based on bisphenol levels found in Americans’ urine, rather than unusually high laboratory doses. Each bisphenol was also tested alone at that dose for comparison. With all three together, five of the six donors’ tissue formed fewer structures than untreated samples. Two donors’ tissue grew milk-producing clusters too early, and one produced abnormal clumps. Donors responded differently, so the team built a scoring system that rolls several signs of disruption into one number. Every donor showed at least one sign.
Combined Bisphenols Rewired More Than 1,100 Genes in Breast Tissue
Compared with untreated samples, exposed tissue had 712 genes turned up and 469 turned down. Genes that break down and rebuild the tissue’s scaffolding became more active, while genes that give breast cells their identity and hold neighboring cells together quieted down. In plain terms, orderly cells loosened their grip on one another and started acting more like mobile, shape-shifting cells, a change linked to cancer in earlier research. Two genes ranked among the most strongly turned up in all six donors’ tissue, even though the donors otherwise responded in different ways.
BPA Mixture’s Gene Pattern Showed Up More in Invasive Lobular Carcinoma
To see whether the pattern appears in real cancers, the team scored tumors in large public databases for how strongly they showed it. Scores ran higher in hormone-sensitive tumors, and higher in invasive lobular carcinoma than in invasive ductal carcinoma, the more common type. Within one tumor subtype, the paper describes the gap as “modest but reproducible.”
A catalog of more than 600,000 cells from 138 patients showed the pattern concentrated in a small group of tumor cells and certain supportive cells, rather than spread evenly across all tumors. Invasive lobular carcinoma grows through breast tissue in a diffuse, spread-out pattern, and it is rising three times faster than other breast cancers, with cases climbing among women under 50 as well, according to figures the paper cites. The experiment does not explain that trend, but the overlap gives researchers a lead to chase.
BPA Mixture Altered DNA Tags That Also Differ in Breast Tumors
Exposed tissue showed changes at thousands of spots in the chemical tags on its DNA, which work like dimmer switches for genes without altering the genetic code itself. Those measurements came right after continuous exposure, and the study did not test whether the changes persisted once the chemicals were removed.
Compared against data from 784 tumors and 97 samples of normal-looking tissue beside tumors, the bisphenol-linked DNA pattern scored lower in tumors than in the neighboring tissue. Normal-looking tissue near tumors may carry hidden molecular changes, though the authors note their data cannot show that the exposure caused them.
A separate test paired each bisphenol with a known cancer-causing pollutant. Adding any one of the three raised tissue disruption beyond what the pollutant caused alone, and each pairing left its own DNA-tag pattern.
Nothing here shows that “BPA-free” products raise cancer risk, since chemicals rather than products were tested. Still, a chemical that looks harmless alone can behave differently in combination, and safety testing should reflect the combinations people actually encounter.
Disclaimer: This article reports on a laboratory study and is for informational purposes only. It is not medical advice. Anyone with concerns about breast cancer risk or chemical exposure should talk with a qualified health care professional.
Paper Notes
Limitations
Findings establish an association, not a cause. The researchers write that the data “do not demonstrate a direct causal relationship between exposure and tumor initiation or subtype-specific progression,” and that normal-looking tissue beside tumors cannot be tied to the modeled exposure. The main bisphenol experiment used tissue from only six donors, and results varied between donors and even between individual tissue samples from the same donor. A scoring system was built to handle that variability, but larger and more diverse donor groups are needed. DNA measurements were taken at the end of continuous exposure, so persistence after exposure ended was not tested, and DNA samples were pooled across donors. Only one or two genes could be compared across the DNA and gene-activity datasets, which prevented a firm link between the two. The study also did not determine whether the effects work through estrogen receptors, other routes, or both, and future work should test more chemicals and mixtures. Tumor comparisons relied on existing databases rather than new patient samples.
Funding and Disclosures
FTC Breast Cancer Foundation funding supported the research (to S.M. and C.K.). The authors declare no competing interest. The acknowledgments thank members of the Find The Cause (FTC) Consortium for helpful discussions.
Publication Details
Meadow Parrish, Meloryn Seraj, Helia Nikoueian, Nicole Traugh, Andrew Chen, Piyush B. Gupta, Stefano Monti, and Charlotte Kuperwasser wrote the paper, titled “Environmental chemical mixtures reprogram mammary epithelial development to epigenetic states associated with breast cancer.” Parrish and Seraj contributed equally, and Kuperwasser (Tufts University School of Medicine, [email protected]) is the corresponding author. Affiliations include Tufts University School of Medicine and the Boston University Chobanian and Avedisian School of Medicine. It was published October 15, 2026, in the Proceedings of the National Academy of Sciences (PNAS), Volume 123, Number 42, e2613054123, and edited by Myles Brown of Dana-Farber Cancer Institute. The article is open access. DOI: 10.1073/pnas.2613054123 (https://doi.org/10.1073/pnas.2613054123). Sequencing data are deposited in the Gene Expression Omnibus under GSE329431, GSE327552, and GSE274346.







