NIH study links two 'forever chemicals' to sharply higher risk of aggressive breast cancer

A large NIH study has found that women with the highest blood levels of two widely used synthetic chemicals face dramatically higher rates of an aggressive form of breast cancer — one that does not respond to the hormone-blocking therapies used to treat most breast cancers and carries a higher likelihood of early recurrence and poorer survival.

Blood samples collected before diagnosis from 1,609 women who subsequently developed breast cancer, along with samples from a comparison group of 2,269 women who did not, formed the basis of the study, which was published in the Journal of Clinical Oncology. To search for connections between exposure levels and breast cancer risk by tumor type, researchers took measurements of 17 PFAS — per- and polyfluoroalkyl substances, a family of synthetic chemicals that persist in the environment and the human body for years.

The clearest signal emerged for estrogen receptor-negative breast cancer. Women in the highest exposure group for perfluorooctanoic acid (PFOA) had a 67% higher rate of ER-negative breast cancer compared to those in the lowest group. For perfluorooctanesulfonic acid (PFOS), the highest exposure group had a 93% higher rate. Crucially, no consistent link appeared between either chemical and breast cancer overall, or with the more common ER-positive tumors.

We know very little about risk factors for ER-negative tumors. We already know these compounds have been classified as known or possible carcinogens by the International Agency for Research on Cancer, but it is important to add to the evidence base for breast cancer specifically to help improve the understanding of the range of health outcomes these compounds may be contributing to.— Alexandra White, PhD, MSPH, NIH Stadtman Investigator and leader of the National Institute of Environmental Health Sciences' Environment and Cancer Epidemiology Group

White was careful to frame the numbers in context. Approximately 80% of breast cancers are ER-positive, according to the Breast Cancer Research Foundation, meaning ER-negative disease — while more aggressive — is less common. The 67% and 93% figures represent relative differences between exposure groups, not any individual woman's absolute chance of developing breast cancer. Speaking to Healio, White said that on an absolute scale, 'the risk contributed here is going to be lower.'

To strengthen the findings, the researchers also conducted a meta-analysis of seven prior studies in which blood PFAS measurements had been taken before cancer diagnosis. That analysis showed consistent positive associations between ER-negative breast cancer and higher levels of both PFOA and PFOS, according to Healio.

ER-negative tumors do not use estrogen to grow, which means they do not respond to standard hormone-blocking treatments such as tamoxifen or aromatase inhibitors. The fact that the PFAS associations were confined to this hormone-receptor-negative subtype may itself be a clue about how the chemicals act. According to researchers, PFAS may drive cancer risk through nonhormonal biological routes — including alterations in immune function or gene activity — rather than by acting as estrogen mimics.

We did not study mechanisms as part of this paper, and that is an important next step. But our hypothesis would be that other potential mechanisms— Alexandra White, PhD, MSPH, NIH Stadtman Investigator

Medical oncologist Dr. Tiffany Troso-Sandoval, a New York City-based breast and gynecological cancer specialist, told Fox News Digital that PFAS can accumulate in the body and potentially trigger cancerous changes in cells. In her view, the chemicals could impair DNA or undermine the body's capacity to fix that damage or eliminate cancerous cells — though she emphasized that the study demonstrates association rather than proof of causation.

What was interesting about this study is that the link was found only in ER-negative breast cancers, which is a known aggressive subtype of cancer.— Dr. Tiffany Troso-Sandoval, medical oncologist

PFAS are found in nonstick cookware, stain-resistant fabrics, food packaging, firefighting foam, and personal care products. They are called 'forever chemicals' because their chemical bonds break down extremely slowly, allowing them to accumulate in the environment and in human tissue over time. The study drew its data from the Sister Study, a large U.S. research project that brought in more than 50,000 women aged 35 to 74 in the U.S. and Puerto Rico — none of whom had breast cancer at enrollment, but all of whom had a sister previously diagnosed with the disease.

One limitation the researchers acknowledged: the study focused primarily on older PFAS compounds — PFOA and PFOS — that have been largely phased out of production in the United States. Shorter-chain PFAS chemicals are now replacing them, and far less is known about their health effects.

They tend to be shorter-chain compounds and may be less persistent in our bodies and the environment, but we know little about how they may influence health outcomes, such as breast cancer.— Alexandra White, PhD, study leader

First author Che-Jung Chang, PhD, a former NIH research fellow, noted that while PFAS are persistent, exposure is 'potentially modifiable,' and that the findings 'could open new avenues for prevention,' according to Fox News Digital. Troso-Sandoval advised people to review frequently used products and consider switching to stainless steel cookware, avoiding heating food in plastic containers, and checking cosmetics and personal care products for PFAS.

HHS Secretary Robert F. Kennedy Jr., according to Fox News Digital, declared that 'women deserve clear answers about how chemicals in their environment may affect their health' and urged that further investigation be conducted.

Why it matters — PFAS are present in countless everyday products and nearly all human bodies, and this study identifies one of the few known modifiable risk factors for ER-negative breast cancer — a subtype that resists standard hormone therapies and has historically had few prevention targets.

Reported by foxnews.com, hhs.gov, healio.com