NIH Study Links Two Forever Chemicals to Higher Risk of Aggressive ER-Negative Breast Cancer

NIH Study Links Two Forever Chemicals to Higher Risk of Aggressive ER-Negative Breast Cancer

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“Women deserve clear answers about how chemicals in their environment may affect their health,” HHS Secretary Robert F. Kennedy, Jr. said regarding new research connecting environmental contaminants to cancer risks, Oncology Central reported.

A new study by the National Institutes of Health (NIH) has found that women with higher blood levels of two common per- and polyfluoroalkyl substances, known as PFAS, face a higher incidence of estrogen receptor-negative (ER-negative) breast cancer. These substances, often called “forever chemicals” because they do not easily break down, were measured in blood plasma levels prior to cancer diagnoses.

The findings, published in the Journal of Clinical Oncology, specifically highlight the risks associated with two legacy chemicals: perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS).

What Did the Recent NIH Analysis Reveal About the Link Between Forever Chemicals and Aggressive Brea

Aggressive tumor types face higher risk

ER-negative breast cancers are particularly concerning to the medical community because they lack the receptors that allow estrogen to assist in cell growth. According to data from the National Cancer Institute, these tumors tend to be more aggressive and generally result in worse outcomes than hormone-responsive cancers.

The NIH study utilized data from the Sister Study, a long-term research project led by the National Institute of Environmental Health Sciences (NIEHS) that followed 50,884 women in the United States and Puerto Rico. Researchers analyzed 1,609 women who developed breast cancer and compared them to a sample of 2,269 women without the disease.

The statistical differences between the highest and lowest exposure groups were stark. The research showed that women in the highest exposure quartiles experienced significantly higher relative hazards for the ER-negative subtype:

Chemical Compound Increased Risk of ER-Negative Breast Cancer
PFOA (Perfluorooctanoic acid) 67% higher rate
PFOS (Perfluorooctanesulfonic acid) 93% higher rate

While these figures represent relative differences between groups rather than an individual’s absolute probability of diagnosis, they point to a significant correlation. The ASCO Post noted that PFAS concentrations were generally higher among participants who were older, postmenopausal at the time of enrollment, or born before 1945.

The search for biological pathways

Because the strongest associations were found in tumors that do not rely on hormone receptors, scientists are looking beyond traditional hormonal disruption to explain the link. Alexandra White, Ph.D., an NIH Stadtman Investigator who led the study, suggested that the chemicals might influence cancer risk through non-hormonal biological pathways, such as changes in immune system function or gene activity.

“Our findings, which we confirmed using a meta-analysis of prior research, indicate that certain legacy PFAS, including PFOA and PFOS, are associated with a higher risk of ER-negative breast cancer, a more aggressive tumor type with few known risk factors,” explained Dr. White.

The study did not explicitly test these specific biological mechanisms, leaving them as subjects for future investigation. The Independent reported that while PFOA and PFOS are no longer manufactured in the United States, they remain among the most widely used manmade “forever chemicals” in the country. Environmental Protection Agency data has shown that hundreds of public water systems have recorded these chemicals in recent years.

NIH Study Links Two Forever Chemicals to Higher Risk of Aggressive ER-Negative Breast Cancer
Photo: The Independent

There is a complex tension between environmental regulation and industrial transition. While these specific “legacy” compounds have been largely phased out, they have been replaced by newer PFAS variants. Dr. White emphasized that more research is required to evaluate whether these newer replacement chemicals carry similar risks.

Steps for exposure reduction

Despite the persistence of these chemicals in the environment, researchers suggest that exposure may still be modifiable. Che-Jung Chang, Ph.D., a researcher at DLH and the study’s first author, noted that these findings could potentially open new avenues for cancer prevention.

According to reporting by The Independent, individuals looking to mitigate risk can consult with doctors regarding blood tests or utilize water filters that are National Sanitation Foundation-certified to target PFAS. The Environmental Protection Agency also provides resources for understanding and reducing chemical exposure.

The research team indicated that future studies should focus on populations with higher PFAS exposure and those groups more susceptible to ER-negative breast cancer to further clarify these environmental links.

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