Two 'Forever Chemicals' Linked to Higher Risk of Aggressive ER-Negative Breast Cancer

Years before any of them received a diagnosis, the women in this study gave blood. That stored plasma is now the foundation of a new analysis from the National Institutes of Health, which found that women with higher levels of two widely used industrial chemicals were more likely to develop a particularly aggressive form of breast cancer.

The chemicals are perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), two members of the large family known as PFAS, or per- and polyfluoroalkyl substances. They are used in common consumer products and are nicknamed "forever chemicals" because they do not break down easily in the environment and can stay in the human body for years. The findings appear in the Journal of Clinical Oncology.

The cancer in question is estrogen receptor-negative, or ER-negative, breast cancer. Its tumors lack the receptors that let estrogen help cancer cells grow. Compared with breast cancers that respond to estrogen, ER-negative cancers tend to be more aggressive and carry worse outcomes. Scientists also know comparatively little about what raises the risk of developing them.

The data came from the Sister Study, led by NIH's National Institute of Environmental Health Sciences. Between 2003 and 2009 it enrolled 50,884 women ages 35 to 74 in the United States and Puerto Rico. None had breast cancer at enrollment, but each had a full or half-sister who had been diagnosed. For the PFAS analysis, researchers drew on 1,609 women who went on to develop breast cancer and a comparison sample of 2,269 women. They measured 17 PFAS in blood collected years before diagnosis.

The differences were notable. Women in the highest PFOA group had a 67% higher rate of ER-negative breast cancer than those in the lowest group. For PFOS, the rate was 93% higher, close to double. These are relative differences between groups, not a measure of any individual woman's chance of developing the disease. And there was no clear association between either chemical and breast cancer risk overall; the signal appeared specifically for ER-negative tumors.

"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," said Alexandra White, PhD, an NIH Stadtman Investigator who led the study. First author Che-Jung Chang, PhD, a former NIH research fellow now at the research organization DLH, said that exposure to PFAS is still potentially modifiable, so people can take steps to reduce it, and that the findings could open new avenues for prevention.

HHS Secretary Robert F. Kennedy, Jr. said the study "demands further investigation," and that the administration would pursue the evidence and give women information to protect their health.

Because the strongest links involved tumors without hormone receptors, the authors suggest PFAS may act through non-hormonal biological pathways, such as changes in gene activity or the immune system. The study did not test those explanations. The authors say future work should look at people with higher PFAS exposure and at groups more affected by ER-negative breast cancer.

There is also a question of timing. Most people have measurable PFOA and PFOS in their bodies, but these compounds have largely been phased out and replaced by newer PFAS. "More research is needed," White said, particularly on breast cancer risk tied to those replacement chemicals. The work was supported by NIEHS grants.