The National Institutes of Health on Thursday reported that women with higher blood levels of two common forever chemicals were more likely to develop estrogen receptor-negative breast cancer. That form of the disease tends to be more aggressive and to have worse outcomes than breast cancers that respond to the hormone estrogen, the agency said. The analysis found no clear association between the two chemicals and breast cancer risk overall.
The chemicals are perfluorooctanoic acid, known as PFOA, and perfluorooctanesulfonic acid, known as PFOS. They are part of a large group called per- and polyfluoroalkyl substances, or PFAS, used in common consumer products. Often called forever chemicals, PFAS do not break down easily in the environment and can remain in the body for years, according to NIH, part of the U.S. Department of Health and Human Services.
Estrogen receptor-negative, or ER-negative, tumors lack receptors that allow estrogen to help cancer cells grow. Scientists know less about what raises the risk of this type of breast cancer, NIH said.
“This NIH study links two forever chemicals to a higher risk of ER-negative breast cancer and demands further investigation,” said HHS Secretary Robert F. Kennedy, Jr.
NIH researchers and their collaborators measured 17 PFAS in blood collected years before the women were diagnosed with cancer. Women in the group with the highest PFOA levels had a 67% higher rate of ER-negative breast cancer than those in the lowest group. For PFOS, the rate was 93% higher, or nearly twice as high. Those numbers describe relative differences between groups, not an individual woman’s chance of getting breast cancer, according to NIH.
The research drew on the Sister Study, led by NIH’s National Institute of Environmental Health Sciences. The larger study enrolled 50,884 women ages 35 to 74 in the United States and Puerto Rico from 2003 to 2009. None had breast cancer when they joined, but each had a full or half-sister who had been previously diagnosed with breast cancer. For the PFAS analysis, researchers included 1,609 women who developed breast cancer and a comparison sample of 2,269 women.
NIH Stadtman Investigator Alexandra White, who led the study, said the findings were confirmed with a meta-analysis of earlier research. The results appear in the Journal of Clinical Oncology. White said certain older 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.
Because the strongest associations involved tumors without hormone receptors, the authors suggest that PFAS may affect cancer risk through other, non-hormonal biologic pathways. Possible pathways include changes in gene activity or the immune system. The study did not test those explanations, NIH said.
First author Che-Jung Chang, a former research fellow at NIH and a current researcher at DLH, a scientific research organization, said the findings matter for women’s health broadly. Chang said exposure is still potentially modifiable, meaning people can take steps to reduce it, and the findings could open new avenues for prevention.
Although most people have measurable levels of PFOA and PFOS in their bodies, the compounds have been largely phased out and replaced with newer PFAS, according to NIH. “More research is needed, particularly evaluating the risk of breast cancer associated with newer replacement PFAS chemicals,” White said. The authors say future studies should evaluate people with higher PFAS exposure and groups more affected by ER-negative breast cancer.