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A prospective case-cohort study found that women with higher measured levels of PFOA and PFOS had higher rates of estrogen receptor-negative breast cancer than women with lower levels. A seven-study meta-analysis supported an association for PFOA, but the findings do not establish that PFAS exposure causes cancer.
A prospective study found that higher prediagnosis blood levels of two widely used PFAS chemicals were associated with a higher risk of estrogen receptor-negative breast cancer, a subtype that is generally more aggressive. The results, reported by researchers led by Alexandra J. White of the National Institute of Environmental Health Sciences, show an association rather than proof that the chemicals cause cancer.
In the study, women in the highest exposure group for perfluoro-n-octanoic acid (PFOA) had a higher rate of ER-negative breast cancer than women in the lowest group: the hazard ratio was 1.67, with a 95% confidence interval of 1.10 to 2.53. For perfluorooctane-1-sulfonic acid (PFOS), the corresponding hazard ratio was 1.93 (95% CI 1.15 to 3.22). These comparisons describe relative rates between exposure groups, not an individual woman’s chance of developing cancer.
The research team also pooled results from seven studies. That meta-analysis found an association between PFOA and breast cancer (relative risk 1.30, 95% CI 1.05 to 1.62). The estimate for PFOS was smaller and less certain: relative risk 1.20, with a confidence interval of 0.91 to 1.58, which includes no association.
The main study used data from the Sister Study, a U.S. and Puerto Rico cohort of 50,884 women aged 35 to 74 who had a sister diagnosed with breast cancer. Researchers analyzed 1,609 women who developed breast cancer and a comparison sample of 2,269 women, measuring 17 PFAS in plasma collected before diagnosis. The report appeared in the Journal of Clinical Oncology.
Why ER-Negative Tumors Matter
The findings add to research on possible environmental contributors to ER-negative breast cancer, for which established risk factors are limited compared with some other breast cancer subtypes, the researchers said. ER-negative tumors lack estrogen receptors and are generally more aggressive, making potential risk factors an area of public health interest.
White and colleagues said positive results were generally concentrated among hormone receptor-negative tumors. They proposed that non-hormonal pathways, including possible epigenetic changes or immune effects, could be relevant. Those mechanisms remain explanations under consideration, not conclusions demonstrated by this study.
The results may also matter for chemical oversight. PFOA and PFOS have been phased out of industrial use in many settings and largely replaced by other PFAS, according to the report. The authors said studying the health effects of replacement compounds is a public health priority; the current findings do not establish that those newer substances carry the same risks.
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How Researchers Measured Exposure
The Sister Study enrolled participants between 2003 and 2009. All were free of breast cancer at enrollment and had a full or half-sister with the disease. Blood samples collected before diagnosis allowed the team to assess measured PFAS levels before the cancer outcomes included in the analysis.
The researchers followed the groups for different periods: a median of 5.9 years among women who developed breast cancer and 9.7 years in the comparison sample. They oversampled women with ER-negative tumors, White told MedPage Today, to improve statistical power for a subtype that is diagnosed less often and can be harder to study. Prior analyses, including work using the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial and a French study, had also reported positive associations between PFOA or PFOS and ER-negative tumors.
Not every chemical showed the same pattern. N-methylperfluoro-1-octanesulfonamidoacetic acid had a possible association with ER-negative cancer, but its confidence interval included no association. Perfluoro-n-tridecanoic acid was inversely associated with ER-negative tumors. PFOSA, detected in 6.9% of participants, was associated with ER-positive tumors. For overall breast cancer incidence, most measured PFAS had negligible associations, while several estimates were described as suggestive rather than conclusive.
“Our findings suggest these chemicals may be one contributor to ER-negative breast cancer risk specifically.”
— Alexandra J. White, speaking to MedPage Today
What the Study Cannot Establish
The results show statistical associations, not that exposure to PFOA or PFOS caused an individual’s cancer. Observational studies can identify patterns but cannot, by themselves, rule out other factors that may contribute to the association. The study also involved women with a family history of breast cancer, so its findings may not apply in the same way to every population.
The meta-analysis gives stronger support to an association for PFOA than for PFOS: the PFOS confidence interval included no association. The study also examined many PFAS and tumor outcomes, and results varied by chemical and cancer subtype. The authors’ proposed biological pathways remain hypotheses. It is not clear from these findings how much any person’s exposure changes their absolute risk, or whether exposure reduction changes that risk.
Although White said reducing exposure from sources such as contaminated water would be a reasonable step for people concerned about PFAS, the report does not test whether such steps prevent breast cancer. It also does not determine the effects of replacement PFAS now more widely used.
Research on Replacement PFAS
Further research will be needed to test whether the associations hold in other populations and to clarify how PFAS exposure relates to different breast cancer subtypes. The researchers also pointed to the need to study replacement PFAS, which were not the main focus of these findings but are used more widely after older compounds were phased out.
For now, the report adds evidence to an ongoing research question rather than changing what is known about the cause of breast cancer. People concerned about possible exposure can seek information about local sources, including drinking-water contamination, but the study does not establish a personal risk estimate or a cancer-prevention benefit from any specific action.
Key Questions
What did the study find?
Women in the highest exposure groups for PFOA and PFOS had higher rates of ER-negative breast cancer than women in the lowest groups. The study found an association, not proof that either chemical caused cancer.
What is ER-negative breast cancer?
It is breast cancer in which tumor cells do not have estrogen receptors. The researchers describe ER-negative tumors as generally more aggressive; this study examined associations with PFAS, not treatment or diagnosis.
Does the research show PFAS cause breast cancer?
No. The study was observational and reports associations. It cannot establish that PFAS exposure caused the cancers or determine an individual’s absolute risk.
Did the results apply to all PFAS chemicals?
No. The researchers measured 17 PFAS, and findings differed by chemical and tumor subtype. The report calls for more research on replacement PFAS; it does not show that all PFAS have the same effects.
What happens next in this research?
Researchers need additional studies to test the findings in other populations, clarify possible biological pathways and examine newer PFAS compounds that have replaced PFOA and PFOS in many uses.
Source: medpagetoday.com
