TL;DR
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A prospective case-cohort study found that higher measured levels of PFOA and PFOS were associated with greater risk of estrogen receptor-negative breast cancer. A review of seven studies also supported an association for PFOA, but the findings do not establish that PFAS cause cancer, and researchers say more work is needed, particularly on replacement chemicals.
A prospective study found that women with the highest measured levels of two PFAS chemicals, PFOA and PFOS, had higher rates of estrogen receptor-negative breast cancer than women with the lowest levels. The research, led by Alexandra J. White of the National Institute of Environmental Health Sciences, reports an association—not proof that exposure caused cancer—and a meta-analysis of seven studies supported the PFOA finding more clearly than the PFOS finding.
In the case-cohort analysis, the highest exposure quartile for PFOA was associated with a 67% higher relative risk of ER-negative breast cancer than the lowest quartile (hazard ratio 1.67; 95% confidence interval 1.10–2.53). For PFOS, the corresponding hazard ratio was 1.93 (95% CI 1.15–3.22). These estimates compare exposure groups in the study; they do not give an individual’s absolute chance of developing cancer.
The researchers also pooled findings from seven studies. That analysis found a relative risk of 1.30 for PFOA (95% CI 1.05–1.62). For PFOS, the estimate was 1.20, but its confidence interval included no association (95% CI 0.91–1.58). The findings were reported in the Journal of Clinical Oncology.
The main study used the U.S. and Puerto Rico Sister Study, which enrolled 50,884 women ages 35 to 74 who had a sister diagnosed with breast cancer. Researchers analyzed prediagnostic plasma from 1,609 women who developed breast cancer and a comparison sample of 2,269 women, measuring 17 PFAS. The team oversampled ER-negative cases, which are less common, to improve the analysis’s statistical power. Follow-up had a median of 5.9 years for cases and 9.7 years for the comparison group.
Why ER-Negative Tumors Matter
The findings identify a possible association between PFAS exposure and ER-negative breast cancer, a tumor group researchers described as generally more aggressive and for which established risk factors are limited. The study does not show that PFAS exposure explains an individual cancer diagnosis or quantify the risk for any one person.
White and colleagues wrote that the results were concentrated among hormone receptor-negative tumors. They suggested that possible explanations could include epigenetic changes or immunosuppression, but the study did not establish a mechanism. The findings may inform further research into exposure sources, cancer subtypes and the effects of newer PFAS compounds.
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How Researchers Measured Exposure
PFAS are a broad group of chemicals used in various industrial and consumer applications. PFOA and PFOS, the compounds central to the reported association, have been phased out of industry and largely replaced by other PFAS, according to the source report. The researchers noted that measurable levels of the older compounds remain in many people’s bodies, making it possible to study their health associations even after phaseouts.
The study measured chemicals in blood collected before breast cancer diagnosis, strengthening the timing of the exposure assessment compared with studies that measure levels only after diagnosis. Still, an observational study cannot by itself rule out other factors that may contribute to the association. Earlier studies, including analyses in the U.S. 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 all results pointed in the same direction or met conventional statistical thresholds. The researchers observed a possible association between another PFAS, N-methylperfluoro-1-octanesulfonamidoacetic acid, and ER-negative tumors, but it was not statistically significant. Perfluoro-n-tridecanoic acid was inversely associated with those tumors, while PFOSA was associated with ER-positive tumors. For overall breast cancer incidence, most measured PFAS showed negligible associations.
“Our findings suggest these chemicals may be one contributor to ER-negative breast cancer risk specifically.”
— Alexandra J. White, speaking to MedPage Today
Limits of the Cancer Risk Evidence
The study establishes an association, not causation. It cannot show that PFOA or PFOS directly caused the cancers, determine which exposure sources mattered, or rule out all other explanations. The cohort was made up of women with a sister who had breast cancer, so the participants may not represent all women. Researchers also deliberately oversampled ER-negative cases, and the reported comparisons should not be read as population-wide absolute risks.
The meta-analysis adds evidence for PFOA, but its PFOS estimate was uncertain because the confidence interval included no association. The study also produced mixed results across other compounds and tumor types. It remains unclear whether the associations reflect these specific chemicals, correlated exposures, other factors, or a biological process that can be confirmed in further research.
Research on Newer PFAS
White said future public-health research should include replacement PFAS now more widely used, since the compounds assessed in this study have been phased out but remain detectable in people. Further studies could assess whether the reported associations appear in other populations, investigate possible mechanisms and examine individual tumor subtypes with enough cases for reliable comparisons.
White told MedPage Today that reducing exposure from sources such as contaminated water would be reasonable for people concerned about PFAS. The study does not establish a personal exposure threshold or show that reducing exposure prevents breast cancer. No additional results or follow-up study timetable were specified in the source report.
Key Questions
Did the study prove that PFAS cause breast cancer?
No. It found associations between measured PFOA and PFOS levels and ER-negative breast cancer. Because the research was observational, it cannot establish that the chemicals caused the cancers.
Which chemicals were associated with ER-negative tumors?
The highest exposure groups for PFOA and PFOS had higher estimated risks than the lowest groups in the case-cohort study. The seven-study meta-analysis supported the PFOA association; its PFOS estimate was less certain.
What is ER-negative breast cancer?
It refers to breast tumors that test negative for estrogen receptors. The researchers said these tumors are generally more aggressive and have fewer established risk factors than some other breast cancer groups.
Does this research show how much risk an individual faces?
No. The reported hazard ratios compare study exposure groups and do not provide an individual’s absolute risk. The research also cannot determine whether a particular person’s exposure contributed to a diagnosis.
What should people know about exposure now?
The source report says PFOA and PFOS have been phased out from industry and largely replaced, though measurable levels remain in many people. White said reducing exposure from sources such as contaminated water would be reasonable for those concerned; the study did not test whether doing so prevents cancer.
Source: medpagetoday.com
