TL;DR
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A prospective study found that women in its highest exposure groups for PFOA and PFOS had higher rates of estrogen receptor-negative breast cancer than women in the lowest groups. A seven-study meta-analysis supported an association for PFOA, but the research does not establish that these chemicals cause cancer, and results differed by compound and tumor type.
A prospective study linked higher exposure to two PFAS chemicals—PFOA and PFOS—with a higher risk of estrogen receptor-negative breast cancer, a subtype that is generally more aggressive. The findings, published in the Journal of Clinical Oncology, show an association, not proof that exposure caused the cancers.
In the Sister Study analysis, women in the highest exposure quartile for PFOA had a higher risk of ER-negative breast cancer than women in the lowest quartile (hazard ratio 1.67; 95% confidence interval 1.10 to 2.53). For PFOS, the corresponding hazard ratio was 1.93 (95% confidence interval 1.15 to 3.22). These estimates compare exposure groups within the study; they do not give an individual’s absolute chance of developing cancer.
The research team, led by Alexandra J. White of the National Institute of Environmental Health Sciences, analyzed prediagnostic blood plasma and measured 17 PFAS. The study included 1,609 women who developed breast cancer and a comparison sample of 2,269 women from a larger cohort. Participants were followed for median periods of 5.9 and 9.7 years, respectively. The researchers oversampled women with ER-negative tumors because those cancers are less common and harder to study.
A meta-analysis of seven studies also found an association between PFOA and breast cancer risk (relative risk 1.30; 95% confidence interval 1.05 to 1.62). For PFOS, the pooled estimate was 1.20, but its confidence interval crossed the point at which no association would be indicated (0.91 to 1.58). The authors reported that positive findings were generally concentrated in hormone receptor-negative tumors, rather than breast cancer overall.
Why ER-Negative Findings Matter
The results add to research on possible environmental contributors to ER-negative breast cancer, for which the study authors said there are limited established risk factors. This subtype is generally more aggressive, making better understanding of potential risks a public health concern. However, the study cannot show that PFAS exposure caused the tumors or determine how much these chemicals contribute to any person’s risk.
The findings also matter because the compounds studied have been phased out of industrial use and largely replaced by other PFAS, according to the researchers. White told MedPage Today that many people still have measurable levels of the older compounds in their bodies. The results support continued research into both lingering exposure and the health effects of replacement chemicals, rather than a conclusion that the newer compounds have the same effects.
White said that reducing exposure from sources such as contaminated water would be a reasonable step for people concerned about PFAS. That comment is not evidence that an individual action prevents breast cancer; the study did not test exposure-reduction measures or their effects on cancer risk.
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How the Sister Study Tracked Exposure
The Sister Study enrolled 50,884 women ages 35 to 74 in the United States and Puerto Rico from 2003 to 2009. Each participant had a full or half-sister diagnosed with breast cancer, but participants themselves were breast-cancer-free at enrollment. That family history means the cohort is not a random sample of all women, a consideration when interpreting how broadly the results apply.
For this analysis, researchers used blood samples collected before diagnosis to measure PFAS, then compared cancer outcomes across exposure levels. Measuring chemicals before diagnosis helps establish that the recorded exposure preceded the identified cancer, but it does not rule out other factors that could influence the association. The team also examined several other PFAS, with results that varied by chemical and tumor subtype.
For example, a possible link between n-methylperfluoro-1-octanesulfonamidoacetic acid and ER-negative cancer did not reach statistical significance. Perfluoro-n-tridecanoic acid was inversely associated with ER-negative tumors, while PFOSA was associated with ER-positive tumors. For overall breast cancer incidence, most measured PFAS had negligible associations, according to the report.
“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 PFAS Risk Evidence
The study found statistical associations, but it cannot establish cause and effect. Other differences between participants could have contributed to the results, and the reported hazard ratios do not describe absolute risk. The study population also consisted of women with a sister who had breast cancer, so findings may not translate directly to all women.
The pooled PFOS result from the meta-analysis was less conclusive than the PFOA result: its confidence interval included no association. Several findings for other PFAS were also uncertain, including the potential association between one compound and ER-negative cancer, which did not reach statistical significance. The authors reported negligible associations between most PFAS and overall breast cancer incidence.
It is not clear from these findings which biological processes, if any, explain the observed patterns. The authors discussed possible nonhormonal mechanisms, including epigenetic changes and immunosuppression, but the study did not demonstrate that those processes caused the cancers. The risk associated with replacement PFAS also remains untested in this analysis.
Research on Replacement PFAS
The authors called for more attention to the health effects of PFAS now used as replacements for older compounds. Further studies will be needed to test whether the associations hold in other populations, clarify how exposure relates to specific tumor subtypes, and examine possible biological pathways. The supplied report does not identify a planned follow-up study or a timetable for new results.
For readers concerned about exposure, White said that reducing exposure from sources such as contaminated water would be reasonable. The study did not evaluate specific interventions, provide individual risk estimates, or show that lowering exposure changes breast cancer outcomes. Questions about personal exposure or cancer risk should be discussed with a qualified health professional.
Key Questions
Did the study prove that PFAS cause breast cancer?
No. The researchers found associations between higher measured PFOA and PFOS exposure and ER-negative breast cancer. The study design does not establish that either chemical caused the cancers.
Which cancer subtype was linked to PFOA and PFOS?
The strongest findings described in the report concerned estrogen receptor-negative breast cancer. The authors said positive findings were generally concentrated among hormone receptor-negative tumors.
What did the meta-analysis find?
The combined analysis of seven studies supported an association for PFOA (relative risk 1.30; 95% confidence interval 1.05 to 1.62). Its PFOS estimate was less conclusive because the confidence interval included no association.
Do the results show that all PFAS increase breast cancer risk?
No. Results varied by chemical and tumor type. The report said most measured PFAS had negligible associations with overall breast cancer incidence, and some other findings were uncertain or in the opposite direction.
What can people do if they are concerned about PFAS exposure?
White told MedPage Today that reducing exposure from sources such as contaminated water would be reasonable. This study did not test whether doing so lowers cancer risk; people with personal health concerns can seek advice from a qualified health professional.
Source: medpagetoday.com
