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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 meta-analysis supported an association for PFOA, but the results do not show that PFAS caused cancer, and researchers say more work is needed, particularly on replacement chemicals.
A prospective study found that women with higher measured levels of two PFAS chemicals—PFOA and PFOS—had a higher risk of estrogen receptor-negative (ER-negative) breast cancer than women with lower levels, researchers reported in the Journal of Clinical Oncology. The findings show an association, not proof that the chemicals cause cancer, and are notable because ER-negative tumors have fewer established risk factors and are generally more aggressive.
Researchers led by Alexandra J. White of the National Institute of Environmental Health Sciences analyzed prediagnostic blood samples from participants in the U.S. Sister Study. In the study’s highest exposure quartile, PFOA was associated with a higher rate of ER-negative breast cancer than 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% CI 1.15 to 3.22). These estimates compare groups within this study; they do not indicate that most exposed people will develop cancer.
The analysis included 1,609 women who developed breast cancer and a comparison sample of 2,269 women from a cohort of 50,884 breast-cancer-free women, all of whom had a sister diagnosed with breast cancer. Participants were enrolled between 2003 and 2009. The team measured 17 PFAS in plasma collected before diagnosis, and oversampled women with ER-negative tumors to improve the analysis of a less frequently diagnosed subtype.
A meta-analysis of seven studies also found an association between PFOA and breast cancer risk (relative risk 1.30; 95% CI 1.05 to 1.62). The pooled result for PFOS was weaker and its confidence interval included no association (RR 1.20; 95% CI 0.91 to 1.58). Other findings varied: one PFAS was inversely associated with ER-negative tumors, while a potential link for another did not reach statistical significance.
Why ER-Negative Tumors Matter
The results add evidence to research on environmental exposures and ER-negative breast cancer, a subtype for which researchers say established risk factors are limited. White and colleagues wrote that their positive findings were generally concentrated among hormone receptor-negative tumors. That pattern could help guide future studies of whether specific exposures relate differently to different tumor types.
The study does not establish a cause-and-effect relationship or show how much an individual’s risk changes in everyday terms. Still, the findings matter for public health because PFOA and PFOS remain measurable in many people, according to White, even though the compounds assessed have been phased out in industry and largely replaced by other PFAS. Any practical response must account for the distinction between an observed association and a demonstrated health effect.
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What the Sister Study Measured
The Sister Study follows women in the United States and Puerto Rico who had a full or half-sister diagnosed with breast cancer. Its participants were breast-cancer-free when they enrolled, making it possible to measure chemical levels before a later diagnosis. The researchers followed the cancer cases for a median of 5.9 years and the comparison group for a median of 9.7 years, according to the report.
PFAS are a broad group of manufactured chemicals often called “forever chemicals” because many persist in the environment. The report focuses on PFOA and PFOS, not every chemical in the PFAS family. The authors discussed possible nonhormonal pathways, including epigenetic changes and effects on the immune system, but this study did not test those mechanisms directly.
“Our findings suggest these chemicals may be one contributor to ER-negative breast cancer risk specifically.”
— White, speaking to MedPage Today
Limits of the PFAS Findings
The study is observational: it identifies associations between measured PFAS levels and later diagnoses, but cannot establish that exposure caused the cancers. The supplied report does not provide enough detail to determine how factors such as other exposures or differences among participants may have affected the estimates. The results also come from women with a family history of breast cancer, so it is not clear how directly they apply to all women.
Several estimates were uncertain. For PFOS, the meta-analysis confidence interval included no association; another possible association in the main study also failed to reach statistical significance. The authors reported negligible associations between most other PFAS measured and overall breast cancer incidence. The findings should not be interpreted as evidence that every PFAS has the same relationship to breast cancer, or that an individual’s exposure predicts a diagnosis.
Research on Replacement Chemicals
Further studies will be needed to test whether the PFOA and PFOS associations hold in other populations and to clarify why the reported signal was concentrated in hormone receptor-negative tumors. Researchers also need to examine the health effects of replacement PFAS that are now more widely used, a priority White raised in her comments. The report does not specify a planned follow-up study or timetable.
Key Questions
Did the study prove that PFAS cause breast cancer?
No. The researchers found associations between higher measured PFOA and PFOS levels and ER-negative breast cancer, but an observational study cannot establish that the chemicals caused the disease.
Which breast cancer subtype was associated with higher PFOA and PFOS?
The reported associations were concentrated in estrogen receptor-negative breast cancer. The study did not report the same pattern across all breast cancer types.
What did the meta-analysis find?
Across seven studies, the meta-analysis supported an association between PFOA and breast cancer risk. The PFOS estimate was weaker, and its confidence interval included no association.
Should people change their behavior based on these results?
The report does not establish a personal risk level or show that reducing exposure changes cancer risk. White said reducing exposure from sources such as contaminated water would be reasonable for people concerned about PFAS, but the study did not measure the effect of doing so.
What remains to be studied?
Researchers need to test the findings in other populations, investigate possible explanations for the subtype pattern, and study the health effects of PFAS replacement chemicals now used more widely.
Source: medpagetoday.com
