Environment and Breast Cancer: Science Review

Evidence From Humans
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Breast cancer risk after exposure to perfluorinated compounds in Danish women: a case-control study nested in the Danish National Birth Cohort
Bonefeld-Jorgensen, E. C., Long, M., Fredslund, S. O., Bossi, R., Olsen, J. Cancer Causes Control. 2014. 25:11, 1439-48.
Topic area
Environmental pollutant - Consumer product chemicals PFCs
Study design
Funding agency
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
No analyses based on menopausal status, though women in this study were predominantly premenopausal
Number of Controls
Controls: 233
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
The Danish National Birth Cohort (DNBC) includes about 100,000 pregnancies during the period 1996 to 2010. Approximately half of all pregnant women during this time period were invited by their general practitioners to participate in the cohort. Cases were women identified as breast cancer cases in the National Patient Registry from 1996-2010. Non-breast cancer controls were randomly selected from the entire cohort at baseline, with frequency matching by age and parity.
Exposure Investigated
Exposures investigated
Blood concentrations of sixteen perfluoroalkylated substances (PFAS) obtained during early pregnancy, including ten perfluorocarboxylated acids (PFCAs), five perfluoroalkyl-sulfonates (PFSAs) and perfluorooctane-sulfonamide (PFOSA).
Exposure assessment comment
PFAS serum levels were measured during early pregnancy (between the 6th and 14th weeks) capturing a period when mammary gland cells are rapidly differentiating.
Early life exposures considered
Yes, exposure during pregnancy (mean age at blood draw = 30 years old)
Breast cancer outcome investigated
Primary incident breast cancer
Confounders considered
Other breast cancer risk factors, such as family history, age at first birth, and hormone replacement therapy use, that were taken into account in the study.
Age at blood draw, BMI before pregnancy, total number of gravidities, oral contraceptive use, age at menarche, smoking status during pregnancy, alcohol intake, maternal education, and physical activity
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked “Yes.” “No”, if not.
Strength of associations reported
PFOSA (ng/ml), compared to lowest quintile:
Quintile II (0.93-1.70): aRR 1.38 (95% CI 0.75-2.52)
Quintile III (1.70-2.83): aRR 0.91 (95% CI 0.49-1.66)
Quintile IV (2.83-5.75): aRR 1.11 (95% CI 0.60-2.05)
Quintile V (>5.75): aRR 1.89 (95% CI 1.01-3.54)

PFOSA exposure by age, quintile V (>5.75 ng/ml) vs. quintile I (<0.93 ng/ml):
Among women ages Among women ages >40: aRR 1.62 (95% CI 0.61-4.29)

PFHxS (ng/ml), compared to lowest quintile:
Quintile II (0.76-0.92): aRR 0.64 (95% CI 0.34-1.18)
Quintile III (0.92-1.12): aRR 0.70 (95% CI 0.38-1.29)
Quintile IV (1.12-1.35): aRR 0.38 (95% CI 0.20-0.70)
Quintile V (>1.35): aRR 0.61 (95% CI 0.33-1.12)

PFHxS exposure by age, quintile V (>1.35 ng/ml) vs. quintile I (<0.76ng/ml):
Among women ages Among women ages >40: aRR 1.01 (95% CI 0.40-2.54)

sumPFAS (ng/ml), compared to lowest quintile:
Quintile II: (29.54-35.32): aRR 1.24 (95% CI 0.68-2.25)
Quintile III: (35.32-42.17): aRR 1.41 (95% CI 0.76-2.63)
Quintile IV: (42.17-53.11): aRR 0.96 (0.52-1.78)
Quintile V: (>53.11): aRR 0.94 (0.50-1.78)
Results Comments
No significant associations were found for any of the following PFAS exposures (modeled as continuous and as quintiles): PFOS, PFOA, PFNA, sumPFSA, sumPFCA. No association was found for any exposure quintile when stratified by age > or <= 40 for any of the following PFAS exposures (modeled as continuous and as quintiles): : PFOS, PFOA, sumPFSA, sumPFCA, sum PFAS. Protective associations observed for PFHxS, and these were significant for the 2nd, 4th and 5th quintiles among women ≤ 40 years old at diagnosis.
Author address
Department of Public Health, Centre for Arctic Health & Cellular and Molecular Toxicology, Aarhus University, Aarhus, Denmark, ebj@ph.au.dk.
Reviewers Comments
Elevated PFOSA RR for QV vs QI could be due to chance, especially given multiple testing.