In utero exposure to poly- and perfluoroalkyl substances (PFASs) and subsequent breast cancer.

We tested the hypothesis that maternal perinatal serum levels of poly and perfluoroalkyl substances (PFASs) predict risk for breast cancer in daughters in a 54-year follow-up of 9300 daughters born 1959-1967 in the Child Health and Development Studies pregnancy cohort. Total cholesterol and PFASs were measured in archived maternal perinatal serum for 102 daughter breast cancer cases diagnosed by age 52, and 310 controls matched on birth year and blood draw trimester. High maternal N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA), a precursor of perfluorooctane sulfonic acid (PFOS), in combination with high maternal total cholesterol predicted a 3.6-fold increased risk of breast cancer (pinteraction<0.05). Conversely, maternal PFOS was associated with decreased daughters' breast cancer risk. Predictions were robust to alternative modeling and independent of other maternal factors. Future generations continue to be exposed to ubiquitous, persistent PFASs. These findings are relevant to breast cancer prevention if confirmed experimentally and where possible, in additional epidemiology studies of internal doses of PFASs and other chemical mixtures especially during vulnerable windows in early life.

DDT Exposure in Utero and Breast Cancer.

CONTEXT: Currently no direct evidence links in utero dichlorodiphenyltrichloroethane (DDT) exposure to human breast cancer. However, in utero exposure to another xenoestrogen, diethylstilbestrol, predicts an increased breast cancer risk. If this finding extends to DDT, it could have far-reaching consequences. Many women were heavily exposed in utero during widespread DDT use in the 1960s. They are now reaching the age of heightened breast cancer risk. DDT exposure persists and use continues in Africa and Asia without clear knowledge of the consequences for the next generation. HYPOTHESIS: In utero exposure to DDT is associated with an increased risk of breast cancer. DESIGN: This was a case-control study nested in a prospective 54-year follow-up of 9300 daughters in the Child Health and Development Studies pregnancy cohort (n = 118 breast cancer cases, diagnosed by age 52 y and 354 controls matched on birth year). SETTING AND PARTICIPANTS: Kaiser Foundation Health Plan members who received obstetric care in Alameda County, California, from 1959 to 1967, and their adult daughters participated in the study. MAIN OUTCOME MEASURE: Daughters' breast cancer diagnosed by age 52 years as of 2012 was measured. RESULTS: Maternal o,p'-DDT predicted daughters' breast cancer (odds ratio fourth quartile vs first = 3.7, 95% confidence interval 1.5-9.0). Mothers' lipids, weight, race, age, and breast cancer history did not explain the findings. CONCLUSIONS: This prospective human study links measured DDT exposure in utero to risk of breast cancer. Experimental studies are essential to confirm results and discover causal mechanisms. Findings support classification of DDT as an endocrine disruptor, a predictor of breast cancer, and a marker of high risk.