# Associations of Perfluoroalkyl substances (PFAS) with terminal ductal lobular unit involution of the normal breast

## TL;DR

This study investigates whether perfluoroalkyl substances (PFAS) affect TDLU involution in postmenopausal women's breast tissue, finding no strong evidence of an association.

## Contribution

The study provides new insights into the potential effects of PFAS on breast tissue involution in postmenopausal women.

## Key findings

- No strong, statistically significant associations were found between individual PFAS and TDLU presence.
- The PFAS mixture showed an inverted U-shaped association with TDLU presence, though not statistically significant.
- Among parous women, breastfeeding history modified the association between PFAS and TDLU presence.

## Abstract

Per- and polyfluoroalkyl substances (PFAS) may be carcinogenic, and animal studies demonstrate their harmful effects on mammary gland development. Terminal ductal lobular units (TDLUs) are the structures that produce milk following childbirth, and involution of TDLUs normally occurs with aging. Most breast cancers arise from TDLUs, and a greater degree of TDLU involution is associated with lower breast cancer risk. We estimated associations between PFAS concentrations and TDLU involution in normal breast tissue samples.

Concentrations of seven PFAS were measured in serum provided by a subset of 263 healthy volunteer participants from the Susan G. Komen for the Cure Tissue Bank (KTB) who were postmenopausal, not currently using hormone therapy, and had available TDLU measurements. Bayesian kernel machine regression and quantile-G computation were used to estimate covariate-adjusted associations between the PFAS mixture and measures of TDLU involution (presence of TDLUs, number of observed TDLUs, and median TDLU span) within this population and with stratification on parity and breastfeeding history.

Distributions of PFAS were similar between participants with (N = 106) and without (N = 157) observed TDLUs. No strong, statistically significant associations were observed between individual PFAS and presence of observed TDLUs. The overall effect of the PFAS mixture suggested an inverted U-shaped association with odds of observed TDLUs, although this was not statistically significant. Among the subgroup of parous women, stratified analyses suggested a positive association between the PFAS mixture and observed TDLUs among those who had ever breastfed, but a slightly negative association among those who had never breastfed.

Overall, our analysis does not support meaningful effects of PFAS on TDLU involution, although we note that these findings are not applicable to premenopausal women or to postmenopausal women using hormone therapy.