Reeves Katherine W, Oulhote Youssef, Grandjean Philippe, Nielsen Flemming
Department of Biostatistics & Epidemiology, University of Massachusetts Amherst, Amherst, MA, USA.
Department of Environmental Medicine and Public Health, Mt. Sinai Icahn School of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA.
Breast Cancer Res. 2025 Aug 18;27(1):148. doi: 10.1186/s13058-025-02103-9.
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 may be 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 cancer-free 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 made by a trained pathologist examining H&E stained section of a core biopsy sample of tissue from the outer upper quadrant of a single breast. 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.
TDLUs were observed in breast tissue samples of 40.3% (N = 106) of the study population, with similar PFAS concentrations between participants with and without 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 (β = 0.03 95% CI -2.75, 2.81; p = 0.98). 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.
全氟和多氟烷基物质（PFAS）可能具有致癌性，动物研究表明其对乳腺发育有有害影响。终末导管小叶单位（TDLU）是分娩后产生乳汁的结构，TDLU的退化通常随年龄增长而发生。大多数乳腺癌起源于TDLU，TDLU退化程度越高，患乳腺癌的风险可能越低。我们估计了正常乳腺组织样本中PFAS浓度与TDLU退化之间的关联。
在来自苏珊·科曼乳腺癌防治组织库（KTB）的263名无癌志愿者参与者的子集中，测量了血清中七种PFAS的浓度。这些参与者均为绝经后女性，目前未使用激素疗法，且有经过培训的病理学家对单乳外上象限组织的核心活检样本进行苏木精-伊红（H&E）染色切片检查后得出的TDLU测量数据。采用贝叶斯核机器回归和分位数-G计算方法，估计该人群中PFAS混合物与TDLU退化指标（TDLU的存在、观察到的TDLU数量以及TDLU跨度中位数）之间经协变量调整后的关联，并按生育状况和母乳喂养史进行分层分析。
在40.3%（N = 106）的研究人群乳腺组织样本中观察到了TDLU，有和没有观察到TDLU的参与者之间PFAS浓度相似。未观察到个体PFAS与观察到的TDLU存在之间有强的、具有统计学意义的关联。PFAS混合物的总体效应表明与观察到TDLU的几率呈倒U形关联，尽管这在统计学上不显著（β = 0.03，95%置信区间 -2.75，2.81；p = 0.98）。在经产妇亚组中，分层分析表明，PFAS混合物与曾经母乳喂养的女性中观察到的TDLU呈正相关，但与从未母乳喂养的女性呈略微负相关。
总体而言，我们的分析不支持PFAS对TDLU退化有显著影响，尽管我们注意到这些发现不适用于绝经前女性或正在使用激素疗法的绝经后女性。
