Perfluoroalkyl substances and breast cancer tissue biomarkers

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PROJECT SUMMARY Per- and polyfluoroalkyl substances (PFAS) are possible carcinogens and have demonstrated detrimental effects on the mammary gland in experimental studies. PFAS are widely used in non-stick, water-resistant, and stain-resistant coatings for consumer products. Nearly all U.S. residents have detectable PFAS in their blood, and their environmental persistence and potential for bioaccumulation raises significant concerns about their long-term health effects. Epidemiologic studies offer preliminary evidence that exposure to certain PFAS may be associated with a doubling of breast cancer risk, and laboratory studies also support breast carcinogenesis following PFAS exposure. Exploring morphological features of human breast tissue can provide important insight on breast carcinogenesis and the impacts of specific exposures. No prior studies have directly explored how human breast tissue is affected by PFAS exposure. Terminal ductal lobular unit (TDLU) involution and mammographic density (MD) are features of human breast tissue that are strongly and independently associated with breast cancer risk and likely lie on the causal pathway. Our overall goal is to understand if PFAS contribute to breast cancer development. Toward this goal, we propose a novel investigation to understand if serum concentrations of common PFAS are associated with TDLU involution and MD. We will leverage the unique resources of the Susan G. Komen for the Cure Tissue Bank (KTB) biorepository, which includes ~9,000 samples of breast tissue donated by healthy volunteers along with relevant epidemiologic data (e.g. medical history, reproductive history); a subset of volunteers also provided a blood sample and/or access to mammograms. We will select the 286 postmenopausal KTB donors with available: a) stored serum sample, b) prior TDLU measurements, and c) mammogram. We will measure a panel of common PFAS in serum samples using a validated assay at a highly experienced and reputable laboratory. We will address the following Specific Aims: to assess associations between serum PFAS concentrations and quantitative measures of 1) TDLU involution and 2) MD. We have an excellent opportunity to capitalize on pre-existing data and biospecimens from the KTB for an innovative exploration of PFAS and these breast tissue features, each of which is independently predictive of breast cancer risk. The proposed work will provide insight on physiologic mechanisms and generate critical preliminary data critical for future larger epidemiologic studies of PFAS and breast cancer risk. As PFAS exposure is ubiquitous, even a small association with breast cancer risk would substantially impact public health.