AS736 - Serum concentrations of per- and polyfluoroalkyl substances and breast cancer risk among postmenopausal women: A nested case-control study in the Women’s Health Initiative

Investigator Names and Contact Information

Vicky Chang (chidan.chang@nih.gov)

Jonathan Hofmann, Gretchen Gierach

Introduction/Intent

Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals used in various industrial applications and consumer products since the 1940s. Despite the phase-out of certain legacy PFAS, such as perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), in the early 2000s, these compounds are highly persistent in the environment and in the human body and remain detectable in almost the entire U.S. population. As endocrine-disrupting chemicals, PFAS have been suggested to play a role in the development of breast cancer. However, the epidemiologic evidence is inconclusive, with most studies relying on model-estimated exposures or PFAS measurements in blood collected after cancer diagnosis. Recent work by our team and another group suggests that PFAS may be differentially associated with breast cancer subtypes, with positive associations observed between prediagnostic serum PFOS levels and hormone receptor-positive tumors, and possibly between PFOA and hormone receptor-negative tumors; however, these studies had limited statistical power for the subtype-specific analyses and did not measure other PFAS compounds beyond PFOS and PFOA.

We propose to conduct a nested case-control study within the Women’s Health Initiative (Observational Study) to investigate whether prediagnostic serum concentrations of eight commonly detected PFAS are associated with risk of postmenopausal invasive breast cancer, overall and by hormone receptor status, and with risk of ductal carcinoma in situ (DCIS). This study will include 850 invasive breast cancer cases (500 ER+/PR+, 150 ER+/PR–, 200 ER–/PR–) and 850 matched controls, as well as an additional 250 DCIS cases. We will quantify PFAS concentrations in sera (250 µL) collected at baseline from each individual. To our knowledge, this will be the largest prospective study to date to directly assess circulating PFAS levels in relation to breast cancer risk and the first to examine associations between PFAS and DCIS, which may provide new insights into the role of PFAS in breast cancer etiology.

SPECIFIC AIMS

1. To evaluate associations between prediagnostic serum concentrations of PFAS [PFOS, PFOA, perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), 2-N-methyl-perfluorooctane sulfonamido acetic acid (MeFOSAA), and 2-N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA)] and risk of invasive breast cancer;
2. To evaluate associations between prediagnostic serum PFAS concentrations and risk of invasive breast cancer according to hormone receptor [estrogen receptor (ER), progesterone receptor (PR), and joint ER/PR] status; and
3. To evaluate associations between prediagnostic serum PFAS concentrations and risk of DCIS.