Vicky Chang

Ph.D., M.P.H

Occupational and Environmental Epidemiology Branch, DCEG, NCI

Postdoctoral Fellow

PLCO (Learn more about this study)

2021-0016

Jul 9, 2021

Serum concentrations of per- and polyfluoroalkyl substances and breast cancer risk among postmenopausal women: A nested case-control study in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals used in a wide range of consumer products and industrial applications. Despite decreased production of PFAS in the United States since the early 2000s, these chemicals are highly persistent in the environment and remain ubiquitous contaminants of soil and water. Once absorbed, certain PFAS can accumulate in the human body over long periods of time, and recent data suggest that >98% of the U.S. population have detectable levels of PFAS in their blood.
Emerging evidence has linked PFAS exposure to risk of cancer, particularly kidney and testicular cancers. As endocrine-disrupting chemicals with potential estrogenic properties, PFAS have also been suggested to play a role in breast cancer development. For example, in vitro studies have demonstrated the ability of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA)—two of the most commonly detected PFAS—to promote malignant transformation of human breast cells and enhance growth of estrogen-dependent breast cancer cells. In addition, PFAS exposure has been shown to alter mammary gland development and induce mammary fibroadenoma in rodents. However, despite biological plausibility, epidemiological evidence for the association between PFAS and breast cancer risk remains limited and inconclusive. Two cohort studies conducted among highly exposed geographically-defined populations did not find a statistically significant association between model-estimated PFOA exposure levels and breast cancer risk. Meanwhile, inconsistent results were reported by several case-control studies, most of which had small sample sizes and relied on PFAS measured in blood samples collected after breast cancer diagnosis. Recently, a nested case-control study (194 postmenopausal breast cancer cases and 194 controls) in the French E3N cohort reported an elevated risk of hormone receptor-positive breast cancer associated with higher pre-diagnostic serum PFOS levels, as well as associations of low-to-medium (but not the highest) PFOS and PFOA levels with hormone receptor-negative tumors. These findings provide support for the potential role of PFAS in postmenopausal breast cancer risk and highlight the importance of considering potential differences by hormone receptor status, although further investigation is warranted in larger studies.
In order to achieve sufficient statistical power given the magnitude of previously observed associations, we propose to conduct a nested case-control study of 1,601 breast cancer cases and an equivalent number of individually matched controls in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial to investigate the associations between pre-diagnostic serum concentrations of various PFAS and risk of postmenopausal breast cancer. This will be the largest prospective study to assess directly measured circulating PFAS levels in relation to breast cancer risk, including measurements of a range of PFAS beyond PFOS and PFOA. The large sample size will also allow more detailed evaluation of potential etiologic heterogeneity by hormone receptor subtype, as well as exploration of interactions between PFAS and known breast cancer risk factors, which may provide additional insights into the role of PFAS in breast cancer etiology. The proposed study is expected to make a novel and important contribution to the limited epidemiological literature on PFAS and breast cancer.