Environmental exposures during windows of susceptibility for breast cancer: a framework for prevention research

Abstract

Background The long time from exposure to potentially harmful chemicals until breast cancer occurrence poses challenges for designing etiologic studies and for implementing successful prevention programs. Growing evidence from animal and human studies indicates that distinct time periods of heightened susceptibility to endocrine disruptors exist throughout the life course. The influence of environmental chemicals on breast cancer risk may be greater during several windows of susceptibility (WOS) in a woman’s life, including prenatal development, puberty, pregnancy, and the menopausal transition. These time windows are considered as specific periods of susceptibility for breast cancer because significant structural and functional changes occur in the mammary gland, as well as alterations in the mammary micro-environment and hormone signaling that may influence risk. Breast cancer research focused on these breast cancer WOS will accelerate understanding of disease etiology and prevention. Main text Despite the plausible heightened mechanistic influences of environmental chemicals on breast cancer risk during time periods of change in the mammary gland’s structure and function, most human studies of environmental chemicals are not focused on specific WOS. This article reviews studies conducted over the past few decades that have specifically addressed the effect of environmental chemicals and metals on breast cancer risk during at least one of these WOS. In addition to summarizing the broader evidence-base specific to WOS, we include discussion of the NIH-funded Breast Cancer and the Environment Research Program (BCERP) which included population-based and basic science research focused on specific WOS to evaluate associations between breast cancer risk and particular classes of endocrine-disrupting chemicals—including polycyclic aromatic hydrocarbons, perfluorinated compounds, polybrominated diphenyl ethers, and phenols—and metals. We outline ways in which ongoing transdisciplinary BCERP projects incorporate animal research and human epidemiologic studies in close partnership with community organizations and communication scientists to identify research priorities and effectively translate evidence-based findings to the public and policy makers. Conclusions An integrative model of breast cancer research is needed to determine the impact and mechanisms of action of endocrine disruptors at different WOS. By focusing on environmental chemical exposure during specific WOS, scientists and their community partners may identify when prevention efforts are likely to be most effective.

Environmental Exposures during Puberty: Window of Breast Cancer Risk and Epigenetic Damage

“…During puberty the female breast undergoes rapid changes: proliferating terminal end buds and elongation of the ducts promote the formation of primitive lobular structures and growth of the ductal tree [2,3] ( Figure 1A). These rapid structural and cellular changes are thought to create a "window of susceptibility" ( Figure 1A) [4].…”

“…Epidemiologic studies provide evidence that medications [5] and disease [6,7] before and during puberty, increase subsequent breast cancer risk; studies on breast cancer risk and environmental exposures before and during puberty are both difficult and important. Increasingly, prospective cohorts are being designed to investigate events that occur during this key window of susceptibility [4].…”

“…Epidemiologic and laboratory studies provide evidence that environmental exposures during puberty are associated with an increased adult risk of breast cancer. In experimental studies on rats, exposure to the carcinogen dimethylbenz [a] anthracene (DMBA) during puberty resulted in the highest number of tumors (vs. other times of life) [4]. In transgenic mice, exposure to high estrogens during puberty resulted in mammary hyperplasia and breast cancers [8,9].…”

Serum Levels of Commonly Detected Persistent Organic Pollutants and Per- and Polyfluoroalkyl Substances (PFASs) and Mammographic Density in Postmenopausal Women

“…MD has been associated with established risk factors of breast cancer such as having fewer children, later menopause, and receiving estrogen and progestin combined hormone therapy [26][27][28]. For these reasons, MD has been used as an early marker of breast cancer in clinical trials [29,30] and etiological studies of breast cancer [31][32][33][34][35][36]. A cross-sectional study investigating the associations between breast cancer risk factors and MD can provide useful insights into their roles in breast cancer [31,32].…”

“…For these reasons, MD has been used as an early marker of breast cancer in clinical trials [29,30] and etiological studies of breast cancer [31][32][33][34][35][36]. A cross-sectional study investigating the associations between breast cancer risk factors and MD can provide useful insights into their roles in breast cancer [31,32]. We investigated the association between serum levels of POPs and MD, a strong risk factor for breast cancer, using data from control participants in a breast cancer case-control study nested in the California Teachers Study (CTS) [13].…”