California Breast Cancer Research Program

Water is an increasingly precious resource in California as years of drought, climate change, pollution, as well as an expanding population have all stressed the state's drinking water supplies. Currently, there are increasing concerns about whether regulated and unregulated contaminants in drinking water are linked to a variety of human-health outcomes particularly in socially disadvantaged communities with a history of health risks. To begin to address this data gap by broadly assessing contaminant mixture exposures, the current study was designed to collect tapwater samples from communities in Gold Country, the San Francisco Bay Area, two regions of the Central Valley (Merced/Fresno and Kern counties), and southeast Los Angeles for 251 organic chemicals and 32 inorganic constituents. Sampling prioritized low-income areas with suspected water quality challenges and elevated breast cancer rates. Results indicated that mixtures of regulated and unregulated contaminants were observed frequently in tapwater throughout the areas studied and the types and concentrations of detected contaminants varied by region, drinking-water source, and size of the public water system. Multiple exceedances of enforceable maximum contaminant level(s) (MCL), non-enforceable MCL goal(s) (MCLG), and other health advisories combined with frequent exceedances of benchmark-based hazard indices were also observed in samples collected in all five of the study regions. Given the current focus on improving water quality in socially disadvantaged communities, our study highlights the importance of assessing mixed-contaminant exposures in drinking water at the point of consumption to adequately address human-health concerns (e.g., breast cancer risk). Data from this pilot study provide a foundation for future studies across a greater number of communities in California to assess potential linkages between breast cancer rates and tapwater contaminants.

Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals of increasing concern to human health. PFAS contamination in water systems has been linked to a variety of sources including hydrocarbon fire suppression activities, industrial and military land uses, agricultural applications of biosolids, and consumer products. To assess PFAS in California tap water, we collected 60 water samples from inside homes in four different geographic regions, both urban and rural. We selected mostly small water systems with known history of industrial chemical or pesticide contamination and that served socioeconomically disadvantaged communities. Thirty percent of the tap water samples (18) had a detection of at least one of the 32 targeted PFAS and most detections (89 %) occurred in heavily industrialized Southeast Los Angeles (SELA). The residents of SELA are predominately Latino and low-income. Concentrations of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) ranged from 6.8 to 13.6 ng/L and 9.4-17.8 ng/L, respectively in SELA and were higher than State (PFOA: 0.007 ng/L; PFOS: 1.0 ng/L) and national health-based goals (zero). To look for geographic patterns, we mapped potential sources of PFAS contamination, such as chrome plating facilities, airports, landfills, and refineries, located near the SELA water systems; consistent with the multiple potential sources in the area, no clear spatial associations were observed. The results indicate the importance of systematic testing of PFAS in tap water, continued development of PFAS regulatory standards and advisories for a greater number of compounds, improved drinking-water treatments to mitigate potential health threats to communities, especially in socioeconomically disadvantaged and industrialized areas.

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To fill a research gap on firefighter exposures and breast cancer risk, and guide exposure reduction, we aimed to identify firefighter occupational exposures linked to breast cancer. We conducted a systematic search and review to identify firefighter chemical exposures and then identified the subset that was associated with breast cancer. To do this, we compared the firefighter exposures with chemicals that have been shown to increase breast cancer risk in epidemiological studies or increase mammary gland tumors in experimental toxicology studies. For each exposure, we assigned a strength of evidence for the association with firefighter occupation and for the association with breast cancer risk. We identified twelve chemicals or chemical groups that were both linked to breast cancer and were firefighter occupational exposures, including polycyclic aromatic hydrocarbons, volatile aromatics, per- and polyfluoroalkyl substances, persistent organohalogens, and halogenated organophosphate flame retardants. Many of these were found at elevated levels in firefighting environments and were statistically significantly higher in firefighters after firefighting or when compared to the general population. Common exposure sources included combustion byproducts, diesel fuel and exhaust, firefighting foams, and flame retardants. Our findings highlight breast-cancer-related chemical exposures in the firefighting profession to guide equitable worker's compensation policies and exposure reduction.

Recent studies have implemented a calculated additive toxicity (CAT) approach that sums measured disinfection byproduct (DBP) concentrations weighted by their respective in vitro bioassay potencies to estimate their associated risk in disinfected waters. In this study, the CAT approach was used to systematically investigate 21 regulated and unregulated DBPs measured in drinking water at the household level. Water samples from the tap were collected from over 120 randomly selected participants supplied by eight public water systems using four distinct source water types, two types of disinfection processes, and across two seasons. The purpose of this study was to compare CAT using multiple biological end points, examine household variability, identify DBPs driving toxicity, and assess if current regulated DBPs are adequate predictors of unregulated DBPs. Our results support the significance of unregulated DBPs, particularly haloacetonitriles and iodoacetic acid, as drivers of toxicity. Simple linear models between regulated versus unregulated concentrations and CAT were overall weak with 67% considered poor (r ² < 0.3). These results reveal that current regulatory monitoring approaches may not be adequately capturing true household exposure due to higher contribution of unregulated DBPs to CAT and poor predictability between regulated and unregulated DBP-mediated CAT.

Several studies have reported immune modulation by organophosphate (OP) pesticides, but the relationship between OP exposure and SARS-CoV-2 infection is yet to be studied. We used two different measures of OP pesticide exposure (urinary biomarkers (N = 154) and residential proximity to OP applications (N = 292)) to examine the association of early-childhood and lifetime exposure to OPs and risk of infection of SARS-CoV-2 using antibody data. Our study population consisted of young adults (ages 18-21 years) from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Study, a longitudinal cohort of families from a California agricultural region. Urinary biomarkers reflected exposure from in utero to age 5 years. Residential proximity reflected exposures between in utero and age 16 years. SARS-CoV-2 antibodies in blood samples collected between June 2022 and January 2023 were detected via two enzyme linked immunosorbent assays, each designed to bind to different SARS-CoV-2 antigens. We performed logistic regression for each measure of pesticide exposure, adjusting for covariates from demographic data and self-reported questionnaire data. We found increased odds of SARS-CoV-2 infection among participants with higher urinary biomarkers of OPs in utero (OR = 1.94, 95% CI: 0.71, 5,58) and from age 0-5 (OR = 1.90, 95% CI: 0.54, 6.95).

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Enzymatic biocatalysis typically generates less waste, uses less water, and minimizes energy consumption compared to traditional chemical methods. Efficient, cell-free biosynthesis relies on the reuse of its valuable biocatalysts. Immobilization of enzymes on solid supports, such as enzyme carrier resins (ECRs), offers a reliable and widely deployed approach to maximize enzyme turnover in cell-free biosynthesis. We focus on two major bottlenecks associated with optimizing cell-free biocatalysis. First, we apply our lab's 3D-printed labware to screen ECRs in 96-well mini-reactors to optimize enzyme immobilization conditions. Second, we introduce inline infrared spectroscopy to monitor bioreactor output and maximize enzyme productivity. Urease provides a model system for examining immobilization conditions and continuous assessment of biocatalyst performance. As required for the high substrate concentrations to improve process efficiency and minimize waste, urease was studied in unusually high concentrations of its substrate – molar concentrations of urea. The optimized reactor processed 3.24 L of 4.00 M urea at an average volumetric productivity of 13 g ⋅ L−1 ⋅ h−1 over 18 h and achieved an estimated productivity number of >17.4 kg urea processed per g of immobilized urease Type-IX. This workflow can be generalized to most biocatalytic processes and could accelerate adoption of cell-free biosynthesis for greater chemical sustainability.

The disproportionate use of chemical straighteners and skin lighteners by women of color is a growing public health concern given the link between product use and adverse health effects. Prior studies examined product use as an individual choice but neglected social-structural factors, which influence beauty perceptions and personal decisions around product use. We used a community-based participatory research approach to characterize product use by demographics and investigated how racialized beauty norms impact use among 297 women and femme-identifying individuals in Northern Manhattan and the South Bronx. Product use varied by race/ethnicity, nativity, and messaging from family and peers. Black respondents were more likely to ever use chemical straighteners than non-Black respondents (OR = 2.0; 95% CI = 1.2-3.2), as were respondents who heard that family members express a preference for straight hair compared with respondents whose family members expressed mixed preferences about hairstyles (OR = 2.0; 95% CI = 1.1-3.7). Compared with non-Asian respondents and respondents born in the United States, Asian respondents and respondents born in other countries, respectively, had threefold higher odds of ever using skin lighteners (Asian: OR = 3.2; 95% CI = 1.4-7.0; born in other countries: OR = 3.4; 95% CI = 1.9-6.1). Respondents' perceptions that others believe straight hair or lighter skin confer benefits such as beauty, professionalism, or youth were associated with greater use of chemical straighteners and skin lighteners. These findings highlight the pervasiveness of racialized beauty norms and point to the need to reduce the demand for and sale of these products through community education, market-based strategies, and public policy.

Although robustly expressed in the disease-free (DF) breast stroma, CD36 is consistently absent from the stroma surrounding invasive breast cancers (IBCs). In this study, we primarily observed CD36 expression in adipocytes and intralobular capillaries within the DF breast. Larger vessels concentrated in interlobular regions lacked CD36 and were instead marked by the expression of CD31. When evaluated in perilesional capillaries surrounding ductal carcinoma in situ, a nonobligate IBC precursor, CD36 loss was more commonly observed in lesions associated with subsequent IBC. Peroxisome proliferator-activated receptor γ (PPARγ) governs the expression of CD36 and genes involved in differentiation, metabolism, angiogenesis, and inflammation. Coincident with CD36 loss, we observed a dramatic suppression of PPARγ and its target genes in capillary endothelial cells (ECs) and pericytes, which typically surround and support the stability of the capillary endothelium. Factors present in conditioned media from malignant cells repressed PPARγ and its target genes not only in cultured ECs and pericytes but also in adipocytes, which require PPARγ for proper differentiation. In addition, we identified a role for PPARγ in opposing the transition of pericytes toward a tumor-supportive myofibroblast phenotype. In mouse xenograft models, early intervention with rosiglitazone, a PPARγ agonist, demonstrated significant antitumor effects; however, following the development of a palpable tumor, the antitumor effects of rosiglitazone were negated by the repression of PPARγ in the mouse stroma. In summary, PPARγ activity in healthy tissues places several stromal cell types in an antitumorigenic state, directly inhibiting EC proliferation, maintaining adipocyte differentiation, and suppressing the transition of pericytes into tumor-supportive myofibroblasts.