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BACKGROUND: Tumor recurrence and metastatic progression remains the leading cause for breast cancer related mortalities. However, the proteomes of patient- matched primary breast cancer (BC) and metastatic lesions have not yet been identified, due to the lack of clinically annotated longitudinal samples. In this study, we evaluated the global-proteomic landscape of BC patients with and without distant metastasis as well as compared the proteome of distant metastatic disease with its corresponding primary BC, within the same patient. METHODS: We performed mass spectrometry-based proteome profiling of 73 serum samples from 51 BC patients. Among the 51 patients with BC, 29 remained metastasis-free (henceforth called non-progressors), and 22 developed metastases (henceforth called progressors). For the 22 progressors, we obtained two samples: one collected within a year of diagnosis, and the other collected within a year before the diagnosis of metastatic disease. MS data were analyzed using intensity-based absolute quantification and normalized before differential expression analysis. Significantly differentially expressed proteins (DEPs; absolute fold-change ≥ 1.5, P-value < 0.05 and 30% abundance per clinical group) were subjected to pathway analyses. RESULTS: We identified 967 proteins among 73 serum samples from patients with BC. Among these, 39 proteins were altered in serum samples at diagnosis, between progressors and non-progressors. Among these, 4 proteins were further altered when the progressors developed distant metastasis. In addition, within progressors, 20 proteins were altered in serum collected at diagnosis versus at the onset of metastasis. Pathway analysis showed that these proteins encoded pathways that describe metastasis, including epithelial-mesenchymal transition and focal adhesion that are hallmarks of metastatic cascade. CONCLUSIONS: Our results highlight the importance of examining matched samples from distant metastasis with primary BC samples collected at diagnosis to unravel subset of proteins that could be involved in BC progression in serum. This study sets the foundation for additional future investigations that could position these proteins as non-invasive markers for clinically monitoring breast cancer progression in patients.
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Background: Excessive fluoride consumption affects reproductive and child health. We examined the association between levels of fluoride in drinking water and birth weight, in the National Health and Nutrition Examination Survey 2013−2016, after adjusting for known risk factors Low Birth Weight (LBW) including age, smoking, and socio-demographic variables including education, food security, health care access, and health status. Methods: The study included 7147 and 6858 women with complete birth weight and water fluoride data, respectively. Linear regression models evaluated the association between water fluoride and birth weight across racial/ethnic groups. The odds of delivering an LBW infant (<2500 g) compared to an infant weighing ≥ 2500 g, as well as the odds of delivering a Very Low Birth Weight (VLBW, <1500 g) infant compared to an LBW infant were explored in separate logistic regression models. Results: Women with LBW infants were exposed to significantly higher levels of water fluoride compared to those with normal birth weight infants. Our findings suggest a significant association between excess water fluoride exposure (>0.7 ppm) and LBW weight in Hispanic women, independent of established LBW risk factors. In logistic regression models, Hispanic women exposed to increased levels of water fluoride were 1.5 times more likely to give birth to an LBW infant and 3.5 more likely to give birth to a VLBW infant. Conclusion: Taken together, these findings can inform public health education strategies that highlight water fluoride as a potential risk factor during pregnancy in Hispanic women. More research is needed to confirm these findings.