Altered Leukocyte Sphingolipid Pathway in Breast Cancer.

Sphingolipid metabolism pathway is essential in membrane homeostasis, and its dysfunction has been associated with favorable tumor microenvironment, disease progression, and chemotherapy resistance. Its major components have key functions on survival and proliferation, with opposing effects. We have profiled the components of the sphingolipid pathway on leukocytes of breast cancer (BC) patients undergoing chemotherapy treatment and without, including the five sphingosine 1-phosphate (S1P) receptors, the major functional genes, and cytokines, in order to better understand the S1P signaling in the immune cells of these patients. To the best of our knowledge, this is the first characterization of the sphingolipid pathway in whole blood of BC patients. Skewed gene profiles favoring high SPHK1 expression toward S1P production during BC development was observed, which was reversed by chemotherapy treatment, and reached similar levels to those found in healthy donors. Such levels were also correlated with high levels of TNF-α. Our data revealed an important role of the sphingolipid pathway in immune cells in BC with skewed signaling of S1P receptors, which favored cancer development even under chemotherapy, and may probably be a trigger of cancer resistance. Thus, these molecules must be considered as a target pathway for combined BC therapeutics.

Physical activity is associated with malignant and benign breast diseases in low-income Brazilian women.

We compared the relationships among percentage of body fat (%BF) and physical activity with breast cancer (BC) and benign breast diseases (BBD) in low-income Brazilian women. A case-control study including 106 incident BC cases, 178 incident BBD cases, and 181 control women recruited from a public hospital-based screening center was conducted. Logistic regression models showed that sedentary women have a higher odds of developing BC in the age adjusted model [odds ratio (OR) = 2.39, 95% confidence interval (CI) 1.43-3.99]. After adjusting for hormonal-related risk factors and family history of breast cancer (OR = 2.94, 95% CI 1.50-5.79) and also for the % BF (OR = 2.71, 95% CI 1.36-5.37) the odds remained high. Independent of the adjustments made, %BF did not affect the odds for developing BC. When the same models were tested for women with BBD, we found a significant association with sedentary lifestyle in all models tested, with an OR = 3.03 (95% CI 1.69-5.42) in the fully adjusted model. In the same way, in the fully adjusted model %BF was significantly associated to risk for BBD (OR = 0.54, 95% CI 0.30-0.98). Similar to results found in other populations, our data suggest that physical activity is an important, independent protective factor for the risk of developing BC and BBD in low-income women from an admixed population.