Abstract
In our previous study, intravenous (IV) injection of selenium alleviated breast cancer-related lymphedema (BCRL). This secondary analysis aimed to explore the metabolic effects of selenium on patients with BCRL. Serum samples of the selenium-treated (SE, n = 15) or the placebo-controlled (CTRL, n = 14) groups were analyzed by ultra-high-performance liquid chromatography with Q-Exactive Orbitrap tandem mass spectrometry (UHPLC-Q-Exactive Orbitrap/MS). The SE group showed a lower ratio of extracellular water to segmental water (ECW/SW) in the affected arm to ECW/SW in the unaffected arm (arm ECW/SW ratio) than the CTRL group. Metabolomics analysis showed a valid classification at 2-weeks and 107 differential metabolites were identified. Among them, the levels of corticosterone, LTB4-DMA, and PGE3—which are known anti-inflammatory compounds—were elevated in the SE group. Pathway analysis demonstrated that lipid metabolism (glycerophospholipid metabolism, steroid hormone biosynthesis, or arachidonic acid metabolism), nucleotide metabolism (pyrimidine or purine metabolism), and vitamin metabolism (pantothenate and CoA biosynthesis, vitamin B6 metabolism, ascorbate and aldarate metabolism) were altered in the SE group compared to the CTRL group. In addition, xanthurenic acid levels were negatively associated with whole blood selenium level (WBSe) and positively associated with the arm ECW/SW. In conclusion, selenium IV injection improved the arm ECW/SW ratio and altered the serum metabolic profiles in patients with BCRL, and improved the anti-inflammatory process in lipid, nucleotide and vitamin pathways, which might alleviate the symptoms of BCRL.
Highlights
Two-way ANOVA demonstrated that overweight/obesity had no interaction with the clinical improvements of lymphedema in this study (F = 0.011, p = 0.917)
Se resulted in an increased whole blood selenium level (WBSe), but showed no effects on body weight, BMI, and single-frequency bioimpedance analysis (SFBIA) ratios, consistent with our previous study [30]
The beneficial effects of Se as a treatment for Breast cancer-related lymphedema (BCRL) have been demonstrated in several clinical beneficial effects of Se as a treatment for BCRL have been demonstrated in several clinical studies, including our previous research [2,24,25,30]
Summary
Breast cancer-related lymphedema (BCRL) is a type of secondary lymphedema that stems from the disruption or obstruction of the lymphatic system after breast cancer surgery and axillary radiation therapy [1,2]. The clinical manifestation of BCRL is characterized by swelling of the upper body, especially the arms, shoulders, and necks of affected patients [3]. A meta-analysis study reported that upper limb lymphedema most frequently occurred within 2 years after a breast cancer diagnosis or surgery [4]. Another study indicated that the incidence was highest (9.8%) at 4 years, which was more than twice the incidence rate 2 years after surgery. A previous nationwide study in Denmark reported that the prevalence rate of perceived lymphedema after breast cancer treatment was approximately 65% [5]
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