Plasma deoxycholic acid concentration is elevated in postmenopausal women with newly diagnosed breast cancer

Abstract

Objective: High concentrations of plasma deoxycholic acid (DCA) are found in human breast cyst fluid and it has been hypothesised that this may be related to risk of breast cancer. The aim of this pilot study was to ascertain whether plasma bile acid concentrations were greater in women with breast cancer. Design: A case -control study comparing postmenopausal women with breast cancer with healthy controls was conducted. Subjects: Twenty Caucasian postmenopausal breast cancer patients were recruited at the time of diagnosis together with 20 healthy controls matched for age and body mass index. Exclusion criteria included any treatment for breast cancer, use of hormone replacement therapy in the last 12 months, diabetes mellitus, a history of liver or gall bladder disease or abnormal liver function. Measurements: Fasting plasma bile acid concentrations were determined by gas -liquid chromatography=mass spectrometry. Results: The mean plasma DCA concentration was 52% higher (P ¼ 0.012) in patients with breast cancer compared with controls. Conclusion: These results support the hypothesis that DCA may be involved in the aetiology of breast cancer. Sponsorship: V Costarelli was the recipient of a scholarship from Harokopion Institution, Athens.

Lipids isolated from bone induce the migration of human breast cancer cells

“…Hence, bone or MG63 cell-derived DC was most likely taken up from serum and then released to the medium. The accumulation of bile acids from serum by .30-fold has been reported for breast cyst fluid and is discussed as a potential risk factor in breast cancer (6,7,12,13). We have shown that MG63 cells also take up and accumulate DC from medium, suggesting that bone tissue has similar capabilities for DC enrichment from serum.…”

“…Bile acids, another species of oxygenated cholesterol, have long been implicated in the tumorigenesis of colorectal cancer (4,5). Recent studies have shown that an increased concentration of bile acids in breast cyst fluid is indicative of a higher risk of developing breast cancer (6,7). It remained to be elucidated, however, which cell signaling pathways for tumorigenesis and breast cancer cell migration are triggered by bile acids.…”

“…The specific enrichment of deoxycholic acid and other bile acids in breast cyst fluid shows that tissues other than liver can take up and accumulate bile acids from the serum (7,12,13). Bile acids bind to the nuclear receptor farnesoid X receptor (FXR) and activate a variety of genes involved in cholesterol metabolism and transport (14-17).…”

Association between farnesoid X receptor expression and cell proliferation in estrogen receptor-positive luminal-like breast cancer from postmenopausal patients

“…Magnification bar: 10 lm as risk factors for developing breast cancer [17,18]. More recently, plasma bile acid concentrations were reported to be higher in postmenopausal women newly diagnosed with breast cancer, as compared to healthy controls matched for age and body mass index [16]. In addition, the current study reveals that chenodeoxycholic acid (CDCA) promotes the growth of MCF-7 cells.…”

“…Surprisingly, we and others have also found FXR expression in breast cancer tissue and breast cancer cell lines [13][14][15]. With regard to breast cancer development, the presence of high plasma levels of deoxycholic acid in postmenopausal breast cancer patients, as compared to healthy controls matched for age and body mass index, has been documented, suggesting that this bile acid might be involved in mammary gland carcinogenesis [16]. Moreover, accumulation of bile acids from serum has been reported in breast cyst fluid and has been discussed as a potential risk factor for developing breast cancer [17][18][19].…”