ABSTRACT
PURPOSE: To determine whether marrow fat fraction (FF) is correlated with postmenopausal breast cancer risk and clinicopathological characteristics of breast cancer. METHODS: Fifty-six patients with newly diagnosed and histologically confirmed postmenopausal breast cancer and 56 healthy controls underwent serologic test and magnetic resonance spectroscopy-based FF measurements. Data were analyzed by logistic multivariate regression models to determine the independent predictors of breast cancer risk and clinicopathological characters of breast cancer. RESULTS: Patients with breast cancer had higher FF than that of the controls. Marrow FF showed positive association with serum leptin levels (r = 0.607, P < .001) in the cases, but no relationship was found in the controls. In the univariate analysis, both levels of leptin and marrow FF were significantly associated with breast cancer risk and clinicopathological characteristics of breast cancer. In the multivariable model with adjustment for established breast cancer risk factors, serum leptin was a significant predictor of breast cancer risk (OR 1.746; 95% CI, 1.226-2.556) and clinicopathological characteristics of breast cancer including TNM, tumor size, lymph node status, and histological grade (OR 1.461-1.695); but when marrow FF was additionally added to the regression model, marrow FF but not leptin levels was observed to be an independent risk factor for breast cancer risk (OR 1.940; 95% CI, 1.306-2.910) and clinicopathological characteristics of breast cancer (OR 1.770-1.903). CONCLUSION: Marrow adiposity is a predictor of postmenopausal breast cancer risk and clinicopathological characteristics of breast cancer.
Subject(s)
Adipose Tissue/pathology , Adiposity , Bone Marrow/pathology , Breast Neoplasms/diagnosis , Magnetic Resonance Spectroscopy/methods , Adipose Tissue/diagnostic imaging , Bone Marrow/diagnostic imaging , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/etiology , Case-Control Studies , Female , Follow-Up Studies , Humans , Middle Aged , Obesity/complications , Postmenopause , Prognosis , Risk FactorsABSTRACT
Bisphenol A diglycidyl ether (BADGE), a PPARγ2 antagonist, has been shown to inhibit marrow adipogenesis and promote bone formation in intact animals. We investigated the impact of BADGE on a new and more clinically relevant physiological model, the ovariectomized (OVX) rat model. Forty female Wistar rats were divided into four treatment groups for 12 wk (n = 10/group): sham+vehicle, sham+BADGE, OVX+vehicle, and OVX+BADGE. Postmortem analyses included MRI, micro-CT, serological test, histomorphometry, biomechanical tests, RT-PCR, and Western blot. Overall, OVX induced a sequential marrow fat expansion accompanied by bone deterioration. Compared with OVX controls, BADGE reduced fat fraction of the distal femur by 36.3%, adipocyte density by 33.0%, adipocyte size by 28.6%, adipocyte volume percentage by 57.8%, and adipogenic markers PPARγ2 and C/EBPα by â¼50% in OVX rats. Similar results were observed in sham rats vs. vehicle. BADGE could promote bone quality in sham rats; however, BADGE did not significantly improve trabecular microarchitecture, biomechanical strength, and dynamic histomorphometric parameters except for trabecular separation in OVX rats. We concluded that early BADGE treatment at a dose of 30 mg/kg attenuates marrow adiposity in ovary-intact and OVX rats and stimulates bone formation in ovary-intact rats but does not significantly rescue bone quality in OVX rats.
