Showing papers by "Marguerite Ennis published in 2017"
TL;DR: The prevalence of the metabolic syndrome and diabetes/pre-diabetes was significantly higher in BC survivors than in controls group, notably in those with lower levels of physical activity.
Abstract: We studied metabolic factors, diabetes, and anthropometric measurements at diagnosis and long-term follow-up (LTFU), mean 12.5 years post-diagnosis, in breast cancer (BC) survivors, and compared their status at LTFU to that of age-matched women without BC. Diet and physical activity were also assessed. 535 non-diabetic BC patients treated at three University of Toronto hospitals were followed prospectively; 285 surviving patients, without distant recurrence, participated in a LTFU study. A control group of 167 age-matched women without BC was recruited from a mammogram screening program at one of the hospitals. Change over time was analyzed using paired t tests, and comparisons between BC survivors and controls used age and education (AE)-adjusted regression models. Median weight gain in BC survivors was 2.00 kg (p < 0.0001); BMI, glucose, insulin, homeostasis model assessment (HOMA), and total cholesterol increased modestly but significantly. Waist circumference, glucose, and triglycerides were higher in LTFU BC survivors versus controls. BC survivors had significantly greater prevalence of diabetes/pre-diabetes versus controls (33 vs. 20.4%, AE-adjusted odds ratio (OR) 1.59, p = 0.050). This effect was restricted to those with lower levels of physical activity (<56 metabolic equivalent (MET)-hours/week: OR 2.70 versus 0.94 for those with higher physical activity, interaction p = 0.034). At LTFU, BC survivors were more physically active than at diagnosis (median increase 28 MET-hours/week interquartile range −14.8 to 82), and compared to controls (median 68.2 vs. 44 MET-hours/week, p < 0.0001). The prevalence of the metabolic syndrome and diabetes/pre-diabetes was significantly higher in BC survivors than in controls group, notably in those with lower levels of physical activity. Enhanced diabetes/metabolic syndrome screening and promotion of physical activity may be warranted in BC survivors.
14 citations
TL;DR: Although leptin and BMI did not modulate OB-R expression, downstream signaling ( e.g. Akt, ERK) did show a BMI-dependent effect, albeit of limited magnitude, which suggests that leptin acts on breast cancer cells throughOB-R activation and downstream Akt/ERK signaling, without a coupled change in total OB- R expression.
Abstract: Background/Aims: Obesity is associated with a 30-50% increased risk of breast-cancer (BC) mortality, most consistently in estrogen receptor (ER) positive disease, through unclear mechanisms. Leptin is a multi-functional protein with key actions on adipose tissue. In pre-clinical studies, leptin stimulates the growth, survival, and progression of BC cells through both estrogen dependent and other (e.g. JAK/STAT, PI3K/Akt, MAPK) pathways. Leptin has also been associated with increased BC risk and poor prognosis. Our aim was to correlate tumor leptin-receptor (OB-R) expression with tissue markers of cell signaling and systemic markers of obesity, inflammation, and metabolism in a cohort of ER+/HER2- BC patients. Methods: From our biorepository, we identified ER+/HER2- BC patients having both blood and tissue samples available. Data included BMI, menopausal status, and family/cancer/medical history, tumor histology, grade, stage, and ER/PgR/HER2 status. We performed blood assays for factors related to inflammation, tumor growth, hormonal regulation, and metabolism (see below). Immunohistochemistry for OB-R, pAkt (S473), pERK (T202/Y204), and insulin-receptor (IR) was performed on archived tissue, and scored for % positive cells and intensity of staining. Allred and H-scores were calculated. Associations with OB-R scores were calculated using Pearson, Spearman, and χ 2 methods. Results: 129 patients were eligible; 69.8% were post-menopausal and mean BMI was 27.8 ± 6.5 kg/m 2 . Most tumors were no-special-type (79%), PgR+ (90%), and node-neg (78%). The tissue expression of OB-R and other markers was scorable in 118 (91%) cases. OB-R was expressed in all 118/118 cancers (Allred score range: 3 to 8; median 7, mean 6.61). High blood leptin did not downregulate OB-R (Spearman R=0), even though leptin was strongly correlated with BMI (Pearson r=0.78, p OB-R correlated with ER (Spearman R = 0.27), PgR (R=0.29), and insulin receptor (R = 0.24), weakly correlated with estradiol (Spearman, R=0.11) and fasting glucose (R=0.18), and negatively correlated with systemic IL-2 (R=-0.11) and IL-6 (R=-0.21). OB-R was not correlated with other blood markers (insulin, HOMA, PAI-1, IL-1ẞ, IL-8, VEGF, EGF, TNF-α,hsCRP, SHBG, or estrogens) or tumor grade. Conclusions: OB-R is highly expressed in breast tumor tissue even in non-obese patients. Although leptin and BMI did not modulate OB-R expression, downstream signaling ( e.g. Akt, ERK) did show a BMI-dependent effect, albeit of limited magnitude. This suggests that leptin acts on breast cancer cells through OB-R activation and downstream Akt/ERK signaling, without a coupled change in total OB-R expression. Further work is needed to elucidate the roles of inflammation, estrogens, and regulatory mechanisms within the PI3K-PTEN and Ras-MAPK cell-signaling networks. The authors wish to acknowledge the generous support of the Breast Cancer Research Foundation and Hold9Em For Life Charity Challenge. Citation Format: Chang MC, Ennis M, Dowling RJO, Stambolic V, Goodwin PJ. Leptin receptor (OB-R) in breast carcinoma tissue: Ubiquitous expression and correlation with leptin-mediated signaling, but not with systemic markers of obesity [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-02-03.
1 citations