Organochlorine concentrations in adipose tissue and survival in postmenopausal, Danish breast cancer patients

2018 ◽  
Vol 163 ◽  
pp. 237-248 ◽  
Author(s):  
Nina Roswall ◽  
Mette Sørensen ◽  
Anne Tjønneland ◽  
Ole Raaschou-Nielsen
2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12533-e12533
Author(s):  
Constantinos Savva ◽  
Charles N Birts ◽  
Stéphanie A Laversin ◽  
Alicia Lefas ◽  
Jamie Krishnan ◽  
...  

e12533 Background: Obesity is associated with breast cancer development and worse survival. Obesity can initiate, promote, and maintain systemic inflammation via metabolic reprogramming of macrophages that encircle adipocytes, termed crown-like structures (CLS). In breast cancer patients, CLS are present in 36-50% of patients and have been associated with anthropometric parameters. Here we focus on HER2+ breast cancer. The role of adiposity in HER2+ breast cancer is conflicting which may be attributed to the tumour heterogeneity. Adiposity has also been shown to affect the local immune environment of solid tumours. However, the prognostic significance of CLS in HER2+ breast cancer is still unknown. Methods: We investigated the prognostic significance of CLS in a cohort of 219 patients with primary HER2+ breast cancer who were diagnosed between 1982 to 2012 in Southampton General Hospital. This cohort includes 76 HER2+ trastuzumab naïve patients and 143 HER2+ patients treated with adjuvant trastuzumab. We stained FFPE tumour samples for the expression of CD68, CD16 and CD32B on CLS and correlated these to clinical outcomes. CLS were defined as CLS within distant adipose tissue, CLS within the adipose-tumour border (B-CLS) and intratumoural CLS. CLS were quantified manually in full face sections by two independent scorers and descriptive and Cox regression analysis was carried out. Results: A total of 201 tumours were suitable for CLS analyses. The median follow-up was 34.74 months (range, 0.43-299.08). In the trastuzumab naive cohort, B-CLS≤1 and B-CLS > 1 were present in 37 (52.11%) and 34 (47.89%), respectively. In the trastuzumab treated cohort, B-CLS≤1 were identified in 69 (53.08%) and B-CLS > 1 were found in 61 (46.92%) of the tumours. CLS were more commonly found in the adipose-tumour border (60.89%) rather than in the distant adipose tissue (36.14%) or intratumorally (14.36%). The presence of any CLS was significantly associated with BMI≥25 kg/m2 (p = 0.018). There was strong evidence of association between CD68+CD32B+ B-CLS and BMI≥25 kg/m2 (p = 0.007). Co-expression of CD16 and CD32B by B-CLS was more frequent in patients with BMI≥25 kg/m2 (p = 0.036). Survival analysis showed shorter time to metastatic disease in patients with CD68+ B-CLS > 1 (p = 0.011) in the trastuzumab treated cohort. Subgroup analysis revealed that in the BMI≥25 kg/m2 group, patients with CD68+ B-CLS > 1 had shorter time to metastatic disease compared to patients with B-CLS≤1 (p = 0.004). Multivariate cox regression showed that B-CLS > 1 is an independent prognostic factor for shorter time to metastatic disease in patients with primary HER2+ breast cancer that received adjuvant trastuzumab (HR 6.81, 95%CI (1.38-33.54), p = 0.018). Conclusions: B-CLS can be potentially used as a predictive biomarker to optimize the stratification and personalisation of treatment in HER2-overexpressed breast cancer patients.


2019 ◽  
Vol 8 (9) ◽  
pp. 1358 ◽  
Author(s):  
Lee ◽  
Kim ◽  
Lee ◽  
Han ◽  
Lee ◽  
...  

This study aimed to evaluate the association between abdominal-to-gluteofemoral adipose tissue (AT) distribution and recurrence-free survival (RFS) in breast cancer patients. Staging F-18 fluorodexoyglucose (FDG) positron emission tomography/computed tomography (PET/CT) images of 336 women with breast cancer were retrospectively analyzed. From CT images, the volume and CT-attenuation of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT), and gluteofemoral AT were measured and the ratio of abdomen-to-gluteofemoral AT volume (AG volume ratio) was calculated. The relationships between adipose tissue parameters and RFS were assessed. Through univariate analysis, abdominal SAT volume, gluteofemoral AT volume, and AG volume ratio were significantly associated with RFS. An increase in abdominal SAT volume and AG volume ratio were associated with an increased risk of recurrence, whereas increased gluteofemoral AT volume was associated with a decreased risk of recurrence. On multivariate analysis, abdominal SAT volume, gluteofemoral AT volume, and AG volume ratio were found to be significant predictors of RFS after adjusting for clinic-histological factors. Irrespective of obesity, patients with a high AG volume ratio showed a higher recurrence rate than those with a low AG volume ratio. Increased abdominal SAT volume and decreased gluteofemoral AT volume were related to poor RFS in breast cancer patients.


1996 ◽  
Vol 7 (6) ◽  
pp. 591-595 ◽  
Author(s):  
Zhenrong Zhu ◽  
Markku Parviainen ◽  
Satu M�nnist� ◽  
Pirjo Pietinen ◽  
Matti Eskelinen ◽  
...  

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Martin C. Chang ◽  
Zohreh Eslami ◽  
Marguerite Ennis ◽  
Pamela J. Goodwin

AbstractCrown-like structures of the breast (CLS-B), defined by the clustering of macrophages (identified using CD68 immunohistochemical staining) to surround a dying adipocyte, are a sign of adipose-tissue inflammation. In human cohorts, CLS-B positively correlates with older age, obesity, dyslipidemia and higher levels of glucose, insulin, C-reactive protein and IL-6. In an existing cohort of early-stage breast cancer patients, CLS-B were identified using H&E stained histologic sections (hCLS-B), and by CD68 immunohistochemistry (CD68 + CLS-B). We examined associations of H&E and CD68-detected CLS-B with clinicopathologic features using χ2 tests, with metabolic factors using Wilcoxon rank sum tests and with disease free and overall survival using Cox regression models. hCLS-B were detected in 59 of 163 patients with slides (36.2%) and CD68 + CLS-B in 37 of 119 patients with paraffin blocks (31.1%). hCLS-B were positively correlated with higher weight (p = 0.003), BMI (p = 0.0008) and C-reactive protein (p = 0.045). CD68 + CLS-B were positively correlated with higher weight (p = 0.006), BMI p = 0.001), leptin (p = 0.034), insulin (p = 0.008) and Homeostasis Model Assessment (p = 0.027). CD68 + CLS-B were associated with poor distant disease-free with a hazard ratio (HR) of 2.81, 95% confidence interval (CI) 1.20–6.57, and overall survival with HR 3.97 (1.66–9.48), while hCLS-B were not associated with either: HR for distant recurrence 0.59 (0.26–1.30); HR for death 1.04 (0.50–2.16). The presence of hCLS-B and of CD68 + CLS-B were associated with obesity; CD68 + CLS-B were associated with insulin resistance and adverse prognosis. Similar patterns were not seen for hCLS-B. Research is needed to understand the biologic basis for these differences.


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