Abstract 3925: Crown-like structures and adipocyte size in fat tissue adjacent to breast tumor reflect parameters of obesity, dyslipidemia and serum high-sensitivity C-reactive protein
Authors: Vaysse Charlotte , Thune Inger , Garred Øystein , Muller Catherine , Schlichting Ellen , Fjeldheim Frøydis , McTiernan Anne , Frydenberg Hanne , Husøy Anders , Lundgren Steinar , Fagerland Morten W , Wist Erik A , Lømo Jon 
Published: July 2016

Background: Adult weight gain and obesity have consistently been associated with breast cancer development but the biological mechanisms operating remain unclear. Adipose tissue may develop low-grade inflammation, observed as apoptotic adipocytes surrounded by macrophages forming characteristic crown-like structures (CLS). We questioned whether CLS and adipocyte size in breast fat tissue are biomarkers of patient's body fat distribution, dyslipidemia and serum high-sensitivity C-reactive protein (hs-CRP), factors associated with breast cancer development.

Material and Methods: Among 55 women, aged 35-75 years, with newly diagnosed invasive breast cancer (stage I/II), measurements of body composition: waist to hips ratio (WHR), body mass index (BMI, kg/m2) and total fat percentage (DEXA,%) were assessed. Concentrations of lipids (cholesterol, triglycerides) and hs-CRP were determined in fasting serum blood samples. Surgical specimens of breast tumours with surrounding fat tissue were examined in Haematoxylin Eosin and CD68 stained slides to assess the size of adipocytes (μm) and CLS density (CLS/cm2). We used linear regression models to study the association between mammary adipose tissue parameters, body composition, serum lipids and inflammatory markers.

Results: The breast cancer patients had the following means: age at diagnosis, 55.2 years, BMI, 25.2 kg/m2, WHR, 0.88, truncal fat, 38.1%, total cholesterol, 5.76 mmol/l, triglycerides, 1.19 mmol/l and hs-CRP 1.75 mg/L. The mean tumour size was 16.3 mm, 93% of tumors were estrogen receptor positive and 82% were progesterone receptor positive. Mean adipocyte size was 68.0 μm and mean CLS density was 0.12 CLS/cm2. Adipocyte size and CLS density were positively associated with BMI (padipocytes = 0.004, pCLS-density = 0.008), WHR (padipocytes = 0.003, pCLS-density = 0.009) and truncal fat (padipocytes&lt;0.001, pCLS-density = 0.005). Overweight/obese patients (BMI ≥25 kg/m2) compared with normal weighted patients, had higher of cholesterol (p = 0.016), triglyceride (p&lt;0.001), hs-CRP (p = 0.001) and had higher levels of CLS density (p = 0.002) and larger adipocytes (p = 0.003).

Conclusion: Breast adipose tissue markers such as adipocyte size and CLS, reflecting local low-grade inflammation, were positively associated with excess weight, truncal fat, dyslipidemia and a high level of hs-CRP. In addition to the systemic effect, it is conceivable that fat tissue inflammation in the vicinity of the breast cancer can influence events in a paracrine manner. These findings point to important biomarkers in breast tissue that may co-exist with serum biomarkers associated with breast cancer development.

Citation Format: Charlotte Vaysse, Inger Thune, Øystein Garred, Catherine Muller, Ellen Schlichting, Frøydis Fjeldheim, Anne McTiernan, Hanne Frydenberg, Anders Husøy, Steinar Lundgren, Morten W Fagerland, Erik A Wist, Jon Lømo. Crown-like structures and adipocyte size in fat tissue adjacent to breast tumor reflect parameters of obesity, dyslipidemia and serum high-sensitivity C-reactive protein. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3925.