Table 1. Clinical and experimental studies in breast cancer and crown-like structures.
| Reference | Model | Target | Results |
|---|---|---|---|
| Morris et al., 2011 [53] | Human | Aromatase activity; adipocyte size; serum inflammation marker; CLS-B index | CLS-B correlated with BMI and adipocyte size |
| Subbaramaiah et al., 2011 [91] | Animals | NF-kB Activation; TNF-α, IL-1β, and COX-2 levels; aromatase activity; CLS | Obesity-inflammation-aromatase axis in the mammary gland and WAT, and its association with CLS, increased risk of ER breast cancer |
| Subbaramaiah et al., 2012 [75] | Human | Aromatase activity; CLS-B index | CLS-B index as an improved correlation marker of breast cancer and obesity |
| Iyengar et al., 2015 [60] | Human | CLS-B presence; Circulating inflammatory mediators | CLS-B is associated with metabolic syndrome and worse breast cancer prognosis |
| Cowen et al., 2015 [64] | Animal | Effect of a high-fat/high-calorie diet on mammary carcinogenesis | Breast adipose tissue inflammation induced by diet increases tumor vascular density |
| Seo et al., 2015 [63] | Animal; in vitro and human | Role of obesity in interstitial fibrosis in mammary fat | α-SMA levels correlated with CLS-B contribute to increased levels of matrix extracellular remodeling in obesity |
| Koru-Sengul et al., 2016 [62] | Human | Association between the number of TAM and/or CLS and ethnicities | Race is associated with the numbers of TAM and CLS in breast cancer |
| Mullooly et al., 2017 [89] | Human | CLS-B and sex steroid hormones in breast adipose tissue | CLS were not related to hormone levels or tumor characteristics, but were associated with hormone ratios |
| Vaysse et al., 2017 [90] | Human | CLS-B associated with mammary adipocyte size, body composition, and serum biomarkers | CLS was associated with systemic markers |
| Brown et al., 2017 [61] | Human | Effect of menopause on breast aromatase expression in relation to BMI, CLS and systemic markers of metabolic dysfunction | Postmenopausal women had higher BMI and presence of CLS than did premenopausal women |
| Cha et al., 2018 [76] | Human | Macrophage infiltration and identification of CLS status | CD68+ and/or CD163+ macrophages and CLS are present in adipose tissue near the breast cancer lesion |
| Iyengar et al., 2018 [59] | Human | CLS compared in Taiwanese vs Caucasian women | Compared with Caucasians, Taiwanese women had larger breast adipocytes despite lower BMI after adjusting for BMI and menopausal status |
| Greenlee et al., 2019 [79] | Human | Inflammation and BMI in Hispanic/Latina breast cancer patients | Prevalence of CLS-B was associated with Hispanic/Latina patients |
| Springer et al., 2019 [73] | Human and mice | Extracellular matrix affects macrophage phenotype | Fibrotic extracellular matrix remodeling promotes a TAM phenotype of macrophages in CLS |
CLS-B = crown-like structures in breast; BMI = body mass index; TNF-α = tumor necrosis factor α; IL = interleukin; COX-2 = cyclooxygenase-2; WAT = white adipose tissue; ER = estrogen receptor; α-SMA = α-smooth muscle actin; TAM = tumor-associated macrophage.