Inflammation and Increased Aromatase Expression Occur in the Breast Tissue of Obese Women with Breast Cancer

Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Cancer Prevention Research (Impact Factor: 4.44). 06/2011; 4(7):1021-9. DOI: 10.1158/1940-6207.CAPR-11-0110
Source: PubMed


Obesity is a risk factor for the development of hormone receptor-positive breast cancer in postmenopausal women and has been associated with an increased risk of recurrence and reduced survival. In humans, obesity causes subclinical inflammation in visceral and subcutaneous adipose tissue, characterized by necrotic adipocytes surrounded by macrophages forming crown-like structures (CLS). Recently, we found increased numbers of CLS, activation of the NF-κB transcription factor, and elevated aromatase levels and activity in the mammary glands of obese mice. These preclinical findings raised the possibility that the obesity → inflammation axis is important for the development and progression of breast cancer. Here, our main objective was to determine if the findings in mouse models of obesity translated to women. Breast tissue was obtained from 30 women who underwent breast surgery. CLS of the breast (CLS-B) was found in nearly 50% (14 of 30) of patient samples. The severity of breast inflammation, defined as the CLS-B index, correlated with both body mass index (P < 0.001) and adipocyte size (P = 0.01). Increased NF-κB binding activity and elevated aromatase expression and activity were found in the inflamed breast tissue of overweight and obese women. Collectively, our results suggest that the obesity → inflammation → aromatase axis is present in the breast tissue of most overweight and obese women. The presence of CLS-B may be a biomarker of increased breast cancer risk or poor prognosis.

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Available from: Kotha Subbaramaiah, May 13, 2014
    • "Androgens such as T are known to play a significant role in obesity, glucose homeostasis, and lipid metabolism (Saad and Gooren, 2011). Obesity and metabolic diseases have been shown to increase the incidence of breast cancer (Eliassen et al., 2006), increase aromatase expression in breast tissue (Morris et al., 2011), worsen the outcome of hormone-receptor-positive breast cancer (Sparano et al., 2010), and reduce responsiveness to endocrine therapy (Pfeiler et al., 2011). Also, it has been reported that obesity promotes breast cancer by modifying insulin and the insulin-like growth factor (IGF) axis and by changing circulating levels of cytokines and adipokines (Roberts et al., 2010). "
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    • "Increase in WAT mass, thus, leads into increased peripheral conversion of androgens to estrogens . Moreover, obesity-associated inflammatory factors upregulate aromatase gene expression in WAT of women (Morris et al., 2011; Subbaramaiah et al., 2012), indicating that low-grade inflammation further contributes to increased estrogen biosynthesis in WAT of obese individuals. Very little, however, is known about the regulation of CYP19A1 gene expression, or the effects of locally produced estrogens in male WAT. "
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    • "In this exploratory study we aimed to ascertain whether salivary methylation of the CYP19A1 and PPARG promoters was related to age at breast or pubic hair development in girls, both independently and in concert with body size. In light of the current literature, we anticipated overweight girls with CYP19A1 hypomethylation and PPARG hypermethylation might be predisposed to early breast development [33-35], and those with PPARG hypermethylation to early pubic hair development [9,16]. "
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