Abstract CN07-02: Obesity, inflammation, and breast cancer

Abstract

Abstract Obesity is a risk factor for the development of several malignancies including hormone receptor–positive breast cancer in postmenopausal women and has been associated with an increased risk of recurrence and reduced survival. Chronic inflammation increases the risk of multiple tumor types. A link between obesity, breast inflammation and hormone receptor-positive breast cancer was previously unknown. Obesity causes subclinical inflammation in visceral and subcutaneous white adipose tissue, characterized by macrophages surrounding dead or dying adipocytes forming crown-like structures (CLS). Estrogen synthesis is catalyzed by aromatase, which is encoded by CYP19. We found increased numbers of CLS, activation of the NF-kappaB transcription factor, increased levels of pro-inflammatory mediators and elevated aromatase levels in the mammary glands of obese mice. These preclinical findings raised the possibility that the obesity-inflammation-aromatase axis is important for breast carcinogenesis. Importantly, these findings have now been translated to women. Breast tissue was obtained from women who underwent surgery. CLS of the breast (CLS-B) were found in approximately 50% of patient samples. The severity of breast inflammation correlated with both body mass index and adipocyte size. Menopause is an independent determinant of CLS-B. Consistent with our preclinical findings, increased NF-κB binding activity, increased levels of pro-inflammatory mediators 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 and is likely to contribute to the increased risk of hormone receptor-positive breast cancer. The discovery of the connection between obesity, breast inflammation and changes in the expression of genes linked to breast cancer provides a mechanistic rationale for the development of behavioral, dietary and pharmacological strategies to reduce the risk of breast cancer. Non-invasive biomarkers of adipose inflammation are needed to both identify at-risk individuals and monitor the efficacy of interventions aimed at attenuating inflamed adipose tissue. Recent progress in the development of blood biomarkers of breast adipose inflammation will be reviewed. Citation Format: Andrew J. Dannenberg. Obesity, inflammation, and breast cancer. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr CN07-02.