Abstract 392: The role of post surgical inflammation in tumor progression in breast cancer

Abstract

Abstract Introduction The process of chronic inflammation inducing malignant transformation is well known and recognized in several disease states, including ulcerative colitis (colorectal carcinoma), chronic wounds (squamous cell carcinoma), and hepatitis B infection (hepatocellular carcinoma) as common examples. Recent evidence suggests that this process may be relevant in other tumor types and may be influenced by inflammation arising secondary to interventional procedures. The purpose of this study is to investigate the potential role of inflammatory mediators resulting from the post-surgical healing process on tumor proliferation and progression to metastasis in breast cancer. Methods We used MMTV-PyV MT female mice (transgenic mice expressing the middle T antigen of the polyomavirus under the control of the MMTV promoter/enhancer) as a mouse model of human epidermal breast cancer. Mice underwent a surgical punch biopsy (2 mm) in the center of the tumor, or underwent the same procedure (transient anesthesia) without biopsy. Mice were paired according to the tumor size at the time of biopsy. Mice were then euthanized 8 days after biopsy, and lungs were harvested and histologically examined for the presence of micrometastases. To further evaluate the effect of inflammation in the development of metastases, a separate subset of mice were treated with ibuprofen versus vehicle (placebo control) for three days after biopsy. Results No substantial difference in the primary tumor growth was observed after biopsy between the various groups. However, a greater number of metastases were found in the lungs of mice that underwent biopsy relative to the number in mice that did not receive biopsy. The number of metastases was reduced in the set of mice receiving ibuprofen treatment following the biopsy procedure (9.3 vs. 25 p<0.05). Conclusion Our study provides evidence to suggest that inflammatory mediators arising secondary to the healing process may stimulate tumor proliferation and metastasis. These findings may hold significance for the timing of breast cancer treatment following diagnostic needle biopsy, as well as for the potential impact of excisional biopsy on the outcome of patients with breast cancer. Further research into the mechanisms of this interaction may help to increase our understanding of breast cancer biology and may yield new strategies (e.g. anti-inflammatory medication) to optimize treatment and outcome. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 392. doi:1538-7445.AM2012-392