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Abstract 1416: An animal model to study the effects of primary tumor excision on metastatic potential and organ-tropism of residual breast cancer cells
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Abstract 1416: An animal model to study the effects of primary tumor excision on metastatic potential and organ-tropism of residual breast cancer cells

Yun Zhang, Danielle Jernigan, Mercedes Lioni, Fernando Garcia and Alessandro Fatatis
Cancer research (Chicago, Ill.), v 72(8_Supplement), pp 1416-1416
15 Apr 2012
DOI: https://doi.org/10.1158/1538-7445.AM2012-1416

Abstract

Abstract Because of constant improvements in early detection, the majority of breast cancer patients are diagnosed when still in a localized or regional stage and considered to be viable candidates for breast-conserving surgery or lumpectomy. As only 37% of breasts are found tumor-free following initial lumpectomy, between 22 and 59% of patients currently need re-intervention because positive or close margins are detected. In addition, re-excision or adjuvant therapies, such as local irradiation, are normally started several weeks or even months after primary surgery. During this period, the stroma at the site of tumor removal, which is characterized by altered angiogenesis, immune cells infiltration and activation of cancer-associated fibroblasts, may be selecting for cancer stem phenotypes, increasing metastatic potential and promoting the dissemination to specific secondary organs. This study aims to: 1) establish whether surgery on primary breast tumors leads to the emergence of cellular phenotypes with higher malignancy, associated with an increase in local growth, invasiveness and metastatic potential; 2) determine whether breast surgery alters the organ-tropism of residual cancer cells. For our experiments, BALB/c mice were inoculated in the mammary fat pad with 4T1 murine breast cancer cells and developed tumors that were either allowed to progress or surgically excised. Approximately 50% of animals in the surgery group presented with local recurrence, although all the excised tumors had positive margins. Local recurrences showed higher Ki-67 staining compared to their respective primary tumors and these data were in agreement with human samples of primary and recurrent breast tumors. Interestingly, the overall survival of mice in the control and surgery with recurrence groups were similar. Furthermore, macroscopic lung metastases were detected in the control and local recurrence groups, whereas mice without post-surgery recurrence failed to develop lung metastatic lesions. Finally, differences in the dissemination and growth of 4T1 cells to brain and bone between control, surgery plus recurrence and surgery without recurrence groups were investigated. 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 1416. doi:1538-7445.AM2012-1416

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