Background: Tumor budding is a phenomenon associated with epithelial mesenchymal transition and correlates with tumor invasiveness and metastasis in colon cancer. In breast cancer this histomorphological feature has not yet been determined. In this study we investigated the prognostic value of peritumoral budding (PTB) and intratumoral budding (ITB) in invasive ductal breast cancer and its correlation with lymph node status. Method: Two pathologists counted tumor buds within the tumor (ITB) and at the periphery (PTB) of 90 primary invasive ductal breast cancers. ITB and PTB were scored on whole tissue sections stained with a PanCK antibody. Budding was defined as isolated single cancer cells or microscopic cell clusters composed of ≥1 or up to 5 cells. A tumor was designated to have high-grade budding if it had an average of >10 buds. PTB and ITB were then correlated with pathological features of breast cancer. Results: Forty-eight percent (n=43) and 50% (n=45) were considered high-grade for either ITB or PTB, respectively. High-grade PTB was significantly (p=0.0044) associated with lymph node metastasis and ITB was significantly (p=0.0018) associated with hormone receptor positive tumors. ITB and PTB were frequent in Her2 negative (50% and 53%) tumors and breast cancer with higher T-category >T3 (57%). Neither PTB nor ITB showed an association with tumor grade or proliferation index as measured by Mib-1 staining. Conclusion: For the first time, we report that PTB is a strong (p=0.0044) predictive tumor feature of lymph node metastasis in invasive ductal breast cancer. The association of PTB with metastatic disease may be due to an increased occurrence of lymph vessels found at the tumor periphery. Additional studies are ongoing to determine if tumor budding can select for more aggressive subtypes of invasive breast cancer.

Citation Format: Mafalda Trippel, Katrin Pfaltz, Bodour Salhia, André Grogg, Inti Zlobec, Coya F. Tapia. Tumor budding is a predictive feature for lymph node metastasis in invasive ductal breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3460. doi:10.1158/1538-7445.AM2013-3460