Abstract 3135: Notch 1 and notch 4 biomarker expression in triple-negative invasive breast cancer
Authors: Speiser Jodi J. , Foreman Kimberly , Drinka Eva K. , Godellas Constantine , Perez Claudia , Ersahin Cagatay , Salhadar Alia , Rajan Praba 
Published: June 2012

BACKGROUND: Triple-negative breast cancer (TNBC) is a high-grade tumor showing lack of expression of estrogen and progesterone receptors and human epidermal growth factor receptor (HER-2/neu). Unlike hormone receptor and HER-2/neu positive breast carcinomas, there is no targeted therapy for TNBC. The objective of this study is to investigate Notch 1 and Notch 4 biomarker expression in TNBC and to correlate the expression with known prognostic factors.

DESIGN: We performed a retrospective chart review of 29 TNBC during 1998-2007. Data collected included age at diagnosis, histological type and grade, Ki67 proliferation rate, and patient survival status. Formalin-fixed paraffin embedded tissue blocks from each TNBC was selected. Notch 1 and Notch 4 expression were analyzed by immunohistochemical method (Santa Cruz Biotechnology Inc, USA). The intensity of staining for Notch 1 and 4 expressions and the sub-cellular localization of these receptors (cytoplasmic or nuclear) in tumor epithelial cells and vascular endothelial cells were noted. Only strong cytoplasmic and/or nuclear staining was documented as positive for Notch expression. Student's t test and chi-square test were applied for data analysis.

RESULTS: Age of the patients ranged from 37 to 83 years (mean 57.7). Twenty-seven tumors were infiltrating ductal carcinomas (93.1%) and 2 were infiltrating papillary carcinomas (6.9%). Twenty-one cases were grade 3 (72.4%), 7 were grade 2 (24.2%) and one was grade 1 (3.4%). Unfavorable Ki67 proliferation rate (&gt;20%) was seen in 26 (90%), borderline rate (10-20%) in 2 (6.9%) and favorable rate (&lt;10%) in one (3.1%). Notch 1 expression was evaluable in 25 and Notch 4 in 29 cases. Notch 1 expression was present in 25/25 (100%) cases in tumor cells and in vascular endothelial cells. Notch 4 was expressed in tumor cells in 21/29 (73%) and in vascular endothelial cells in 29/29 (100%). Notch 4 expression was negative in tumor cells in 8/29 (27%) cases. Notch 1 and Notch 4 expression in tumor cells and in vascular endothelial cells are correlated with tumor grade (p&lt;0.05) and Ki67 proliferation rate (p&lt;0.05) in TNBC. Follow-up period ranged from 4-9 years (mean 5.3). Twenty-one patients are alive and well (72.4%), 2 are alive with disease (6.9%), 4 patients died of disease (13.8%), and 2 patients died of causes unrelated to disease (6.9%).

CONCLUSION: This study demonstrates that (1) majority of triple-negative invasive breast cancers are morphologically high grade infiltrating ductal carcinomas with high Ki 67 proliferation rate, (2) both Notch 1 and Notch 4 receptors are over-expressed in tumor cells and in vascular endothelial cells in majority of this molecular subset of breast carcinoma, and (3) this subtype is associated with high overall survival rate with the currently available treatment. Targeting Notch signaling with gamma secretase inhibitors needs to be explored to further improve the survival rate of TNBC patients.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3135. doi:10.1158/1538-7445.AM2011-3135