Abstract 1204: Heterogeneity within triple-negative breast cancer (TNBC).
Authors: Adeoye Adewunmi O. , Youngson Bruce J. , Miller Naomi , Done Susan J. 
Published: August 2014

Background: TNBC refers to those breast cancers which are negative for ER, PR and Her2/neu overexpression, thereby unsuitable for hormone and trastuzumab therapy. Although TNBC overlap with basal-like breast cancers, these terms are not synonymous. We decided, in a single institution cohort, to develop a better understanding of the types of tumors that make up TNBC

Materials and Methods: We carried out a clinicopathological study of a cohort of 192 patients diagnosed with TNBC at the University Health Network in 2007. Patient biodata, clinical and histopathological information of proven prognostic importance was retrieved from the records. Tissue microarrays were constructed from duplicate 0.6mm cores of representative tumour tissue and stained with 9 antibodies according to recommended protocols. The TMA slides were interpreted using the Allred method except for the Ki67 staining which was interpreted by the visual estimate method of assessing proportion of nuclei taking up stains. Results were tabulated and summary statistics was done to determine proportions.

Results: The age-range is 28 - 99 years. The median and modal age group was 50 -59 years. 70.3% of the patients are aged between 40 and 69 years at the time of diagnosis. The tumour size range was 0.6cm to 16 cm. 41.67% are pT1, 51.04% are pT2 while 6.8% are pT3. Four patients had T4 tumor with skin and nipple involvement. The diagnosis was predominantly invasive ductal carcinoma (IDC) in 84.9% of patients. Metaplastic carcinoma (10.4%), pleomorphic lobular carcinoma (1.5%), and single cases of invasive lobular carcinoma (ILC), tubular, apocrine and poorly differentiated carcinoma were seen. DCIS is a prominent feature in 26.6% of the cases. The number of lymph nodes identified ranged from 0 - 46. 59.90% were in pN0 category, 16.7% in the pN1 category, pN2 - 8.3%, and 15.1% in pN3 category. Extra-nodal metastasis at diagnosis was found in 7.3% of patients. The tumour grade: Grade I - 1.55%, Grade II - 13.47% and Grade III 84.97%. CD44 was positive in 17.71%, p63 - 4.17%, p53 - 51.56%, e-cadherin - 81.77%, Vimentin - 77.60%, Cyclin D1 - 22.40%, BCL-2 - 19.27%, and androgen receptor (AR) - 5.73%. 43.75% of cases show proliferation rates of ≥15%, while 26.04% have proliferation rates of between 5% and ≤14%.

Conclusion: While a large proportion of TNBCs show a high proliferation (Ki67, Cyclin D1 and grade III), a substantial number did not show this. This study provides clues to support the current hypothesis that several mechanisms drive the carcinogenesis of TNBC, with a heterogeneous pattern of biomarker expression. Further investigation is needed to better understand the factors driving the development and progression of the different types of TNBC.

Citation Format: Adewunmi O. Adeoye, Bruce J. Youngson, Naomi Miller, Susan J. Done. Heterogeneity within triple-negative breast cancer (TNBC). [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 1204. doi:10.1158/1538-7445.AM2013-1204