Immunohistochemical biomarker profile for BRCA1-like triple-negative breast cancer.

Boes, J. (2014) Immunohistochemical biomarker profile for BRCA1-like triple-negative breast cancer. thesis, Medicine.

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Abstract

Background: The triple-negative breast cancer (TNBC) subtype, characterized by the absence of expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor, account for 15-20% of all the invasive breast cancers. Patients with TNBC have a relatively poor prognosis due to rapid tumor growth, increased likelihood of distance recurrence one to four years after diagnosis and limited therapeutic options since targeted treatment options are unavailable. TNBC frequently has a genomic profile corresponding to the profile in breast cancers of breast cancer1 (BRCA1) mutation carriers. This profile is indicative of defects in the BRCA pathway, resulting in a phenotype that is called BRCA1-like. More knowledge about the specific pathways driving the aggressive behavior of the different subtypes of TNBC is needed to improve treatment options and better predict prognosis. Methods: 118 triple-negative breast cancer patients were included. A multiplex ligation-dependant probe amplification (MLPA) test was performed to determine the presence or absence of the BRCA1-like profile. Biomarkers AR, CK5/6, CK14, c-KIT, EGFR, IGF1R, Ki67, p53, and VEGF were immunohistochemical assessed on tissue microarrays. Biomarker expression was compared in the BRCA1-like and non-BRCA1-like subgroups and the expression patterns were compared with the occurrence of events. Results: Of the tumors, 78 (66%) had a BRCA1-like profile. Patients with this profile had more positive IGF1R membranous expression and negative VEGF expression. Patients with a non-BRCA1-like profile have more often positive VEGF expression and negative IGF1R membranous expression. Almost all events had a negative AR expression (96%, p = 0.30). No prognostic biomarkers could be defined. Conclusion: We defined possible predictive markers for BRCA1-like triple-negative breast cancer, but these markers have a low negative predictive value. This immunohistochemical biomarker profile cannot differentiate both groups. We weren't able to define biomarkers that predict relapse or advanced disease of TNBC.

Item Type:	Thesis (Thesis)
Supervisor name:	Imholz, Dr. A.L.T. and Medical Oncology, Deventer Hospital and Molecular Pathology and the Netherlands Cancer Institute - and Antoni van Leeuwenhoek, Amsterdam
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:43
Last Modified:	25 Jun 2020 10:43
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/426

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