Maats, M.E.M. (2012) Immunohistochemical biomarkers and their relation with (disease-free) survival in BRCA1-like and non-BRCA1-like subgroups in triple-negative breast cancer. thesis, Medicine.
![[img]](https://umcg.studenttheses.ub.rug.nl/style/images/fileicons/text.png) |
Text
MaatsMEM.pdf Restricted to Registered users only Download (1MB) |
Abstract
Background: Triple-negative breast cancer (TNBC) accounts for 10-20% of all breast tumours and has a poor prognosis. Because of the absence of hormone receptors and HER2 overexpression there is no targeted therapy for this subgroup yet and the only treatment option remains chemotherapy. With better understanding of the pathways that lead to the triple-negative state and adequate subgrouping by means of finding an accurate immunohistochemical (IHC) biomarker profile, we might be able to better predict prognosis and develop specific targeted therapies. This could improve the survival in this subgroup of breast cancer patients. In this retrospective study we examined the expression of different immunohistochemical biomarkers and their relation with (disease-free) survival in BRCA1-like and non-BRCA1-like subgroups in triple-negative breast cancer. Patients and methods: 101 triple-negative patients with a known Multiplex Ligation-dependent Probe Amplification (MLPA) result from the study of Oonk et al were included. Immunohistochemistry on tissue micro-arrays (TMAs) of the original tumour tissue was performed, with 91 triple-negative patients remaining for our study. 63 patients had a tumour with a BRCA1-like profile, which were considered as homologous recombination deficient (HRD). The remaining 28 patients had a tumour with a non-BRCA1-like profile, considered as non-homologous recombination deficient (NHRD). The expression pattern of several biomarkers was compared in both subgroups and marker expression was also compared with relapse free survival (RFS), disease specific survival (DSS) and overall survival (OS). Results: Several differences in biomarker expression in subgroups of TNBC were identified. Specific IHC expression profiles for the BRCA1-like group (p53/IGF1Rmem-positive) and non-BRCA1-like group (VEGF-positive; p53/IGF1Rmem-negative) could be defined. Most tumours were of the basal-like phenotype. In survival analysis, only large tumour size was of negative prognostic value. No biomarker was of prognostic significance in the total patient group. Conclusion: In a previous study, subgroups of TNBC according to their DNA profile did not show differences in survival. In our study, we could not discriminate a set of biomarkers that can better predict prognosis. We found distinct immunohistochemical features for BRCA1-like and non-BRCA1-like groups, so in daily routine both groups can possibly be classified by using immunohistochemistry. These IHC expression profiles might become indicative for specific targeted therapy in TNBC subgroups. As TNBC has a distinct relapse pattern, current TNM staging is not sufficient to predict outcome and make optimal treatment decisions. In the near future, possibly, IHC expression profiles from the tumour of the individual patient could be taken into account, for optimal treatment of triple-negative breast cancer.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Supervisor and Imholz, Dr. A.L.T. and Location: Medical Oncology, Deventer Hospital and Pathology, Deventer Hospital and Pathology, Antoni van Leeuwenhoek |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:07 |
| Last Modified: | 25 Jun 2020 11:07 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2727 |
Actions (login required)
 |
View Item |