Evaluation and correlation of risk recurrence in early breast cancer assessed by Oncotype DX®, clinicopathological markers and tumor cell dissemination in the blood and bone marrow

Aktas,Bahriye; Bankfalvi,Agnes; Heubner,Martin; Kimmig,Rainer; Kasimir‑Bauer,Sabine

doi:10.3892/mco.2013.174

Evaluation and correlation of risk recurrence in early breast cancer assessed by Oncotype DX®, clinicopathological markers and tumor cell dissemination in the blood and bone marrow

Authors:
- Bahriye Aktas
- Agnes Bankfalvi
- Martin Heubner
- Rainer Kimmig
- Sabine Kasimir‑Bauer
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Affiliations: Department of Gynecology and Obstetrics, University of Duisburg‑Essen, University Hospital of Essen, Essen, North Rhine‑Westphalia D‑45122, Germany, Department of Pathology, University of Duisburg‑Essen, University Hospital of Essen, Essen, North Rhine‑Westphalia D‑45122, Germany
Published online on: September 2, 2013 https://doi.org/10.3892/mco.2013.174
Pages: 1049-1054

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Abstract

The Oncotype DX® assay is a validated genomic test that predicts the likelihood of breast cancer recurrence, patient survival within ten years of diagnosis and the benefit of chemotherapy in early‑stage, node‑negative, estrogen receptor‑positive breast cancer. Further markers of recurrence include disseminated tumor cells (DTCs) in the bone marrow (BM) and circulating tumor cells (CTCs) in the blood, particularly stemness‑like tumor cells (slCTCs). In this study, Oncotype DX, DTCs, CTCs and slCTCs were used to evaluate the risk of recurrence in 68 patients with human epidermal growth factor receptor 2‑negative, early‑stage breast cancer. Formalin‑fixed, paraffin‑embedded tissue sections were analyzed for the expression of 16 cancer genes and 5 reference genes by Oncotype DX, yielding a recurrence score (RS). G2 tumors were evaluated for urokinase‑type plasminogen activator (uPA)/plasminogen activator inhibitor type 1 (PAI1) and Ki‑67. Two BM aspirates were analyzed by immunocytochemistry for DTCs using the pan‑cytokeratin antibody A45‑B/B3. CTCs and slCTCs in the blood were detected using the AdnaTest BreastCancer, AdnaTest EMT and the AdnaTest TumorStemCell. Oncotype DX was performed in 68 cases, yielding a low RS in 30/68 patients (44%), an intermediate RS in 29/68 patients (43%) and a high RS in 9/68 patients (13%). DTCs were detected in 19/68 patients (28%), CTCs in 13/68 patients (19%) and slCTCs in 26/68 (38%) patients. Moreover, 8/68 patients (12%) with G2 tumors were positive for uPA, 6/68 (9%) for PAI1 and 21/68 (31%) for Ki‑67. Ki‑67, progesterone receptor (PR) and G3 tumors were significantly correlated with RS (P<0.001; P=0.006; and P=0,002, respectively), whereas no correlation was identified between DTCs, CTCs, slCTCs and RS. Ki‑67 may support therapeutic decisions in cases where Oncotype DX is not feasible. Larger patient cohorts are required to estimate the additional detection of DTCs and CTCs for the determination of risk recurrence.

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