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Transl Oncol. 2017 Aug;10(4):589-598. doi: 10.1016/j.tranon.2017.05.006. Epub 2017 Jun 27.

Evaluation of the Prognostic Value of RANK, OPG, and RANKL mRNA Expression in Early Breast Cancer Patients Treated with Anthracycline-Based Adjuvant Chemotherapy.

Author information

1
Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece.
2
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece; Translational Research Section, Hellenic Cooperative Oncology Group, Athens, Greece.
3
Section of Biostatistics, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece.
4
STRATYFIER Molecular Pathology GmbH, Cologne, Germany.
5
Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
6
Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece.
7
Second Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece.
8
Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece.
9
Department of General Surgery, Breast Division, St Luke's Hospital, Thessaloniki, Greece.
10
Oncology Unit, Hippokration Hospital, Athens, Greece.
11
Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece.
12
Breast Unit, Metropolitan Hospital, Piraeus, Greece.
13
Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, Athens, Greece.
14
Second Department of Medical Oncology, Hygeia Hospital, Athens, Greece.
15
Department of Medical Oncology, 424 Army General Hospital, Thessaloniki, Greece.
16
Second Department of Prop. Surgery, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
17
First Department of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
18
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece; Aristotle University of Thessaloniki, Thessaloniki, Greece. Electronic address: fountzil@auth.gr.

Abstract

BACKGROUND:

Prevention of bone metastases is a major issue for breast cancer patients, as it would improve quality of life in a population where long survival is anticipated.

PATIENTS AND METHODS:

Early breast cancer patients, who had been treated with anthracycline-based chemotherapy within two randomized trials, were included in the study. We evaluated, by quantitative reverse transcription-polymerase chain reaction, 819 formalin-fixed paraffin-embedded tumor tissue samples for mRNA expression of RANK, OPG, and RANKL, as well as their ratios, for potential prognostic significance for the development of bone metastases and also for disease-free survival (DFS) and overall survival.

RESULTS:

Median age was 52.7years, whereas 54.2% of the patients were postmenopausal and 78.3% estrogen receptor/progesterone receptor positive. After a median follow-up of 119.9months, 226 patients (27.6%) had died and 291 patients (35.5%) had disease progression. Low mRNA expression of RANKL was associated with postmenopausal status and greater number of positive lymph nodes (P=.002 and P<.001, respectively). In the univariate analysis, low RANKL mRNA expression was found to be an unfavorable factor for DFS [hazard ratio (HR)=1.33, 95% confidence interval (CI) 1.05-1.68, Wald's P=.018] and bone metastasis-free survival (HR=1.67, 95% CI 1.09-2.56, P=.018), although it did not retain its significance in the multivariate analysis.

CONCLUSIONS:

Low RANKL mRNA expression in early breast cancer patients is of prognostic significance for increased risk for relapse and bone metastases and might potentially guide clinical decision-making for the use of anti-RANKL agents in the treatment of early breast cancer patients at high risk for metastatic spread, provided that our findings are validated in independent cohorts.

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