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

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 ran...

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Published in:	Translational oncology Vol. 10; no. 4; pp. 589 - 598
Main Authors:	Timotheadou, Eleni, Kalogeras, Konstantine T., Koliou, Georgia-Angeliki, Wirtz, Ralph M., Zagouri, Flora, Koutras, Angelos, Veltrup, Elke, Christodoulou, Christos, Pentheroudakis, George, Tsiftsoglou, Aris, Papakostas, Pavlos, Aravantinos, Gerasimos, Venizelos, Vasilios, Pectasides, Dimitrios, Kosmidis, Paris, Karanikiotis, Charisios, Markopoulos, Christos, Gogas, Helen, Fountzilas, George
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-08-2017 Neoplasia Press Elsevier
Subjects:	Short communication
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The first two authors (E.T. and K.T.K.) have contributed equally to this work.
ISSN:	1936-5233 1936-5233 1944-7124
DOI:	10.1016/j.tranon.2017.05.006