Abstract

IntroductionCirculating microRNAs (miRNAs) exhibit remarkable stability and may serve as biomarkers in several clinical cancer settings. The aim of this study was to investigate changes in the levels of specific circulating miRNA following breast cancer surgery and evaluate whether these alterations were also observed in an independent data set.MethodsGlobal miRNA analysis was performed on prospectively collected serum samples from 24 post-menopausal women with estrogen receptor-positive early-stage breast cancer before surgery and 3 weeks after tumor resection using global LNA-based quantitative real-time PCR (qPCR).ResultsNumbers of specific miRNAs detected in the samples ranged from 142 to 161, with 107 miRNAs detectable in all samples. After correction for multiple comparisons, 3 circulating miRNAs (miR-338-3p, miR-223 and miR-148a) exhibited significantly lower, and 1 miRNA (miR-107) higher levels in post-operative vs. pre-operative samples (p<0.05). No miRNAs were consistently undetectable in the post-operative samples compared to the pre-operative samples. Subsequently, our findings were compared to a dataset from a comparable patient population analyzed using similar study design and the same qPCR profiling platform, resulting in limited agreement.ConclusionsA panel of 4 circulating miRNAs exhibited significantly altered levels following radical resection of primary ER+ breast cancers in post-menopausal women. These specific miRNAs may be involved in tumorigenesis and could potentially be used to monitor whether all cancer cells have been removed at surgery and/or, subsequently, whether the patients develop recurrence.

Highlights

  • Circulating microRNAs exhibit remarkable stability and may serve as biomarkers in several clinical cancer settings

  • Breast cancer follow-up for the purpose of early detection of local or metastatic recurrence is predominantly based on clinical examination and mammography, and previously suggested tumor markers, such as CA 15.3, CA 27.29 and carcinoembryonic antigen (CEA), are not recommended in the routine follow-up after initial treatment [3]

  • Global miRNA analysis was performed on serum from 24 postmenopausal patients with estrogen receptor (ER)-positive and HER2-negative early-stage breast cancer prior to tumor resection as well as 3 weeks after surgery using LNA-based qRT-PCR (Table 1)

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Summary

Introduction

Circulating microRNAs (miRNAs) exhibit remarkable stability and may serve as biomarkers in several clinical cancer settings. After completion of adjuvant therapy, follow-up care focuses on detecting recurrent disease in the hope of improving long-term survival. Breast cancer staging is based on tumor size, lymph node status, and the presence or absence of metastatic disease. Axillary lymph node status in stage I and II is the strongest prognostic factor, but 25% of patients without axillary lymph-node metastasis will have a systemic relapse. Breast cancer follow-up for the purpose of early detection of local or metastatic recurrence is predominantly based on clinical examination and mammography, and previously suggested tumor markers, such as CA 15.3, CA 27.29 and carcinoembryonic antigen (CEA), are not recommended in the routine follow-up after initial treatment [3]

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