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Breast Cancer Res. 2019 Feb 6;21(1):21. doi: 10.1186/s13058-019-1109-0.

Exosomal miRNA profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy.

Author information

1
Liquid biopsy and metastasis research group, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government PTS, Granada, Avenida de la Ilustración 114, 18016, Granada, Spain.
2
Laboratory of Genetic Identification, Legal Medicine and Toxicology Department, Faculty of Medicine, University of Granada, Avenida de la Investigación, 11, 18071, Granada, Spain.
3
Comprehensive oncology division, Clinical University Hospital, Virgen de las Nieves-San Cecilio, Av. de las Fuerzas Armadas, 2, 18014, Granada, Spain.
4
Bioinformatics Unit, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government PTS. Granada, Avenida de la Ilustración, 114, 18016, Granada, Spain.
5
Thoracic Medical Oncology, Early Clinical Trials, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC), 22 S. Greene Street, Baltimore, 21201, USA.
6
DestiNA Genomics Ltd, 7-11 Melville St, Edinburgh, EH3 7PE, UK.
7
Liquid biopsy and metastasis research group, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government PTS, Granada, Avenida de la Ilustración 114, 18016, Granada, Spain. mjose.serrano@genyo.es.
8
Comprehensive oncology division, Clinical University Hospital, Virgen de las Nieves-San Cecilio, Av. de las Fuerzas Armadas, 2, 18014, Granada, Spain. mjose.serrano@genyo.es.

Abstract

BACKGROUND:

Breast cancer patients under neoadjuvant chemotherapy includes a heterogeneous group of patients who eventually develop distal disease, not detectable by current methods. We propose the use of exosomal miRNAs and circulating tumor cells as diagnostic and predictive biomarkers in these patients.

METHODS:

Fifty-three breast cancer women initially diagnosed with localized breast cancer under neoadjuvant chemotherapy were prospectively enrolled in this study. However, six of them were later re-evaluated and diagnosed as metastatic breast cancer patients by PET-CT scan. Additionally, eight healthy donors were included. Circulating tumor cells and serum exosomal miRNAs were isolated from blood samples before and at the middle of neoadjuvant therapy and exosomal miRNA levels analyzed by qPCR.

RESULTS:

Before neoadjuvant therapy, exosomal miRNA-21 and 105 expression levels were higher in metastatic versus non-metastatic patients and healthy donors. Likewise, higher levels of miRNA-222 were observed in basal-like (p = 0.037) and in luminal B versus luminal A (p = 0.0145) tumor subtypes. Exosomal miRNA-222 levels correlated with clinical and pathological variables such as progesterone receptor status (p = 0.017) and Ki67 (p = 0.05). During neoadjuvant treatment, exosomal miRNA-21 expression levels directly correlated with tumor size (p = 0.039) and inversely with Ki67 expression (p = 0.031). Finally, higher levels of exosomal miRNA-21, miRNA-222, and miRNA-155 were significantly associated with the presence of circulating tumor cells.

CONCLUSION:

Liquid biopsies based on exosomal miRNAs and circulating tumor cells can be a complementary clinical tool for improving breast cancer diagnosis and prognosis.

KEYWORDS:

Cancer diagnosis; Cancer prognosis; Circulating tumor cells; Conservative surgery; Exosomes; Localized breast cancer; Neoadjuvant chemotherapy; microRNA

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