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      Current biomarkers of canine mammary tumors

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          Abstract

          Mammary tumors are the second most common neoplasia in dogs. Due to the high similarity of canine mammary tumors (CMT) to human breast cancers (HBC), human biomarkers of HBC are also detectable in cases of CMT. The evaluation of biomarkers enables clinical diagnoses, treatment options and prognosis for bitches suffering from this disease. The aim of this article is to give a short summary of the biomarkers of CMT based on current literature. Very promising biomarkers are miRNAs, cancer stem cells, and circulating tumor cells, as well as mutations of the breast cancer 1 gene (BRCA1) and breast cancer 2 gene (BRCA2). Until now, the most studied and reliable biomarkers of CMT have remained antigen Ki-67 (Ki-67), endothelial growth factor receptor, human epidermal growth factor receptor 2 (HER-2), estrogen receptor, progesterone receptor and cyclooxygenase 1 (COX-2), which can be detected in both serum and tissue samples using different molecular methods. However, carcinoembryonic antigen and cancer antigen 15-3 (CA 15-3), while poorly studied, seem to be good biomarkers, especially for the early detection and prognosis of CMT. We will also mention the following: proliferative cell nuclear antigen, tumor protein p53 (p53), E-cadherin, vascular endothelial growth factor, microRNAs, cancer stem cells and circulating tumor cells, which can also be useful biomarkers. Although many studies have been conducted so far, the estimation of biomarkers in cases of CMT is still not a common practice, and more detailed research should be done.

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          Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival.

          We reported previously that >or=5 circulating tumor cells (CTC) in 7.5 mL blood at baseline and at first follow-up in 177 patients with metastatic breast cancer (MBC) were associated with poor clinical outcome. In this study, additional follow-up data and CTC levels at subsequent follow-up visits were evaluated. CTCs were enumerated in 177 MBC patients before the initiation of a new course of therapy (baseline) and 3 to 5, 6 to 8, 9 to 14, and 15 to 20 weeks after the initiation of therapy. Progression-free survival (PFS) and overall survival (OS) times were calculated from the dates of each follow-up blood draw. Kaplan-Meier plots and survival analyses were done using a threshold of >or=5 CTCs/7.5 mL at each blood draw. Median PFS times for patients with or=5 CTC, median PFS from these same time points was significantly shorter: 2.7, 1.3, 1.4, 3.0, and 3.6 months, respectively. Median OS for patients with 18.5 months. For patients with >or=5 CTC, median OS from these same time points was significantly shorter: 10.9, 6.3, 6.3, 6.6, and 6.7 months, respectively. Median PFS and OS times at baseline and up to 9 to 14 weeks after the initiation of therapy were statistically significantly different. Detection of elevated CTCs at any time during therapy is an accurate indication of subsequent rapid disease progression and mortality for MBC patients.
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            MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer

            Dysregulation of microRNAs (miRNAs) is involved in the initiation and progression of several human cancers, including breast cancer (BC), as strong evidence has been found that miRNAs can act as oncogenes or tumor suppressor genes. This review presents the state of the art on the role of miRNAs in the diagnosis, prognosis, and therapy of BC. Based on the results obtained in the last decade, some miRNAs are emerging as biomarkers of BC for diagnosis (i.e., miR-9, miR-10b, and miR-17-5p), prognosis (i.e., miR-148a and miR-335), and prediction of therapeutic outcomes (i.e., miR-30c, miR-187, and miR-339-5p) and have important roles in the control of BC hallmark functions such as invasion, metastasis, proliferation, resting death, apoptosis, and genomic instability. Other miRNAs are of interest as new, easily accessible, affordable, non-invasive tools for the personalized management of patients with BC because they are circulating in body fluids (e.g., miR-155 and miR-210). In particular, circulating multiple miRNA profiles are showing better diagnostic and prognostic performance as well as better sensitivity than individual miRNAs in BC. New miRNA-based drugs are also promising therapy for BC (e.g., miR-9, miR-21, miR34a, miR145, and miR150), and other miRNAs are showing a fundamental role in modulation of the response to other non-miRNA treatments, being able to increase their efficacy (e.g., miR-21, miR34a, miR195, miR200c, and miR203 in combination with chemotherapy).
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              CA 15-3: uses and limitation as a biomarker for breast cancer.

              CA 15-3 which detects soluble forms of MUC-1 protein is the most widely used serum marker in patients with breast cancer. Its main use is for monitoring therapy in patients with metastatic disease. In monitoring therapy in this setting, CA 15-3 should not be used alone but measured in conjunction with diagnostic imaging, clinical history and physical examination. CA 15-3 is particularly valuable for treatment monitoring in patients that have disease that cannot be evaluated using existing radiological procedures. CA 15-3 may also be used in the postoperative surveillance of asymptomatic women who have undergone surgery for invasive breast cancer. In this setting, serial determination can provide median lead-times of 5-6 months in the early detection of recurrent/metastatic breast cancer. It is unclear however, whether administering systemic therapy based on this lead-time improves patient outcome. Consequently, expert panels disagree on the utility of regularly measuring CA 15-3 in the postoperative surveillance of asymptomatic women following a diagnosis of breast cancer. The main limitation of CA 15-3 as a marker for breast cancer is that serum levels are rarely increased in patients with early or localized disease. Copyright © 2010 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                ilonakaszak@gmail.com
                aannaruszczak@gmail.com
                szymon.kanafa@gmail.com
                kamil.j.kacprzak@gmail.com
                magdalena_krol@hotmail.com
                piotr_jurka@sggw.pl
                Journal
                Acta Vet Scand
                Acta Vet. Scand
                Acta Veterinaria Scandinavica
                BioMed Central (London )
                0044-605X
                1751-0147
                29 October 2018
                29 October 2018
                2018
                : 60
                : 66
                Affiliations
                [1 ]ISNI 0000 0001 1955 7966, GRID grid.13276.31, Department of Small Animal Diseases with Clinic, Veterinary Medicine Faculty, , Warsaw University of Life Sciences, ; Nowoursynowska 166, 02-787 Warsaw, Poland
                [2 ]ISNI 0000 0001 1955 7966, GRID grid.13276.31, Department of Physiological Sciences, Veterinary Medicine Faculty, , Warsaw University of Life Sciences, ; Nowoursynowska 166, 02-787 Warsaw, Poland
                Author information
                http://orcid.org/0000-0003-2735-3992
                Article
                417
                10.1186/s13028-018-0417-1
                6206704
                30373614
                b22a4600-b380-4895-a67c-906c72904cf6
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 5 March 2018
                : 20 October 2018
                Funding
                Funded by: KNOW (Leading National Research Centre) Scientific Consortium
                Award ID: KNOW-2015/CB/PR-1/29
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2018

                Veterinary medicine
                biomarkers,bitch,canine mammary gland,canine mammary tumors,dog,human breast cancer,neoplasia,veterinary oncology

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