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      Canine as a Comparative and Translational Model for Human Mammary Tumor

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          Abstract

          Despite the advances in research and treatment of human breast cancer, its incidence rate continues to increase by 0.5% per year, and the discovery of novel therapeutic strategies for specific subtypes of human breast cancer remains challenging. Traditional laboratory mouse models have contributed tremendously to human breast cancer research. However, mice do not develop tumors spontaneously; consequently, genetically engineered mouse models or patient-derived xenograft models are often relied upon for more sophisticated human breast cancer studies. Since human breast cancer develops spontaneously, there is a need for alternative, yet complementary, models that can better recapitulate the features of human breast cancer to better understand the molecular and clinical complexities of the disease in developing new therapeutic strategies. Canine mammary tumors are one such alternative model that share features with human breast cancer, including prevalence rate, subtype classification, treatment, and mutational profiles, all of which are described in this review.

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          Most cited references72

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          Breast cancer

          Breast cancer is the most frequent malignancy in women worldwide and is curable in ~70-80% of patients with early-stage, non-metastatic disease. Advanced breast cancer with distant organ metastases is considered incurable with currently available therapies. On the molecular level, breast cancer is a heterogeneous disease; molecular features include activation of human epidermal growth factor receptor 2 (HER2, encoded by ERBB2), activation of hormone receptors (oestrogen receptor and progesterone receptor) and/or BRCA mutations. Treatment strategies differ according to molecular subtype. Management of breast cancer is multidisciplinary; it includes locoregional (surgery and radiation therapy) and systemic therapy approaches. Systemic therapies include endocrine therapy for hormone receptor-positive disease, chemotherapy, anti-HER2 therapy for HER2-positive disease, bone stabilizing agents, poly(ADP-ribose) polymerase inhibitors for BRCA mutation carriers and, quite recently, immunotherapy. Future therapeutic concepts in breast cancer aim at individualization of therapy as well as at treatment de-escalation and escalation based on tumour biology and early therapy response. Next to further treatment innovations, equal worldwide access to therapeutic advances remains the global challenge in breast cancer care for the future.
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            pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up

            Morphological assessment of the degree of differentiation has been shown in numerous studies to provide useful prognostic information in breast cancer, but until recently histological grading has not been accepted as a routine procedure, mainly because of perceived problems with reproducibility and consistency. In the Nottingham/Tenovus Primary Breast Cancer Study the most commonly used method, described by Bloom & Richardson, has been modified in order to make the criteria more objective. The revised technique involves semiquantitative evaluation of three morphological features--the percentage of tubule formation, the degree of nuclear pleomorphism and an accurate mitotic count using a defined field area. A numerical scoring system is used and the overall grade is derived from a summation of individual scores for the three variables: three grades of differentiation are used. Since 1973, over 2200 patients with primary operable breast cancer have been entered into a study of multiple prognostic factors. Histological grade, assessed in 1831 patients, shows a very strong correlation with prognosis; patients with grade I tumours have a significantly better survival than those with grade II and III tumours (P less than 0.0001). These results demonstrate that this method for histological grading provides important prognostic information and, if the grading protocol is followed consistently, reproducible results can be obtained. Histological grade forms part of the multifactorial Nottingham prognostic index, together with tumour size and lymph node stage, which is used to stratify individual patients for appropriate therapy.
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              Translation of new cancer treatments from pet dogs to humans.

              Naturally occurring cancers in pet dogs and humans share many features, including histological appearance, tumour genetics, molecular targets, biological behaviour and response to conventional therapies. Studying dogs with cancer is likely to provide a valuable perspective that is distinct from that generated by the study of human or rodent cancers alone. The value of this opportunity has been increasingly recognized in the field of cancer research for the identification of cancer-associated genes, the study of environmental risk factors, understanding tumour biology and progression, and, perhaps most importantly, the evaluation and development of novel cancer therapeutics.
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                Author and article information

                Journal
                J Breast Cancer
                J Breast Cancer
                JBC
                Journal of Breast Cancer
                Korean Breast Cancer Society
                1738-6756
                2092-9900
                February 2023
                30 January 2023
                : 26
                : 1
                : 1-13
                Affiliations
                [1 ]The Jackson Laboratory for Genomic Medicine, Farmington, USA.
                [2 ]The Jackson Laboratory, Sacramento, USA.
                [3 ]Department of Veterinary Clinical Medicine, University of Illinois, Urbana, USA.
                [4 ]Cancer Center at Illinois, University of Illinois, Urbana, USA.
                Author notes
                Correspondence to Charles Lee. The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032, USA. Charles.Lee@ 123456jax.org
                Author information
                https://orcid.org/0000-0003-0196-1682
                https://orcid.org/0000-0002-9819-9227
                https://orcid.org/0000-0002-4439-9987
                https://orcid.org/0000-0003-2510-7050
                https://orcid.org/0000-0001-7317-6662
                Article
                10.4048/jbc.2023.26.e4
                9981990
                36762784
                5152ee45-d824-4697-bf69-ff179fab985c
                © 2023 Korean Breast Cancer Society

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 31 October 2022
                : 13 December 2022
                : 13 December 2022
                Categories
                Review Article

                Oncology & Radiotherapy
                canine mammary tumor,canine somatic and germline mutation profiles,canine-patient derived xenograft,comparative oncology model

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