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The poor outcomes associated with mammary carcinomas (MCs) in dogs and cats in terms of locoregional recurrence, distant metastasis and survival, highlight the need for better management of mammary cancers in small animals. By contrast, the outcomes of women with breast cancer (BC) have dramatically improved during the last 10 years, notably thanks to new therapeutic strategies. The aim of this article was to imagine what could be the future of therapy for dogs and cats with MCs if it became inspired from current practices in human BC. This article focuses on the importance of taking into account cancer stage and cancer subtypes in therapeutic plans, on locoregional treatments (surgery, radiation therapy), new developments in endocrine therapy, chemotherapy, PARP inhibitors and immunotherapy. Ideally, multimodal treatment regimens would be chosen according to cancer stage and cancer subtypes, and according to predictive factors that are still to be defined. [ABSTRACT FROM AUTHOR]

Abstract: Due to the abundance of muscle, intravascular administration seems required for efficient gene or cell therapy of muscular dystrophy. Here, we examined the skeletal muscle microvasculature to assess if it is altered with dystrophin deficiency. Image analysis of capillaries was performed in three muscles of one- to ten-month-old golden retriever muscular dystrophy (GRMD) dogs and compared with healthy controls. In the gracilis muscle (and in the biceps brachii muscle) of 4- to 10-month-old GRMD dogs, the microvessel density (445±47 microvessels per mm2), the capillary to fiber ratio (111±26 capillaries per 100 myofibers), and the mean intercapillary distance (49±3μm), were similar in affected and control dogs. The sartorius cranialis muscle in GRMD dogs showed microvessel depletion and increased intercapillary distance, but unaltered capillary to fiber ratio, relative to the controls. The mean diameter of microvessels and the total vascular area were higher in GRMD muscles than in control ones. In severely affected GRMD muscles at 7–10 months of age, fibrosis was associated with decreased microvessel density, increased intercapillary distance and microvessel diameter, but normal capillary to fiber ratio and total vascular area. [Copyright &y& Elsevier]

Pigeon circovirus infection (PiCV) was diagnosed by light and transmission electron microscopy in 15 birds from five lofts in western France. Histopathological findings were suggestive of primary bursotropism of pigeon circovirus, followed by secondary systemic spread from the bursa of Fabricius, particularly to non-bursal lymphoid organs. The last stage of the disease was associated with various secondary (particularly bacterial) infections. In situ detection of apoptosis in the bursa of Fabricius indicated that PiCV was concomitant with an increase in bursal lymphocytic apoptotic events related to viral infection and leading to severe acquired immunosuppression. [ABSTRACT FROM AUTHOR]

Numerous studies have described the prognostic factors of canine and feline mammary carcinomas (MCs), that is, variables that predict patient survival after diagnosis. But how does survival estimation evolve in patients that escaped early death from their cancer? In human oncology, conditional survival (CS), the probability of surviving X further years when cancer patients have already survived Y years, is used to analyse cancer outcomes in a long‐term perspective. In this cohort of 344 dogs and 342 cats with surgically removed stage I to III invasive MCs, with a minimal follow‐up of 2 years, we calculated the 1‐year CS, that is, the probability for patients that have survived 1 year, to survive or to die from cancer during the subsequent year. The 1‐year conditional specific survival probabilities were 59% and 48% at diagnosis of invasive MC respectively in dogs and cats, and 80% and 52% in 1‐year surviving dogs and cats respectively, suggesting that 1‐year surviving dogs were relatively protected from cancer‐related death, whereas feline MCs remained life‐threatening cancers for longer periods of time. Among the most significant parameters associated with CS in surviving dogs and cats were the nodal stage and lymphovascular invasion, as well as patient age, cancer stage and margin status in surviving dogs. By comparison, tumour size and the histological grade did not significantly alter CS probabilities in surviving dogs and cats. Conditional survival may be considered a very interesting tool for veterinary practitioners to estimate the likely outcome of cancer survivors. [ABSTRACT FROM AUTHOR]

Background: Invasive mammary carcinomas that spontaneously develop in female cats are associated with high mortality, and resemble the most aggressive human breast cancers, especially triple-negative breast cancer (TNBC). Transcriptome studies showed that TNBCs are a heterogeneous group that includes a potentially hormone-dependent subtype named luminal-AR. Some authors proposed an immunohistochemical definition of the luminal-AR subtype, which is not only positive for Androgen Receptor (AR), but also either positive for the transcription factor Forkhead box A1 (FOXA1), or negative for basal markers. The objectives of this study were to describe AR and FOXA1 expressions in feline mammary carcinomas (FMCs), their prognostic value, and if their coexpression could define a "luminal-AR" subtype of triple-negative mammary carcinomas in cats.Methods: In a previously described retrospective cohort of 180 female cats with FMCs, with a 2-year follow-up post-mastectomy, we assessed AR, FOXA1, ER, PR, Ki-67, HER2, and CK14 expressions by automated immunohistochemistry.Results: Of the 180 FMCs, 57 (32%) were luminal; i.e., ER and/or PR positive, and 123 (68%) were triple-negative (ER-, PR- and HER2-) FMCs. AR overexpression (found in 33 cases/180, 18%) and FOXA1 index ≥1% (64/180, 36%) were associated with a longer disease-free interval, overall survival, and cancer-specific survival in cats with FMC. Analysis of AR, FOXA1 and CK14 coexpression in triple-negative FMCs showed that AR+ triple-negative FMCs were heterogeneous: there existed an AR+ FOXA1+ CK14- subgroup (n = 7) associated with a better cancer-specific survival by multivariate survival analysis (HR = 0.26, 95% CI: 0.07-0.89, p = 0.03) compared to AR+ FOXA1-CK14+ triple-negative FMCs (n = 46) (HR = 1.00), independently of the pathologic tumor size and pathologic nodal stage. The non-basal-like subtype of triple-negative FMCs that coexpresses AR and FOXA1 (the AR+ FOXA1+ CK14- subgroup) could represent the equivalent of the luminal-AR subgroup of human triple-negative breast cancer.Conclusions: We identified an AR+ FOXA1+ CK14- subgroup of triple-negative FMCs that might correspond to the luminal-AR subgroup of human triple-negative breast cancers. Cats with FMC may be interesting spontaneous animal models to investigate new strategies targeting the androgen receptor, especially in the aggressive subtype of AR+ basal-like triple-negative mammary carcinomas with loss of FOXA1 expression (the AR+ FOXA1-CK14+ subgroup). [ABSTRACT FROM AUTHOR]

Background: Dogs spontaneously develop invasive mammary carcinoma with a high prevalence of the triple-negative (TN) subtype (lack of ER-Estrogen Receptor and PR-Progesterone Receptor expression, lack of HER2-Human Epidermal Growth Factor Receptor 2 overexpression), making this animal model relevant for investigating new therapeutic pathways. Insulin-like growth factor Type-1 receptor (IGF1R) is frequently overexpressed in primary human breast cancers, with a growing role in the TN phenotype. The purpose of this study was to investigate the Dog as a candidate model for IGF1R-overexpressing mammary carcinoma.Methods: 150 bitches with canine mammary carcinoma (CMC) and a known 2-year follow-up were retrospectively included. IGF1R expression was assessed by immunohistochemistry (IHC) using a similar scoring system as for HER2 in breast cancer. The prognostic value of the IGF1R expression was assessed in terms of overall and specific survival as well as disease-free interval (DFI).Results: 47 CMC (31 %) were classified as luminal and 103 (69 %) as triple-negative (TN-CMC). 41 % of CMC overexpressed IGF1R (IHC score 3+) of which 76 % were TN-CMC and 62 % grade III. IGF1R overexpression was associated with aggressive features including lymphovascular invasion, histological grade III, low ER expression and the TN phenotype. Univariate and multivariate analyses revealed that IGF1R overexpression was associated with shorter overall and specific survivals and shorter DFI in TN-CMC.Conclusions: IGF1R overexpression is common and related to a poor outcome in canine invasive mammary carcinoma, particularly in the triple negative subtype, as in human breast cancer. Preclinical studies using the Dog as a spontaneous animal model could be considered to investigate new therapies targeting IGF1R in triple-negative breast cancer. [ABSTRACT FROM AUTHOR]

In the last decade, advances in molecular biology have provided evidence of the genotypic heterogeneity of melanoma. We analysed BRAF, NRAS and c- KIT alterations in tissue samples from 63 stage III/ IV melanoma patients and autologous cell-lines, using either allele-specific or quantitative PCR. The expression of BRAF V600E protein was also investigated using an anti- BRAF antibody in the same tissue samples. 81% of FFPE samples and tumor cell-lines harboured a genetic alteration in either BRAF (54%) or NRAS (27%) oncogenes. There was a strong concordance (100%) between tissue samples and tumor cell-lines. The BRAF V600E mutant-specific antibody showed high sensitivity (96%) and specificity (100%) for detecting the presence of a BRAF V600E mutation. The correlation was of 98% between PCR and immunohistochemistry results for BRAF mutation. These results suggest that BRAF and NRAS mutation status of tumor cells is not affected by culture conditions. [ABSTRACT FROM AUTHOR]

Background: Cats spontaneously develop invasive mammary carcinomas with high clinical aggressiveness, and are considered relevant animal models for human breast cancer. Bcl-2 is an anti-apoptotic pro-survival protein, whose expression is associated with a favorable outcome in human breast cancer. The aim of our study was to determine the frequency of Bcl-2 expression in feline invasive mammary carcinomas (FMCs), its relationship with other clinicopathologic variables, and its prognostic value. This retrospective study included 180 FMCs, diagnosed in female cats treated by surgery only, with a 2-year follow-up post-mastectomy. Bcl-2, ER, PR, Ki-67, HER2, and CK5/6 expression were determined by automated immunohistochemistry. A receiver-operating-characteristic curve was used to set the threshold for Bcl-2 positivity. Results: The cohort comprises 32% (57/180) luminal FMCs defined by ER and/or PR positivity, and 68% (123/180) triple-negative FMCs (negative for ER, PR, and HER2). Bcl-2 expression was considered as positive when at least 65% of tumor cells were immunohistochemically stained. Thirty-one out of 180 FMCs (17%) were Bcl-2-positive. There was no significant association between Bcl-2 expression, and the tumor size, nodal stage, histological grade, or ER, PR, Ki-67, HER2, and CK5/6 expression. By multivariate survival analysis (Cox proportional-hazards regression), Bcl-2 positivity in FMCs was associated with longer disease-free interval (p = 0.005, HR = 0.38), overall survival (p = 0.028, HR = 0.61), and cancer-specific survival (p = 0.019, HR = 0.54) independently of other powerful prognostic factors such as pathologic tumor size, pathologic nodal stage, and distant metastasis. The positive prognostic value of Bcl-2 was confirmed in both luminal FMCs, of which 9/57 (16%) were Bcl-2-positive, and in basal-like triple-negative (ER–, PR–, HER2–, CK5/6+) FMCs, of which 14/76 (18%) were Bcl-2-positive. Conclusions: Compared to human breast cancer, Bcl-2 positivity in feline invasive mammary carcinomas is also associated with better outcome, but is less common, and not associated with ER, PR, and HER2 expression. Cats with spontaneous Bcl-2-positive FMCs could be useful in preclinical trials evaluating anti-Bcl-2 strategies for chemoresistant luminal or triple-negative breast cancers. [ABSTRACT FROM AUTHOR]