RESUMEN

Breast cancer (BC) remains a significant global health concern, with neoadjuvant chemotherapy (NACT) offering preoperative benefits like tumor downstaging and treatment response assessment. However, identifying factors influencing post-NACT treatment response and survival outcomes is challenging. Metabolomic approaches offer promising insights into understanding these outcomes. This study analyzed the serum of 80 BC patients before and after NACT, followed for up to five years, correlating with disease-free survival (DFS) and overall survival (OS). Using untargeted nuclear magnetic resonance (NMR) spectroscopy and a novel statistical model that avoids collinearity issues, we identified metabolic changes associated with survival outcomes. Four metabolites (histidine, lactate, serine, and taurine) were significantly associated with DFS. We developed a metabolite-related survival score (MRSS) from these metabolites, stratifying patients into low- and high-risk relapse groups, independent of classical prognostic factors. High-risk patients had a hazard ratio (HR) for DFS of 3.42 (95% CI 1.51-7.74; p = 0.003) after adjustment for disease stage and age. A similar trend was observed for OS (HR of 3.34, 95% CI 1.64-6.80; p < 0.001). Multivariate Cox proportional hazards analysis confirmed the independent prognostic value of the MRSS. Our findings suggest the potential of metabolomic data, alongside traditional markers, in guiding personalized treatment decisions and risk stratification in BC patients undergoing NACT. This study provides a methodological framework for leveraging metabolomics in survival analyses.

Asunto(s)

Neoplasias de la Mama , Metabolómica , Terapia Neoadyuvante , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Persona de Mediana Edad , Metabolómica/métodos , Adulto , Pronóstico , Anciano , Supervivencia sin Enfermedad , Metaboloma , Quimioterapia Adyuvante , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/metabolismo , Modelos de Riesgos Proporcionales

RESUMEN

Iron is an essential element for human health. In humans, dysregulated iron homeostasis can result in a variety of disorders and the development of cancers. Enhanced uptake, redistribution, and retention of iron in cancer cells have been suggested as an "iron addiction" pattern in cancer cells. This increased iron in cancer cells positively correlates with rapid tumor growth and the epithelial-to-mesenchymal transition, which forms the basis for tumor metastasis. However, the source of iron and the mechanisms cancer cells adopt to actively acquire iron is not well understood. In the present study, we report, for the first time, that the peptide hormone, prolactin, exhibits a novel function in regulating iron distribution, on top of its well-known pro-lactating role. When stimulated by prolactin, breast cancer cells increase CD44, a surface receptor mediating the endocytosis of hyaluronate-bound iron, resulting in the accumulation of iron in cancer cells. In contrast, macrophages, when treated by prolactin, express more ferroportin, the only iron exporter in cells, giving rise to net iron output. Interestingly, when co-culturing macrophages with pre-stained labile iron pools and cancer cells without any iron staining, in an iron free condition, we demonstrate direct iron flow from macrophages to cancer cells. As macrophages are one of the major iron-storage cells and it is known that macrophages infiltrate tumors and facilitate their progression, our work therefore presents a novel regulatory role of prolactin to drive iron flow, which provides new information on fine-tuning immune responses in tumor microenvironment and could potentially benefit the development of novel therapeutics.

Asunto(s)

Neoplasias de la Mama , Receptores de Hialuranos , Hierro , Macrófagos , Prolactina , Prolactina/metabolismo , Hierro/metabolismo , Receptores de Hialuranos/metabolismo , Macrófagos/metabolismo , Humanos , Femenino , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Animales , Ratones , Proteínas de Transporte de Catión

RESUMEN

Morphological and immunohistochemical studies of solid arrangement canine mammary carcinomas have shown that the different histological types may be characterized by proliferation of epithelial and/or myoepithelial cells. However, little is known about immunophenotypes and the importance of inflammation as prognostic factors in these neoplasms. The objective of the present study was to characterize the immunophenotype and degree of inflammation in the solid type of canine mammary neoplasm and to investigate their association with metastasis, Ki-67 index, tumour size, necrosis and survival. Sixty-five carcinomas with solid pattern, basaloid carcinomas, solid papillary carcinomas, malignant adenomyoepitheliomas (MAMEs) or malignant myoepitheliomas (MMEs) were investigated. Luminal A, luminal B HER2 negative and HER2 positive, HER2 overexpressed and triple negative immunophenotypes were immunolabelled as were Ki-67 protein and cyclooxygenase-2 (Cox-2). Histological peritumoural and intratumoural inflammatory infiltrates were graded (distribution × intensity) and the presence of necrosis identified. We found a statistical difference between histological types and immunophenotypes, with MME and MAME having a higher occurrence of luminal A, whereas most neoplasms had the luminal B HER-negative immunophenotype. There was no correlation between immunophenotype and degree of peri- and intratumoural inflammation, nodal metastasis, necrosis or tumour size. An increased degree of peri- and intratumoural inflammation was significantly associated with lymph node metastasis, and more severe intratumoural inflammation was associated with the presence of tumour necrosis. Tumour size, Ki-67 index and Cox-2 score were not associated with inflammation in either peri- or intratumoural regions. No difference was observed in survival in relation to immunophenotype or degree of inflammation, but the Cox regression model revealed that nodal metastasis influenced the risk of death.

Asunto(s)

Enfermedades de los Perros , Inmunofenotipificación , Inflamación , Neoplasias Mamarias Animales , Animales , Perros , Femenino , Neoplasias Mamarias Animales/patología , Enfermedades de los Perros/patología , Enfermedades de los Perros/inmunología , Biomarcadores de Tumor/análisis

RESUMEN

INTRODUCTION: Aspartame, invented in 1965 by GD-Searle, is an intense artificial sweetener taste approximately 200 times as sweet as sucrose and used as an additive in more than 6,000 products. Aspartame (APM) was submitted for pre-marketing safety evaluation in early 1980. The studies, performed by GD-Searle, produced controversial results. AREAS COVERED: Because of the great commercial diffusion of aspartame, in 1997 the Ramazzini Institute (RI) started a large experimental project on rodents to test the carcinogenic effects of aspartame following an experimental model with more sensitive characteristics, namely a large number of rat and mice, starting treatment from prenatal life, observation until spontaneous death. Overall, the project included studying 2270 rats and 852 mice. These studies have shown that aspartame is a carcinogenic agent in experimental animals, inducing a significant dose-related increased incidence of several types of malignant tumors and, among them, hematological neoplasia, and liver cancer. EXPERT OPINION: The results of these studies on aspartame by the Ramazzini Institute opened a real front on the evaluation of artificial sweeteners and their possible health risks. Adequate long-term carcinogenicity bioassays on other diffuse artificial sweeteners such as acesulfame-k, sucralose, saccharin, including their blends, are likewise important for public health.

Asunto(s)

Aspartame , Carcinógenos , Relación Dosis-Respuesta a Droga , Neoplasias , Edulcorantes , Aspartame/efectos adversos , Aspartame/administración & dosificación , Animales , Edulcorantes/efectos adversos , Edulcorantes/administración & dosificación , Edulcorantes/farmacología , Ratones , Neoplasias/inducido químicamente , Neoplasias/patología , Ratas , Humanos , Carcinógenos/toxicidad , Carcinógenos/administración & dosificación , Pruebas de Carcinogenicidad

RESUMEN

Breast cancer is a malignant tumor that has the highest morbidity and mortality in women worldwide. Human epidermal growth factor receptor 2 (HER2) is a key driver of breast cancer development. Therefore, accurate assessment of HER2 expression in cancer patients and timely initiation or termination of anti-HER2 treatment are crucial for the prognosis of breast cancer patients. The emergence of radiolabeled molecular probes targeting HER2 makes this assessment possible. This article describes different types of small-molecule probes that target HER2 and are used in current preclinical applications and summarizes their advantages and disadvantages.

RESUMEN

Sonodynamic therapy (SDT) has been extensively studied as a new type of non-invasive treatment for mammary cancer. However, the poor water solubility and defective biocompatibility of sonosensitizers during SDT hinder the sonodynamic efficacy. Herein, a nanoplatform has been developed to achieve high efficient SDT against mammary cancer through the host-guest interaction of ß-cyclodextrin/5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin (ß-CD-TPP) and ferrocenecarboxylic acid/chitooligosaccharides (FC-COS). Moreover, the glucose oxidase (GOx) was loaded through electrostatic adsorption, which efficiently restricts the energy supply in tumor tissues, thus enhancing the therapeutic efficacy of SDT for tumors. Under optimal conditions, the entire system exhibited favorable water solubility, suitable particle size and viable biocompatibility. This facilitated the integration of the characteristics of starvation therapy and sonodynamic therapy, resulting in efficient inhibition of tumor growth with minimal side effects in vivo. This work may provide new insights into the application of natural oligosaccharides for construct multifunctional nanocarrier systems, which could optimize the design and development of sonodynamic therapy strategies and even combination therapy strategies.

Asunto(s)

Quitosano , Oligosacáridos , Especies Reactivas de Oxígeno , Terapia por Ultrasonido , Oligosacáridos/química , Oligosacáridos/farmacología , Animales , Quitosano/química , Quitosano/farmacología , Femenino , Especies Reactivas de Oxígeno/metabolismo , Ratones , Terapia por Ultrasonido/métodos , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacología , Ratones Endogámicos BALB C , Línea Celular Tumoral , Glucosa Oxidasa/metabolismo , Glucosa Oxidasa/química , Nanopartículas/química , Quitina/química , Quitina/análogos & derivados , Quitina/farmacología , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Compuestos Ferrosos/química , Compuestos Ferrosos/farmacología , Neoplasias de la Mama/terapia , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Metalocenos/química , Metalocenos/farmacología , Porfirinas/química , Porfirinas/farmacología

RESUMEN

BACKGROUND: Little information exists about vitamin D status in bitches with mammary tumors. OBJECTIVES: To determine whether low plasma vitamin D concentrations are found in bitches with mammary tumors. ANIMALS: Eighty-five client-owned bitches with mammary tumors (n = 21 benign, n = 64 malignant) and 39 age-matched healthy bitches. METHODS: Case-control study. Plasma ionized and total calcium, phosphorus, magnesium, urea, creatinine, albumin, total proteins, alanine aminotransferase, alkaline phosphatase, parathyroid hormone (PTH), calcitriol (1,25-dihydroxyvitamin D), and 25-hydroxyvitamin D concentrations were measured in all bitches at the time of clinical diagnosis and before any treatments. Statistical analysis was performed to compare variables among groups (control, benign, and malignant). RESULTS: No significant differences were found when plasma 25-hydroxyvitamin D concentrations in bitches with malignant (148.9 [59.9] ng/mL) and benign mammary tumors (150.1 [122.3] ng/mL) were compared with control group (129.9 [54.5] ng/mL). Parathyroid hormone was significantly higher in bitches with malignant (19.9 [20.5] pg/mL), and benign mammary tumors (14.6 [14.9] pg/mL) compared with control group (7.5 [7.5] pg/mL; P < .01). Only the presence of mammary tumors (P < .01) and age (P = .04; adjusted R2 = .22) was significant in predicting PTH. CONCLUSIONS: Bitches with mammary tumors do not have low 25-hydroxyvitamin D concentrations thus vitamin D supplementation is unlikely to be useful for prevention of mammary tumors in bitches.

Asunto(s)

Enfermedades de los Perros , Neoplasias Mamarias Animales , Hormona Paratiroidea , Vitamina D , Animales , Perros , Femenino , Enfermedades de los Perros/sangre , Neoplasias Mamarias Animales/sangre , Vitamina D/sangre , Vitamina D/análogos & derivados , Estudios de Casos y Controles , Hormona Paratiroidea/sangre , Calcio/sangre , Fósforo/sangre

RESUMEN

Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are highly aggressive neoplastic diseases that share numerous characteristics. In IBC and IMC, chemotherapy produces a limited pathological response and anti-androgen therapies have been of interest for breast cancer treatment. Therefore, the aim was to evaluate the effect of a therapy based on bicalutamide, a non-steroidal anti-androgen, with doxorubicin and docetaxel chemotherapy on cell proliferation, migration, tumor growth, and steroid-hormone secretion. An IMC-TN cell line, IPC-366, and an IBC-TN cell line, SUM149, were used. In vitro assays revealed that SUM149 exhibited greater sensitivity, reducing cell viability and migration with all tested drugs. In contrast, IPC-366 exhibited only significant in vitro reductions with docetaxel as a single agent or in different combinations. Decreased estrogen levels reduced in vitro tumor growth in both IMC and IBC. Curiously, doxorubicin resulted in low efficacy, especially in IMC. In addition, all drugs reduced the tumor volume in IBC and IMC by increasing intratumoral testosterone (T) levels, which have been related with reduced tumor progression. In conclusion, the addition of bicalutamide to doxorubicin and docetaxel combinations may represent a potential treatment for IMC and IBC.

Asunto(s)

Anilidas , Proliferación Celular , Docetaxel , Neoplasias Inflamatorias de la Mama , Neoplasias Mamarias Animales , Nitrilos , Compuestos de Tosilo , Compuestos de Tosilo/farmacología , Humanos , Animales , Femenino , Nitrilos/farmacología , Nitrilos/uso terapéutico , Línea Celular Tumoral , Anilidas/farmacología , Perros , Neoplasias Inflamatorias de la Mama/tratamiento farmacológico , Neoplasias Inflamatorias de la Mama/patología , Neoplasias Inflamatorias de la Mama/metabolismo , Proliferación Celular/efectos de los fármacos , Docetaxel/farmacología , Neoplasias Mamarias Animales/tratamiento farmacológico , Neoplasias Mamarias Animales/patología , Neoplasias Mamarias Animales/metabolismo , Doxorrubicina/farmacología , Ratones , Supervivencia Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ensayos Antitumor por Modelo de Xenoinjerto , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Testosterona

RESUMEN

Neratinib, a typical small-molecule, pan-human tyrosine kinase inhibitor (TKI), has been licensed for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, the underlying pharmacological mechanism is still unknown. In the current study, we report a novel function of Neratinib by showing that its treatment stimulates senescence of the mammary cancer AU565 cells. Our results demonstrate that Neratinib induces mitochondrial injury by increasing mitochondrial reactive oxygen species (ROS) and reducing intracellular adenosine triphosphate (ATP). Also, we found that Neratinib induced DNA damage by increasing the levels of 8-Hydroxy-desoxyguanosine (8-OHdG) and γH2AX in AU565 cells. Additionally, Neratinib reduced the levels of telomerase activity after 7 and 14 days incubation. Importantly, the senescence-associated-ß-galactosidase (SA-ß-Gal) assay revealed that Neratinib stimulated senescence of AU565 cells. Neratinib decreased the gene levels of human telomerase reverse transcriptase (hTERT) but increased those of telomeric repeat-binding factor 2 (TERF2) in AU565 cells. Further study displayed that Neratinib upregulated the expression of K382 acetylation of p53 (ac-K382) and p21 but reduced the levels of sirtuin-1 (SIRT1). However, overexpression of SIRT1 abolished the effects of Neratinib in cellular senescence. These findings provide strong preclinical evidence of Neratinib's treatment of breast cancer.

Asunto(s)

Neoplasias de la Mama , Senescencia Celular , Quinolinas , Sirtuina 1 , Humanos , Sirtuina 1/metabolismo , Sirtuina 1/genética , Senescencia Celular/efectos de los fármacos , Quinolinas/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Daño del ADN/efectos de los fármacos , Telomerasa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Antineoplásicos/farmacología

RESUMEN

Mammary tumors are the most frequent type of neoplasms in intact female dogs. New therapies that target neoplastic cells without affecting normal cells are highly sought. The Bacillus anthracis toxin has been reengineered to target tumor cells that express urokinase plasminogen activators and metalloproteinases. In previous studies carried out in our laboratory, the reengineered anthrax toxin had inhibitory effects on canine oral mucosal melanoma and canine osteosarcoma cells. In this study, five canine neoplastic epithelial cell lines (four adenocarcinomas and one adenoma) and one non-neoplastic canine mammary epithelial cell line were treated with different concentrations of reengineered anthrax toxin components. Cell viability was quantified using an MTT assay and half-maximal inhibitory concentration (IC50) values. Cell lines were considered sensitive when the IC50 was lower than 5000 ng/ml. One canine mammary adenocarcinoma cell line and one mammary adenoma cell line showed significantly decreased viability after treatment, whereas the non-neoplastic cell line was resistant. We conclude that the reengineered anthrax toxin may be considered a targeted therapy for canine mammary neoplasms while preserving normal canine mammary epithelial cells.

Asunto(s)

Antígenos Bacterianos , Toxinas Bacterianas , Enfermedades de los Perros , Neoplasias Mamarias Animales , Animales , Perros , Neoplasias Mamarias Animales/tratamiento farmacológico , Toxinas Bacterianas/farmacología , Femenino , Antígenos Bacterianos/farmacología , Línea Celular Tumoral , Enfermedades de los Perros/tratamiento farmacológico , Células Epiteliales/efectos de los fármacos , Adenocarcinoma/veterinaria , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Supervivencia Celular/efectos de los fármacos , Adenoma/veterinaria , Adenoma/tratamiento farmacológico , Adenoma/patología

RESUMEN

PURPOSE: In this study, we aimed to assess the new trends in characteristics, molecular subtypes, and imaging findings of breast cancer in very young women. METHODS: We retrospectively reviewed the database of a primary breast cancer referral center in southern Iran in 342 cases of 30-year-old or younger women from 2001 to 2020. Pathologic data, including nuclear subtype and grade, tumor stage, presence of in situ cancer, imaging data including lesion type in mammogram and ultrasound, and treatment data were recorded. Descriptive statistics were applied. Differences between categorical values between groups were compared using Pearson's Chi-square test. RESULTS: The mean age was 27.89 years. The tumor type was invasive ductal carcinoma in 82 % of cases. Fourteen patients (4.4 %) had only in situ cancer, and 170 patients had in situ components (49.7 %). Molecular subtypes were available in 278 patients, including 117 (42.1 %) Luminal A, 64 (23.0 %) Luminal B, 58 (20.9 %) triple negative, and 39 (14 %) HER2 Enriched. In those with mammograms available, 63 (30.1 %) had no findings, 53 (25.3 %) had mass, 27 (12.9 %) had asymmetry, whether focal or global, 21 (10 %) had microcalcifications solely, and 45 (21.5 %) had more than one finding. Microcalcifications were significantly more common in Luminal cancers than HER2 and triple-negative cancers (p = 0.041). CONCLUSION: Our study shows the most common subtype to be Luminal A cancer, with 74 % of the tumors being larger than 2 cm at the time of diagnosis. Irregular masses with non-circumscribed margins were the most common imaging findings.

Asunto(s)

Neoplasias de la Mama , Mamografía , Ultrasonografía Mamaria , Humanos , Femenino , Estudios Retrospectivos , Adulto , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Mamografía/métodos , Ultrasonografía Mamaria/métodos , Irán/epidemiología , Adulto Joven , Mama/diagnóstico por imagen , Mama/patología , Estadificación de Neoplasias

RESUMEN

Mammary cancer is a frequent disease in female dogs, where a high proportion of cases correspond to malignant tumors that may exhibit drug resistance. Within the mammary tumor microenvironment, there is a cell subpopulation called cancer stem cells (CSCs), which are capable of forming spheres in vitro and resisting anti-tumor treatments, partly explaining the recurrence of some tumors. Previously, it has been described that spheres derived from canine mammary carcinoma cells CF41.Mg and REM 134 exhibit stemness characteristics. Melatonin has shown anti-tumor effects on mammary tumor cells; however, its effects have been poorly evaluated in canine mammary CSCs. This study aimed to analyze the effect of melatonin on the chemoresistance exhibited by stem-like neoplastic cells derived from canine mammary carcinoma to cytotoxic drugs such as doxorubicin and mitoxantrone. CF41.Mg and REM 134 cells were cultured in high-glucose DMEM supplemented with fetal bovine serum and L-glutamine. The spheres were cultured in ultra-low attachment plates in DMEM/F12 medium without fetal bovine serum and with different growth factors. The CD44+/CD24-/low phenotype was analyzed by flow cytometry. The viability of sphere-derived cells (MTS reduction) was studied in the presence of melatonin (0.1 or 1 mM), doxorubicin, mitoxantrone, and luzindole. In addition, the gene (RT-qPCR) of the multidrug resistance bombs MDR1 and ABCG2 were analyzed in the presence of melatonin. Both cell types expressed the MT1 gene, which encodes the melatonin receptor MT1. Melatonin 1 mM does not modify the CD44+/CD24-/low phenotype; however, the hormone reduced viability (p < 0.0001) only in CF41.Mg spheres, without inducing an additive effect when co-incubated with cytotoxic drugs. These effects were independent of the binding of the hormone to its receptor MT1, since, by pharmacologically inhibiting them, the effect of melatonin was not blocked. In CF41.Mg spheres, the relative gene expression of ABCG2 and MDR1 was decreased in response to the hormone (p < 0.001). These results indicate that melatonin negatively modulates the cell survival of spheres derived from CF41.Mg cells, in a way that is independent of its MT1 receptor. These effects did not counteract the resistance to doxorubicin and mitoxantrone, even though the hormone negatively regulates the gene expression of MDR1 and ABCG2.

RESUMEN

CMC is the most frequently diagnosed cancer and one of the leading causes of death in non-spayed female dogs. Exploring novel therapeutic agents is necessary to increase the survival rate of dogs with CMC. MPOBA is a BZOP derivative that has a significant anticancer effect in a human cell line. The main goal of this study was to investigate the anticancer properties of MPOBA against two CMC cell lines (REM134 and CMGT071020) using a 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, a wound healing assay, a transwell migration assay, an Annexin V-FITC apoptosis assay with a flow cytometry analysis, a mRNA expression analysis using quantitative real-time PCR (qRT-PCR), and an immunohistochemistry (IHC). According to the accumulated studies, MPOBA caused significant concentration- and time-dependent reductions in cell proliferation and cell migration and induced apoptosis in both CMC cell lines. In gene expression analysis, nine canine genes, including TP53, BCL-2, BAX, epidermal growth factor receptor (EGFR), snail transcription factor (SNAIL), snail-related zinc-finger transcription factor (SLUG), TWIST, E-cadherin, and N-cadherin, were investigated. The mRNA expression results revealed that MPOBA induced upregulation of TP53 and overexpression of the pro-apoptotic gene BAX, together with an inhibition of BCL-2. Moreover, MPOBA also suppressed the mRNA expression levels of SNAIL, EGFR, and N-cadherin and induced upregulation of E-cadherin, crucial genes related to the epithelial-to-mesenchymal transition (EMT). However, there was no significant difference in the IHC results of the expression patterns of vimentin (VT) and cytokeratin (CK) between MPOBA-treated and control CMC cells. In conclusion, the results of the present study suggested that MPOBA exhibited significant anticancer activity by inducing apoptosis in both CMCs via upregulation of TP53 and BAX and downregulation of BCL-2 relative mRNA expression. MPOBA may prove to be a potential candidate drug to be further investigated as a therapeutic agent for CMC.

RESUMEN

We report 3 cases of patients with a history of extra-mammary cancer who presented with breast nodules, leading to diagnostic challenges and occasional misleading imaging findings. These cases highlight the significance of radiologists considering breast metastases as a potential component of the differential diagnosis when assessing patients with a history of cancer who exhibit palpable breast nodules. Furthermore, these cases underscore the importance of integrating various imaging techniques with histological and immunohistochemical analyses of the lesions to achieve precise diagnoses, ultimately ensuring the highest quality of care for these patients.

RESUMEN

INTRODUCTION: Animal models play a crucial role in breast cancer research, in particular mice and rats, who develop mammary tumors that closely resemble their human counterparts. These models allow the study of mechanisms behind breast carcinogenesis, as well as the efficacy and safety of new, and potentially more effective and advantageous therapeutic approaches. Understanding the advantages and disadvantages of each model is crucial to select the most appropriate one for the research purpose. AREA COVERED: This review provides a concise overview of the animal models available for breast cancer research, discussing the advantages and disadvantages of each one for searching new and more effective approaches to treatments for this type of cancer. EXPERT OPINION: Rodent models provide valuable information on the genetic alterations of the disease, the tumor microenvironment, and allow the evaluation of the efficacy of chemotherapeutic agents. However, in vivo models have limitations, and one of them is the fact that they do not fully mimic human diseases. Choosing the most suitable model for the study purpose is crucial for the development of new therapeutic agents that provide better care for breast cancer patients.

Asunto(s)

Neoplasias de la Mama , Ratones , Ratas , Humanos , Animales , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Modelos Animales de Enfermedad , Desarrollo de Medicamentos , Microambiente Tumoral

RESUMEN

Treatment modalities for breast cancer, including cyclophosphamide chemotherapy, have been associated with the development of cognitive decline (CRCD), which is characterized by impairments in memory, concentration, attention, and executive functions. We and others have identified a link between inflammation and decreased cognitive performance in patients with breast cancer receiving chemotherapy. In order to better understand the inflammation-associated molecular changes within the brain related to tumor alone or in combination with chemotherapy, we orthotopically implanted mouse mammary tumors (E0771) into female C57BL/6 mice and administered clinically relevant doses of cyclophosphamide and doxorubicin intravenously at weekly intervals for four weeks. We measured serum cytokines and markers of neuroinflammation at 48 h and up to one month post-treatment and tested memory using a reward-based delayed spatial alternation paradigm. We found that breast tumors and chemotherapy altered systemic inflammation and neuroinflammation. We further found that the presence of tumor and chemotherapy led to a decline in memory over time at the longest delay, when memory was the most taxed, compared to shorter delay times. These findings in a clinically relevant mouse model shed light on possible biomarkers for CRCD and add to the growing evidence that anti-inflammatory strategies have the potential to mitigate cancer- or treatment-related side effects.

RESUMEN

Mammary cancer is the most frequently diagnosed neoplasia in women and non-spayed female dogs and is one of the leading causes of death in both species. Canines develop spontaneous mammary tumors that share a significant number of biological, clinical, pathological and molecular characteristics with human breast cancers. This review provides a detailed description of the histological, molecular and clinical aspects of mammary cancer in canines; it discusses risk factors and currently available diagnostic and treatment options, as well as remaining challenges and unanswered questions. The incidence of mammary tumors is highly variable and is impacted by biological, pathological, cultural and socioeconomic factors, including hormonal status, breed, advanced age, obesity and diet. Diagnosis is mainly based on histopathology, although several efforts have been made to establish a molecular classification of canine mammary tumors to widen the spectrum of treatment options, which today rely heavily on surgical removal of tumors. Lastly, standardization of clinical study protocols, development of canine-specific biological tools, establishment of adequate dog-specific disease biomarkers and identification of targets for the development of new therapies that could improve survival and have less adverse effects than chemotherapy are among the remaining challenges.

RESUMEN

Canine inflammatory mammary cancer (IMC) is a highly aggressive and lethal cancer in dogs serving as a valuable animal model for its human counterpart, inflammatory breast cancer (IBC), both lacking effective therapies. Intratumoral immunotherapy (IT-IT) with empty cowpea mosaic virus (eCPMV) nanoparticles has shown promising results, demonstrating a reduction in tumor size, longer survival rates, and improved quality of life. This study compares the transcriptomic profiles of tumor samples from female dogs with IMC receiving eCPMV IT-IT and medical therapy (MT) versus MT alone. Transcriptomic analyses, gene expression profiles, signaling pathways, and cell type profiling of immune cell populations in samples from four eCPMV-treated dogs with IMC and four dogs with IMC treated with MT were evaluated using NanoString Technologies using a canine immune-oncology panel. Comparative analyses revealed 34 differentially expressed genes between treated and untreated samples. Five genes (CXCL8, S100A9, CCL20, IL6, and PTGS2) involved in neutrophil recruitment and activation were upregulated in the treated samples, linked to the IL17-signaling pathway. Cell type profiling showed a significant increase in neutrophil populations in the tumor microenvironment after eCPMV treatment. These findings highlight the role of neutrophils in the anti-tumor response mediated by eCPMV IT-IT and suggest eCPMV as a novel therapeutic approach for IBC/IMC.

Asunto(s)

Comovirus , Neoplasias Inflamatorias de la Mama , Humanos , Perros , Animales , Femenino , Transcriptoma , Neutrófilos , Calidad de Vida , Perfilación de la Expresión Génica , Microambiente Tumoral

RESUMEN

The lack of optimal models to evaluate novel agents is delaying the development of effective immunotherapies against human breast cancer (BC). In this prospective open label study, we applied neoadjuvant intratumoral immunotherapy with empty cowpea mosaic virus-like particles (eCPMV) to 11 companion dogs diagnosed with canine mammary cancer (CMC), a spontaneous tumor resembling human BC. We found that two neoadjuvant intratumoral eCPMV injections resulted in tumor reduction in injected tumors in all patients and in noninjected tumors located in the ipsilateral and contralateral mammary chains of injected dogs. Tumor reduction was independent of clinical stage, tumor size, histopathologic grade, and tumor molecular subtype. RNA-seq-based analysis of injected tumors indicated a decrease in DNA replication activity and an increase in activated dendritic cell infiltration in the tumor microenvironment. Immunohistochemistry analysis demonstrated significant intratumoral increases in neutrophils, T and B lymphocytes, and plasma cells. eCPMV intratumoral immunotherapy demonstrated antitumor efficacy without any adverse effects. This novel immunotherapy has the potential for improving outcomes for human BC patients.

Asunto(s)

Neoplasias de la Mama , Comovirus , Humanos , Animales , Perros , Femenino , Terapia Neoadyuvante , Estudios Prospectivos , Neoplasias de la Mama/terapia , Inmunoterapia , Microambiente Tumoral

RESUMEN

Obesity has been identified as a serious health concern in domestic cats. Feline mammary cancer (FMC) is also a concern, as it is highly prevalent and aggressive. Considering the identified connection between obesity and breast cancer, it is worthwhile to investigate the potential obesity-cancer relationship in FMC. This review investigated the association between adipokines and other obesity-associated molecules and FMC, with the aim of identifying gaps in the current literature for future research. Based on the reports to date, it was found that tissue concentrations of leptin, serum concentrations of leptin receptor, serum amyloid A, and estrogen correlate positively with FMC, and serum concentrations of leptin correlate negatively with FMC. The roles of adiponectin and prolactin in FMC development were also investigated, but the reports are either lacking or insufficient to suggest an association. Numerous research gaps were identified and could be used as opportunities for future research. These include the need for studies on additional cohorts to confirm the association of leptin/leptin receptor and serum amyloid A with FMC, and to address the role of adiponectin and prolactin in FMC. It is also important to investigate the genetic determinants of FMC, evaluate the use of molecular-targeted therapies in FMC, and exploit the enrichment of the triple-negative immunophenotype in FMC to address current clinical needs for both human triple-negative breast cancer and FMC. Finally, mechanistic studies with any of the molecules reviewed are scarce and are important to generate hypotheses and ultimately advance our knowledge and the outcome of FMC.