A high-cholesterol diet promotes the intravasation of breast tumor cells through an LDL-LDLR axis.

Most metastases in breast cancer occur via the dissemination of tumor cells through the bloodstream. How tumor cells enter the blood (intravasation) is, however, a poorly understood mechanism at the cellular and molecular levels. Particularly uncharacterized is how intravasation is affected by systemic nutrients. High levels of systemic LDL-cholesterol have been shown to contribute to breast cancer progression and metastasis in various models, but the cellular and molecular mechanisms involved are still undisclosed. Here we show that a high- cholesterol diet promotes intravasation in two mouse models of breast cancer and that this could be reverted by blocking LDL binding to LDLR in tumor cells. Moreover, we show that LDL promotes vascular invasion in vitro and the intercalation of tumor cells with endothelial cells, a phenotypic change resembling vascular mimicry (VM). At the molecular level, LDL increases the expression of SERPINE2, previously shown to be required for both VM and intravasation. Overall, our manuscript unravels novel mechanisms by which systemic hypercholesterolemia may affect the onset of metastatic breast cancer by favouring phenotypic changes in breast cancer cells and increasing intravasation.

Compatibility of Entomopathogenic Nematodes with Chemical Insecticides for the Control of Drosophila suzukii (Diptera: Drosophilidae).

The spotted-wing drosophila, Drosophila suzukii (Matsumura) (Diptera: Drosophilidae), is a pest that reduces the productivity of small fruits. Entomopathogenic nematodes (EPNs) and chemical insecticides can suppress this pest, but the compatibility of the two approaches together requires further examination. This laboratory study evaluated the compatibility of Steinernema brazilense IBCBn 06, S. carpocapsae IBCBn 02, Heterorhabditis amazonensis IBCBn 24, and H. bacteriophora HB with ten chemical insecticides registered for managing D. suzukii pupae. In the first study, most insecticides at the recommended rate did not reduce the viability (% of living infective juveniles (IJs)) of S. braziliense and both Heterorhabditis species. The viability of S. carpocapsae was lowered by exposure to spinetoram, malathion, abamectin, azadirachtin, deltamethrin, lambda-cyhalothrin, malathion, and spinetoram after 48 h. During infectivity bioassays, phosmet was compatible with all the EPNs, causing minimal changes in infectivity (% pupal mortality) and efficiency relative to EPN-only controls, whereas lambda-cyhalothrin generally reduced infectivity of EPNs on D. suzukii pupae the most, with a 53, 75, 57, and 13% reduction in infectivity efficiency among H. bacteriophora, H. amazonensis, S. carpocapsae, and S. brazilense, respectively. The second study compared pupal mortality caused by the two most compatible nematode species and five insecticides in various combinations. Both Heterorhabditis species caused 78-79% mortality among D. suzukii pupae when used alone, and were tested in combination with spinetoram, malathion, azadirachtin, phosmet, or novaluron at a one-quarter rate. Notably, H. bacteriophora caused 79% mortality on D. suzukii pupae when used alone, and 89% mortality when combined with spinetoram, showing an additive effect. Novaluron drastically reduced the number of progeny IJs when combined with H. amazonensis by 270 IJs and H. bacteriophora by 218. Any adult flies that emerged from EPN-insecticide-treated pupae had a shorter lifespan than from untreated pupae. The combined use of Heterorhabditis and compatible chemical insecticides was promising, except for novaluron.

Pathogenicity and Virulence of Different Concentrations of Brazilian Isolates of Entomopathogenic Nematodes Against Drosophila suzukii.

The invasive pest Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) was recently recorded in Brazil and constitutes a threat to fruit growing, mainly for small, soft fruits. Recent advances in research on ways of controlling D. suzukii involve the use of entomopathogenic nematodes (EPNs). In this context, the objective of this study was to evaluate the pathogenicity and virulence of four isolates in different concentrations against D. suzukii pupae. The EPN isolates used in trials were Steinernema brazilense IBCBn 06, S. carpocapsae IBCBn 02, Heterorhabditis bacteriophora HB, and H. amazonensis IBCBn 24. Both H. amazonensis IBCBn 24 and H. bacteriophora HB were effective in controlling D. suzukii as they caused a mortality rate of 86.25% and 80.0%, and virulence of 549.75 IJs/pupae and 787.75 IJs/pupae in the concentrations of 1800 IJs/ml and 5400 IJs/ml, respectively. The lowest lethal concentrations (LC50) of juveniles were found in host pupae with 771.63 IJs/ml of H. bacteriophora HB and 1115.49 IJs/ml of H. amazonensis IBCBn 24. Results showed that both EPNs, H. amazonensis IBCBn 24 and H. bacteriophora HB, could be promising eco-friendly biological agents to control D. suzukii.

Mitochondrial Metabolism Drives Low-density Lipoprotein-induced Breast Cancer Cell Migration.

Most cancer-related deaths are due to metastases. Systemic factors, such as lipid-enriched environments [as low-density lipoprotein (LDL)-cholesterol], favor breast cancer, including triple-negative breast cancer (TNBC) metastasis formation. Mitochondria metabolism impacts TNBC invasive behavior but its involvement in a lipid-enriched setting is undisclosed. Here we show that LDL increases lipid droplets, induces CD36 and augments TNBC cells migration and invasion in vivo and in vitro. LDL induces higher mitochondrial mass and network spread in migrating cells, in an actin remodeling-dependent manner, and transcriptomic and energetic analyses revealed that LDL renders TNBC cells dependent on fatty acids (FA) usage for mitochondrial respiration. Indeed, engagement on FA transport into the mitochondria is required for LDL-induced migration and mitochondrial remodeling. Mechanistically, LDL treatment leads to mitochondrial long-chain fatty acid accumulation and increased reactive oxygen species (ROS) production. Importantly, CD36 or ROS blockade abolished LDL-induced cell migration and mitochondria metabolic adaptations. Our data suggest that LDL induces TNBC cells migration by reprogramming mitochondrial metabolism, revealing a new vulnerability in metastatic breast cancer. Significance: LDL induces breast cancer cell migration that relies on CD36 for mitochondrial metabolism and network remodeling, providing an antimetastatic metabolic strategy.

Use of scanning electron microscope to evaluate the marginal fit of protocol bars obtained through benchtop or intraoral digital scanners

Aim: To evaluate the marginal fit of protocol bars milled from digital models obtained by conventional molding followed by bench scanning or digital molding with an intraoral scanner. Methods: Four morse-cone implants and the mini-pillars were installed in a 3D printed mandible model (master model). Digital models of the master model were obtained by (n=10): (Group A - Conventional) conventional (analog) molding of the master model followed by bench scanning or (Group B - Digital) molding of the master model with an intraoral scanner. All-on-four protocol bars were designed and milled from the digital models for both groups and screwed into the master model. Scanning electron microscopy (SEM) images from the distal, central, and mesial regions of each implant were obtained and the implant-protocol bar marginal fit was measured in an image software (Image J). The mean misfit of each region was analyzed by two-factor ANOVA, Tukey test, and Student's t-test (0,05 = 0.05). Results: The digital approach (B) showed higher misadaptation than the conventional approach (A, p < 0.05), regardless of the region evaluated. In group A, the central region showed higher maladjustment than the mesial region (p<0.05), however, there were no differences among regions of group B (p>0.05). Conclusion: The conventional method of acquiring digital models using the bench scanner produced bars for the All-On-Four protocol with better marginal fit than the digital models obtained with an intraoral scanner

On the Relevance of Soft Tissue Sarcomas Metabolic Landscape Mapping.

Soft tissue sarcomas (STS) prognosis is disappointing, with current treatment strategies being based on a "fit for all" principle and not taking distinct sarcoma subtypes specificities and genetic/metabolic differences into consideration. The paucity of precision therapies in STS reflects the shortage of studies that seek to decipher the sarcomagenesis mechanisms. There is an urge to improve STS diagnosis precision, refine STS classification criteria, and increase the capability of identifying STS prognostic biomarkers. Single-omics and multi-omics studies may play a key role on decodifying sarcomagenesis. Metabolomics provides a singular insight, either as a single-omics approach or as part of a multi-omics strategy, into the metabolic adaptations that support sarcomagenesis. Although STS metabolome is scarcely characterized, untargeted and targeted metabolomics approaches employing different data acquisition methods such as mass spectrometry (MS), MS imaging, and nuclear magnetic resonance (NMR) spectroscopy provided important information, warranting further studies. New chromatographic, MS, NMR-based, and flow cytometry-based methods will offer opportunities to therapeutically target metabolic pathways and to monitorize the response to such metabolic targeting therapies. Here we provide a comprehensive review of STS omics applications, comprising a detailed analysis of studies focused on the metabolic landscape of these tumors.

Sarcoma Metabolomics: Current Horizons and Future Perspectives.

The vast array of metabolic adaptations that cancer cells are capable of assuming, not only support their biosynthetic activity, but also fulfill their bioenergetic demands and keep their intracellular reduction-oxidation (redox) balance. Spotlight has recently been placed on the energy metabolism reprogramming strategies employed by cancer cells to proliferate. Knowledge regarding soft tissue and bone sarcomas metabolome is relatively sparse. Further characterization of sarcoma metabolic landscape may pave the way for diagnostic refinement and new therapeutic target identification, with benefit to sarcoma patients. This review covers the state-of-the-art knowledge on cancer metabolomics and explores in detail the most recent evidence on soft tissue and bone sarcoma metabolomics.

Effectiveness of Entomopathogenic Nematodes Against Ceratitis capitata (Diptera: Tephritidae) Pupae and Nematode Compatibility with Chemical Insecticides.

The Mediterranean fruit fly Ceratitis capitata (Wiedemann, 1824) (Diptera: Tephritidae) is among the main pests of fruit crops worldwide. Biological control using entomopathogenic nematodes (EPNs) may be an alternative to suppress populations of this pest. Thus, the aim of this study was to evaluate the pathogenicity and virulence of six EPN isolates (Heterorhabditis bacteriophora HB, H. amazonensis IBCB-n24, Steinernema carpocapsae IBCB-n02, S. rarum PAM-25, S. glaseri IBCB-n47, and S. brazilense IBCB-n06) against C. capitata pupae. The compatibility of EPNs with different chemical insecticides that are registered for management of C. capitata was also assessed. Isolates of H. bacteriophora HB and S. brazilense IBCB-n06 at a concentration of 1,000 infective juveniles (IJ)/ml proved to be most pathogenic to C. capitata (70 and 80% mortality, respectively). In contrast, the isolates H. amazonensis IBCB-n24, Steinernema carpocapsae IBCB-n02, S. rarum PAM-25, S. glaseri IBCB-n47 provided pupal mortality of less than 60%. Bioassays to determine lethal concentrations indicated that concentrations of 600 IJ/ml (H. bacteriophora HB) and 1,000 IJ/ml (S. brazilense IBCB-n06) showed the highest virulence against C. capitata pupae. In contrast, the highest numbers of IJs emerged at concentrations of 1,200 and 200 IJ/ml. In compatibility bioassays, malathion, spinetoram, phosmet, acetamiprid, and novaluron were considered compatible with and harmless (Class 1) to H. bacteriophora HB and S. brazilense IBCB-n06, according to IOBC/WPRS. This information is important for implementing integrated management programs for C. capitata, using biological control with EPNs, whether alone or in combination with chemical insecticides.

Satisfação e engagement: (Re)pensar a saúde e o bem-estar dos enfermeiros / Satisfaction and engagement: (Re)thinking about the health and well-being of nurses / Satisfacción y engagement: (Re)pensar la salud y el bienestar de los enfermeros

CONTEXTO: A satisfação profissional e o engagement assumem relevância na qualidade e segurança das pessoas cuidadas e na saúde mental e bem-estar dos enfermeiros. OBJETIVOS: Avaliar a satisfação profissional e o engagement dos enfermeiros; identificar variáveis profissionais preditoras da satisfação profissional e do engagement, enquanto fatores promotores da saúde e bem-estar dos enfermeiros. MÉTODOS: Estudo observacional, quantitativo, descritivo e transversal. Amostra probabilís-tica estratificada por sexo, hospital e serviço composta por 234 enfermeiros do Centro Hospitalar do Alto Minho, 204 do Hospital Santa Luzia e 30 do Hospital Conde Bertiandos, com respetivamente 171 e 24 mulheres. Utilizou-se a Escala de Satisfação dos Enfermeiros no Trabalho e a Utrecht Work Engagement Scale. RESULTADOS: Maioritariamente do sexo feminino, com média de idades ± Desvio Padrão de 42,89 ± 8,30 anos e insatisfeitos (2,83 ± 0,577). Enfermeiros com horário fixo (t=3,038; p=0,003) e exercendo especialidade (t=2,014; p=0,048) registaram médias de satisfação superiores. Enfermeiros mais experientes manifestaram-se mais satisfeitos na ‘Satisfação com a Organização e Recursos' (t=-2,006; p=0,046) e ‘Satisfação com as Dotações' (t=-2,192; p=0,029). No Hospital Conde Bertiandos a ‘Satisfação com as Dotações' foi mais baixa (t=2,182; p=0,030). Revelaram níveis de engagement moderados (4,01 ± 1,027). Enfermeiros com horário fixo (t=2,097; p=0,037) apresentaram maior engagement. CONCLUSÕES: A baixa satisfação profissional, o engagement moderado e os preditores comuns, conformam desafios e práticas inovadoras da gestão das organizações de saúde, designadamente otimização das condições psicossociais em contexto de trabalho potenciadoras da emergência do capital humano.

BACKGROUND: Job satisfaction and engagement are important in the quality and safety of caregivers and in the mental health and well-being of nurses. AIM: Evaluate the job satisfaction and engagement of nurses; identify professional variables that predict job satisfaction and engagement as factors that promote health and well-being of nurses. METHODS:Observational, quantitative, descriptive and cross-sectional study. Probabilistic sample stratified by sex, hospital and service, consisting of 234 nurses from Alto Minho Hospital Center, 204 from Santa Luzia Hospital and 30 from Conde Bertiandos Hospital, with 171 and 24 women, respectively. The Nurses' Satisfaction at Work Scale and the Utrecht Work Engagement Scale were used. RESULTS:Mostly female, with mean ages ± standard deviation of 42.89 ± 8.30 years and dissatisfied (2.83 ± 0.577). Nurses with fixed shift schedule (t=3.038; p= 0.003) and practicing specialty (t= 2.014; p=0.048) recorded higher satisfaction averages. More experienced nurses were more satisfied with 'Satisfaction with Organization and Resources' (t=-2.006; p=0.046) and 'Satisfaction with Appropriations' (t =-2.192; p=0.029). At Conde Bertiandos Hospital 'Satisfaction with Appropriations' was lower (t=2.182; p=0.030). They revealed moderate levels of engagement (4.01 ± 1.027). Nurses with fixed shift schedule (t=2.097; p=0.037) had greater engagement. CONCLUSIONS:Low job satisfaction, moderate engagement and common predictors, shape challenges and innovative practices in the management of health organizations, namely optimization of psychosocial conditions in a work context that enhances the emergence of human capital.

CONTEXTO: La satisfacción laboral y el compromiso son importantes para la calidad y seguridad de los cuidadores y para la salud mental y el bienestar de las enfermeras. OBJETIVOS: Evaluar la satisfacción profesional y el compromiso laboral de las enfermeras; identificar las variables profesionales que predicen la satisfacción y el compromiso profesional como factores que promueven la salud y el bienestar de las enfermeras. METODOLOGÍA: Estudio observacional, cuantitativo, descriptivo y transversal. Muestra probabilística estratificada por sexo, hospital y servicio, compuesta por 234 enfermeras del Centro Hospitalario Alto Minho, 204 del Hospital Santa Luzia y 30 del Hospital Conde Bertiandos, con 171 y 24 mujeres, respectivamente. Se utilizaron la Escala de Satisfacción en el Trabajo de las Enfermeras y la Utrecht Work Engagement Scale. RESULTADOS: En su mayoría mujeres, con edades medias ± desviación estándar de 42.89 ± 8.30 años e insatisfechas (2.83 ± 0.577). Las enfermeras con horario fijo de turnos (t=3.038; p=0.003) y la práctica especializada (t=2.014; p=0.048) registraron promedios de satisfacción más altos. Las enfermeras más experimentadas estaban más satisfechas con la "Satisfacción con la Organización y los Recursos" (t=-2.006; p=0.046) y la "Satisfacción con las Apropiaciones" (t=-2.192; p=0.029). En el Hospital Conde Bertiandos, la "Satisfacción con las Apropiaciones" fue menor (t=2.182; p=0.030). Revelaron niveles moderados de compromiso laboral (4.01 ± 1.027). Las enfermeras con horario fijo de turnos (t=2.097; p=0.037) tuvieron un mayor compromiso laboral. CONCLUSIONES: La baja satisfacción profesional, lo compromiso laboral moderado y los factores predictivos comunes configuran los desafíos y las prácticas innovadoras en la gestión de las organizaciones de salud, como la optimización de las condiciones psicosociales en un contexto de trabajo que mejora el surgimiento del capital humano.

Modulating the Metabolic Phenotype of Cancer Microenvironment.

This chapter provides a brief overview of the methods to study and modulate the metabolic phenotype of the tumor microenvironment, including own research work to demonstrate the impact that metabolic shifts in the host have on cancer. Firstly, we briefly discuss the relevance of using animal models to address this topic, and also the importance of acknowledging that animals have diverse metabolic phenotypes according to species, and even with strain, age or sex. We also present original data to highlight the impact that changes in metabolic phenotype of the microenvironment have on tumor progression. Using an acute leukemia mouse xenograft model and high-fat diet we show that a shift in the host metabolic phenotype, induced by high-fat feeding, significantly impacts on tumor progression. The mechanism through which this occurs involves a direct effect of the increased levels of circulating lipoproteins in both tumor and non-neoplastic cells.

CavBench: A benchmark for protein cavity detection methods.

Extensive research has been applied to discover new techniques and methods to model protein-ligand interactions. In particular, considerable efforts focused on identifying candidate binding sites, which quite often are active sites that correspond to protein pockets or cavities. Thus, these cavities play an important role in molecular docking. However, there is no established benchmark to assess the accuracy of new cavity detection methods. In practice, each new technique is evaluated using a small set of proteins with known binding sites as ground-truth. However, studies supported by large datasets of known cavities and/or binding sites and statistical classification (i.e., false positives, false negatives, true positives, and true negatives) would yield much stronger and reliable assessments. To this end, we propose CavBench, a generic and extensible benchmark to compare different cavity detection methods relative to diverse ground truth datasets (e.g., PDBsum) using statistical classification methods.

An antisense transcript mediates MALAT1 response in human breast cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) represent a substantial portion of the human transcriptome. LncRNAs present a very stringent cell-type/tissue specificity being potential candidates for therapeutical applications during aging and disease. As example, targeting of MALAT1, a highly conserved lncRNA originally identified in metastatic non-small cell lung cancer, has shown promising results in cancer regression. Nevertheless, the regulation and specificity of MALAT1 have not been directly addressed. Interestingly, MALAT1 locus is spanned by an antisense transcript named TALAM1. METHODS: Here using a collection of breast cancer cells and in vitro and in vivo migration assays we characterized the dynamics of expression and demonstrated that TALAM1 regulates and synergizes with MALAT1 during tumorigenesis. RESULTS: Down-regulation of TALAM1 was shown to greatly impact on the capacity of breast cancer cells to migrate in vitro or to populate the lungs of immunocompromised mice. Additionally, we demonstrated that TALAM1 cooperates with MALAT1 in the regulation of the properties guiding breast cancer aggressiveness and malignancy. CONCLUSIONS: By characterizing this sense/anti-sense pair we uncovered the complexity of MALAT1 locus regulation, describing new potential candidates for cancer targeting.

Reverse torque evaluation in indexed and nonindexed abutments of Morse Taper implants in a mechanical fatigue test.

BACKGROUND: This experimental study assessed reverse torque of indexed and nonindexed (NI) abutments in Morse Taper (MT) implants in a mechanical fatigue test. MATERIALS AND METHODS: In this experimental study It was used 37 implants MT and over them installed Pilar Flex abutments (4.8 mm × 6 mm × 1.5 mm). The groups were as follows: Group A used 19 MT implants with a NI Pilar Flex abutment loaded with 32 N/cm and Group B used 18 MT implants with an indexed (IN) Pilar Flex abutment loaded with 20 N/cm. The abutments were tested according to ISO standard 14801/2007. The specimens were installed at 30° from the axial axis and underwent a 133 N load, 4 Hz frequency, and 1,000,000 cycles. Once the test was completed, the reverse torque was provided by an electronic torque meter. Data were submitted to statistical analysis using the t-test for independent samples and paired t-test. The significance level was considered P < 0.05. RESULTS: Results obtained showed that the indexed Pilar Flex abutment had a percentage of torque loss from the initial torque of 49% and the NI Pilar Flex abutment lost 14%. Paired Student's t-tests revealed that for both NI (P < 0.001) and indexed (P < 0.001) abutments, the counter torque values were significantly lower than those applied at the initial torque. CONCLUSION: According on the methodology used, the NI Pilar Flex abutment was more effective regarding the reverse torque in single-unit implant prostheses versus the indexed Pilar Flex abutment. A greater loosening in the indexed Pilar Flex abutment retaining screw was noted in the reverse torque test, and the Pilar Flex abutment failed to show good outcomes related to the cold welding effect.

Biomechanical Behavior of an Implant System Using Polyether Ether Ketone Bar: Finite Element Analysis.

AIM AND OBJECTIVES: This study assessed, through finite element analysis, the biomechanical behavior of an implant system using the All-on-Four® technique with nickel-chromium (M1) and polyether ether ketone (PEEK) bars (M2). MATERIALS AND METHODS: Implants and components were represented in three-dimensional (3D) geometric models and submitted to three types of load: axial, oblique, and load on all teeth. The 3D models were exported to a computer-aided design-like software such as Solidworks 2016 (Dassault Systemes, Solidworks Corps, USA) for editing and Nonuniform Rational Basis Splines parametrization. RESULTS: Data were analyzed according to system's areas of action: peri-implant bone, implant, intermediates, intermediates' screws, prostheses' screws, and bars. Largest peak stress was shown in M2. CONCLUSION: PEEK is a promising material for use in dentistry; however, further studies are necessary to evaluate its performance.

Meeting the needs of breast cancer: A nucleolin's perspective.

A major challenge in the management of breast cancer disease has been the development of metastases. Finding new molecular targets and the design of targeted therapeutic approaches to improve the overall survival and quality of life of these patients is, therefore, of great importance. Nucleolin, which is overexpressed in cancer cells and tumor-associated blood vessels, have been implicated in various processes supporting tumorigenesis and angiogenesis. Additionally, its overexpression has been demonstrated in a variety of human neoplasias as an unfavorable prognostic factor, associated with a high risk of relapse and low overall survival. Hence, nucleolin has emerged as a relevant target for therapeutic intervention in cancer malignancy, including breast cancer. This review focus on the contribution of nucleolin for cancer disease and on the development of therapeutic strategies targeting this protein. In this respect, it also provides a critical analysis about the potential and pitfalls of nanomedicine for cancer therapy.

Low-Density Lipoprotein Uptake Inhibits the Activation and Antitumor Functions of Human Vγ9Vδ2 T Cells.

Vγ9Vδ2 T cells, the main subset of γδ T lymphocytes in human peripheral blood, are endowed with antitumor functions such as cytotoxicity and IFNγ production. These functions are triggered upon T-cell receptor-dependent activation by non-peptidic prenyl pyrophosphates ("phosphoantigens") that are selective agonists of Vγ9Vδ2 T cells, and which have been evaluated in clinical studies. Because phosphoantigens have shown interindividual variation in Vγ9Vδ2 T-cell activities, we asked whether metabolic resources, namely lipids such as cholesterol, could affect phosphoantigen-mediated Vγ9Vδ2 T-cell activation and function. We show here that Vγ9Vδ2 T cells express the LDL receptor upon activation and take up LDL cholesterol. Resulting changes, such as decreased mitochondrial mass and reduced ATP production, correlate with downregulation of Vγ9Vδ2 T-cell activation and functionality. In particular, the expression of IFNγ, NKG2D, and DNAM-1 were reduced upon LDL cholesterol treatment of phosphoantigen-expanded Vγ9Vδ2 T cells. As a result, their capacity to target breast cancer cells was compromised both in vitro and in an in vivo xenograft mouse model. Thus, this study describes the role of LDL cholesterol as an inhibitor of the antitumor functions of phosphoantigen-activated Vγ9Vδ2 T cells. Our observations have implications for therapeutic applications dependent on Vγ9Vδ2 T cells. Cancer Immunol Res; 6(4); 448-57. ©2018 AACR.

Therapeutic Implications of the Molecular and Immune Landscape of Triple-Negative Breast Cancer.

Treatment and management of breast cancer imposes a heavy burden on public health care, and incidence rates continue to increase. Breast cancer is the most common female neoplasia and primary cause of death among women worldwide. The recognition of breast cancer as a complex and heterogeneous disease, comprising different molecular entities, was a landmark in our understanding of this malignancy. Valuing the impact of the molecular characteristics on tumor behavior enabled a better assessment of a patient's prognosis and increased the predictive power to therapeutic response and clinical outcome. Molecular heterogeneity is also prominent in the triple-negative breast cancer subtype, and is reflected by the distinct prognostic and patient's sensitivity to treatment, being chemotherapy the only systemic treatment currently available. From a therapeutic perspective, gene expression profiling of triple-negative tumors has notably contributed to the exploration of new druggable targets and brought to light the need to align these patients to the various therapies according to their triple-negative subtype. Additionally, the higher amount of tumor infiltrating lymphocytes, and the prevalence of an increased expression of PD-1 receptor and its ligand, PD-L1, in triple-negative tumors, created a new treatment opportunity with immune checkpoint inhibitors. This manuscript addresses the current knowledge on the molecular and immune profiles of breast cancer, and its impact on the development of targeted therapies, with a particular emphasis on the triple-negative subtype.