RESUMO
ACBD3 overexpression has previously been found to correlate with worse prognosis for breast cancer patients and, as an incredibly diverse protein in both function and cellular localisation, ACBD3 may have a larger role in breast cancer than previously thought. This study further investigated ACBD3's role in breast cancer. Bioinformatic databases were queried to characterise ACBD3 expression and mutation in breast cancer and to investigate how overexpression affects breast cancer patient outcomes. Immunohistochemistry was carried out to examine ACBD3 location within cells and tissue structures. ACBD3 was more highly expressed in breast cancer than in any other cancer or matched normal tissue, and expression over the median level resulted in reduced relapse-free, overall, and distant metastasis-free survival for breast cancer patients as a whole, with some differences observed between subtypes. IHC analysis found that ACBD3 levels varied based on hormone receptor status, indicating that ACBD3 could be a candidate biomarker for poor patient prognosis in breast cancer and may possibly be a biomarker for ER signal reprogramming of precancerous breast tissue.
Assuntos
Neoplasias da Mama , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/genética , Neoplasias da Mama/metabolismo , Biologia Computacional , Feminino , Humanos , Proteínas de Membrana/metabolismo , Recidiva Local de NeoplasiaAssuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Recidiva Local de Neoplasia , Humanos , Feminino , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Recidiva Local de Neoplasia/mortalidade , Carcinoma Intraductal não Infiltrante/mortalidade , Carcinoma Intraductal não Infiltrante/terapia , Carcinoma Intraductal não Infiltrante/patologiaAssuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Axila , Neoplasias da Mama/patologia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Biópsia de Linfonodo Sentinela , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/radioterapia , Neoplasias de Mama Triplo Negativas/cirurgiaRESUMO
BACKGROUND: Clinicians use clinical and pathological parameters, such as tumour size, grade and nodal status, to make decisions on adjuvant treatments for breast cancer. However, therapeutic decisions based on these features tend to vary due to their subjectivity. Computational and mathematical algorithms were developed using clinical outcome data from breast cancer registries, such as Adjuvant! Online and NHS PREDICT. More recently, assessments of molecular profiles have been applied in the development of better prognostic tools. METHODS: Based on the available literature on online registry-based tools and genomic assays, we evaluated whether these online tools could be valid and accurate alternatives to genomic and molecular profiling of the individual breast tumour in aiding therapeutic decisions, particularly in patients with early ER-positive breast cancer. RESULTS AND CONCLUSIONS: Early breast cancer is currently considered a systemic disease and a complex ecosystem with behaviour determined by the complex genetic and molecular signatures of the tumour cells, mammary stem cells, microenvironment and host immune system. We anticipate that molecular profiling will continue to evolve, expanding beyond the primary tumour to include the tumour microenvironment, cancer stem cells and host immune system. This should further refine therapeutic decisions and optimise clinical outcome. This article was specially invited by the editors and represents work by leading researchers.
Assuntos
Neoplasias da Mama/diagnóstico , Perfilação da Expressão Gênica/métodos , Software , Neoplasias da Mama/genética , Feminino , Genômica/métodos , Humanos , Sistemas On-Line , PrognósticoAssuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/epidemiologia , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Mastectomia , Mastectomia Segmentar , Recidiva Local de Neoplasia/epidemiologiaRESUMO
BACKGROUND: Data from providers of private cancer care are not yet formally included in English cancer registration data. This study aimed to test the exchange of breast cancer data from one Hospital Corporation of America International (HCAI) hospital in London with the cancer registration system and assess the suitability of these data for comparative analyses of case mix and adjusted survival. METHODS: Data on 199 London women receiving 'only HCAI care', 278 women receiving 'some HCAI care' (HCAI and other services), and 31,234 other London women diagnosed between 2005 and 2011 could be identified and compared. Overall survival was estimated using the Kaplan-Meier method, and Cox regression was used to adjust for age, socioeconomic deprivation, year of diagnosis, stage of disease and recorded treatment. RESULTS: Women receiving 'only HCAI care' were younger, lived in areas of higher affluence (47.8 % vs 27.6 %) and appeared less likely to be recorded as having screen-detected (2.5 % vs 25.0 %) disease than other London women. Women receiving 'some HCAI care' were more similar to 'HCAI only' women. Although HCAI stage of disease data completeness improved during the study period, this was less complete overall than cancer registration data and limited the comparative survival analyses. An apparent survival advantage for 'HCAI only' women compared with other London women (hazard ratio 0.48, 95 % confidence interval (CI): 0.32-0.74) was attenuated and no longer statistically significant after adjustment (0.79, 95 % CI: 0.51-1.21). Women receiving 'some HCAI care' appeared to have higher survival (hazard ratio 0.24, 95 % CI 0.14-0.41) which was attenuated to 0.48 (95 % CI: 0.28-0.80) in the fully adjusted model. CONCLUSIONS: Exchange of data between the private cancer sector and the English cancer registration service can identify patients who receive all or some private care. The better survival of women receiving only or some HCAI breast cancer care appears to be at least partly explained by demographic, disease, and treatment factors. However, larger studies using similarly quality assured datasets and more complete staging data from the private sector are needed to produce definitive comparative results.
Assuntos
Neoplasias da Mama/mortalidade , Idoso , Idoso de 80 Anos ou mais , Grupos Diagnósticos Relacionados , Feminino , Hospitais Privados , Humanos , Londres , Pessoa de Meia-Idade , Projetos Piloto , Modelos de Riscos Proporcionais , Sistema de Registros , Análise de Regressão , Análise de SobrevidaAssuntos
Neoplasias da Mama , Mama , Detecção Precoce de Câncer , Humanos , Mamografia , Reino UnidoRESUMO
Death-associated protein 3 (DAP3) is a molecule with a significant role in the control of both apoptosis and anoikis. Apoptosis is the predominant type of programmed cell death (PCD) which may occur in response to irreparable damage to DNA, or in response to induction by inflammatory cells. Anoikis is subset of apoptosis which occurs in epithelial cells in response to detachment from the surrounding matrix. Both apoptosis and anoikis are of interest in the context of carcinogenesis. In this review, we shall discuss apoptosis and anoikis, and the recent literature regarding the role of DAP3 in both these pathways.
RESUMO
Breast cancer stands as the most frequently diagnosed malignancy in women, holding a prominent position among the leading causes of cancer-related fatalities on a global scale. Despite significant advances in treatment modalities, approximately 20% of patients experience relapses after the first 5 years of postdiagnosis surveillance. While initial investigations from the 1970s indicated comparable survival rates between breast-conserving surgery (BCS) coupled with radiation therapy and mastectomy, recent research suggests that, within the context of modern systemic and radiation therapy, BCS followed by radiation may offer an improved overall survival benefit. Nevertheless, extended follow-up studies have unveiled a notable increase in the risk of locoregional recurrence associated with breast conserving therapy in contrast to mastectomy. This article introduces a novel hypothesis rooted in the biological phenomenon of homing to elucidate this intriguing clinical observation. We postulate that a breast homing mechanism of reactivated circulating and disseminated tumor cells mediated by chemotaxis involving at least the CXCR4-SDF-1 axis may provide a biological rationale for this clinical phenomenon.
Assuntos
Neoplasias da Mama , Mastectomia , Feminino , Humanos , Mastectomia Segmentar , Neoplasias da Mama/patologia , Recidiva Local de Neoplasia/patologia , SeguimentosRESUMO
This article explores the intricate relationship between airborne particulate matter (PM), specifically PM2.5, and its profound impact on human health, emphasising the heightened risks of cancer. Examining the composition and characteristics of PM2.5, such as particle size and surface area, reveals its ability to induce inflammatory injury and oxidative damage. The carcinogenic potential extends beyond respiratory implications, affecting various organs, including the digestive tract, breast, and prostate. In addition to the genotoxic effects of PM2.5, attached polycyclic aromatic hydrocarbons are recognized to be endocrine-disrupting chemicals with specific implications for breast and prostate cancer. Long-term exposure to PM2.5 is associated with increased cancer mortality, with specific risks identified for different cancer types. The linear correlation between cancer risk and PM2.5 concentration calls for a re-evaluation of permissible emission levels. The article concludes by proposing specific mitigating strategies for individuals exposed to elevated PM2.5. It suggests antioxidant-rich diets and supplements, and exploring inhalation-based antioxidant administration as potential protective measures.
Assuntos
Poluentes Atmosféricos , Neoplasias , Hidrocarbonetos Policíclicos Aromáticos , Masculino , Humanos , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/química , Poluentes Atmosféricos/toxicidade , Antioxidantes , Material Particulado/análise , Material Particulado/toxicidade , Tamanho da Partícula , Neoplasias/etiologia , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Monitoramento AmbientalRESUMO
This perspective focuses on axillary soft tissue (AXT) involvement in breast cancer, revealing diverse pathological entities beyond traditional axillary lymph node metastasis. AXT involvement is linked to increased risks of distant metastasis and locoregional failure, emphasizing its significance in predicting breast cancer outcomes. We posit that AXT involvement could signify a retrograde metastatic event stemming from reactivated circulating tumor cells navigating towards the axillary soft tissue guided by chemokines. Therefore, AXT disease warrants aggressive systemic therapy. Axillary radiation therapy could be a potentially preferable alternative to axillary lymph node dissection. Routine reporting of axillary soft tissue involvement is crucial for accurate treatment planning.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Linfonodos/patologia , Excisão de Linfonodo , Metástase Linfática/patologia , Axila/patologiaRESUMO
Breast cancer, a multifaceted disease, presents a dynamic ecosystem where the primary tumor interacts intricately with its microenvironment, circulatory system, and distant organs. Circulating tumor cells (CTCs) disseminate from the primary tumor to organs, such as the brain, lungs, liver, and bones, encountering various fates: cell death, cellular dormancy, or senescence. Dormant cells, characterized by reversible growth arrest at the G0/G1 phase of the cell cycle, pose a significant challenge as they evade conventional treatments and can later reawaken, leading to cancer relapse. The phenomenon of tumor dormancy is influenced by the tumor microenvironment, immune modulation, and cellular adaptations. Emerging evidence suggests that breast-conserving surgery coupled with radiation therapy offers superior survival benefits compared to mastectomy, potentially due to the 'breast homing phenomenon.' This hypothesis posits that residual breast tissue provides a niche for reactivated dormant cells, reducing distant metastasis. Immunotherapy and lifestyle modifications, including diet and exercise, show promise in managing dormant cells. Understanding the mechanisms of dormancy and developing targeted therapies are crucial for achieving long-term remission and potentially curing breast cancer.
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Neoplasias da Mama , Microambiente Tumoral , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Neoplasias da Mama/metabolismo , Feminino , Células Neoplásicas Circulantes/patologia , Células Neoplásicas Circulantes/metabolismoRESUMO
Breast cancer remains a global health challenge, prompting a search for preventive strategies beyond conventional approaches. This review explores the potential of specific micronutrients, including antioxidants, vitamins, and probiotics, in breast cancer prevention. Through an extensive literature search encompassing PubMed up to March 2024, 14 micronutrients emerged with promising roles in breast cancer prevention. These include five vitamins: folate, vitamin D, vitamin B6, beta carotene, and vitamin C and nine other micronutrients: curcumin, piperine, epigallocatechin-3-gallate, quercetin, sulforaphane, indole-3-carbinol, lactobacillus, n-3 polyunsaturated fatty acids and lycopene. Understanding the efficacy of these micronutrients could pave the way for personalized preventive interventions, offering new avenues for reducing breast cancer incidence and improving public health outcomes.