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1.
Nat Commun ; 11(1): 4642, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32934200

RESUMO

Epigenetic regulation plays an important role in governing stem cell fate and tumorigenesis. Lost expression of a key DNA demethylation enzyme TET2 is associated with human cancers and has been linked to stem cell traits in vitro; however, whether and how TET2 regulates mammary stem cell fate and mammary tumorigenesis in vivo remains to be determined. Here, using our recently established mammary specific Tet2 deletion mouse model, the data reveals that TET2 plays a pivotal role in mammary gland development and luminal lineage commitment. We show that TET2 and FOXP1 form a chromatin complex that mediates demethylation of ESR1, GATA3, and FOXA1, three key genes that are known to coordinately orchestrate mammary luminal lineage specification and endocrine response, and also are often silenced by DNA methylation in aggressive breast cancers. Furthermore, Tet2 deletion-PyMT breast cancer mouse model exhibits enhanced mammary tumor development with deficient ERα expression that confers tamoxifen resistance in vivo. As a result, this study elucidates a role for TET2 in governing luminal cell differentiation and endocrine response that underlies breast cancer resistance to anti-estrogen treatments.


Assuntos
Diferenciação Celular , Proteínas de Ligação a DNA/metabolismo , Estradiol/metabolismo , Estrogênios/metabolismo , Glândulas Mamárias Animais/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/fisiopatologia , Linhagem da Célula , Metilação de DNA , Proteínas de Ligação a DNA/genética , Sistema Endócrino/metabolismo , Epigênese Genética , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Glândulas Mamárias Animais/fisiopatologia , Camundongos , Camundongos Knockout , Proteínas Proto-Oncogênicas/genética
3.
Proc Natl Acad Sci U S A ; 117(28): 16500-16508, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32601199

RESUMO

Despite the implementation of multiple HER2-targeted therapies, patients with advanced HER2+ breast cancer ultimately develop drug resistance. Stromal fibroblasts represent an abundant cell type in the tumor microenvironment and have been linked to poor outcomes and drug resistance. Here, we show that fibroblasts counteract the cytotoxic effects of HER2 kinase-targeted therapy in a subset of HER2+ breast cancer cell lines and allow cancer cells to proliferate in the presence of the HER2 kinase inhibitor lapatinib. Fibroblasts from primary breast tumors, normal breast tissue, and lung tissue have similar protective effects on tumor cells via paracrine factors. This fibroblast-mediated reduction in drug sensitivity involves increased expression of antiapoptotic proteins and sustained activation of the PI3K/AKT/MTOR pathway, despite inhibition of the HER2 and the RAS-ERK pathways in tumor cells. HER2 therapy sensitivity is restored in the fibroblast cocultures by combination treatment with inhibitors of MTOR or the antiapoptotic proteins BCL-XL and MCL-1. Expression of activated AKT in tumor cells recapitulates the effects of fibroblasts resulting in sustained MTOR signaling and poor lapatinib response. Lapatinib sensitivity was not altered by fibroblasts in tumor cells that exhibited sustained MTOR signaling due to a strong gain-of-function PI3KCA mutation. These findings indicate that in addition to tumor cell-intrinsic mechanisms that cause constitutive PI3K/AKT/MTOR pathway activation, secreted factors from fibroblasts can maintain this pathway in the context of HER2 inhibition. Our integrated proteomic-phenotypic approach presents a strategy for the discovery of protective mechanisms in fibroblast-rich tumors and the design of rational combination therapies to restore drug sensitivity.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Fibroblastos/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias da Mama/genética , Neoplasias da Mama/fisiopatologia , Linhagem Celular Tumoral , Feminino , Fibroblastos/citologia , Fibroblastos/enzimologia , Humanos , Lapatinib/farmacologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/genética
4.
Nat Commun ; 11(1): 3606, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32681016

RESUMO

Mitochondrial metabolism has emerged as a promising target against the mechanisms of tumor growth. Herein, we have screened an FDA-approved library to identify drugs that inhibit mitochondrial respiration. The ß1-blocker nebivolol specifically hinders oxidative phosphorylation in cancer cells by concertedly inhibiting Complex I and ATP synthase activities. Complex I inhibition is mediated by interfering the phosphorylation of NDUFS7. Inhibition of the ATP synthase is exerted by the overexpression and binding of the ATPase Inhibitory Factor 1 (IF1) to the enzyme. Remarkably, nebivolol also arrests tumor angiogenesis by arresting endothelial cell proliferation. Altogether, targeting mitochondria and angiogenesis triggers a metabolic and oxidative stress crisis that restricts the growth of colon and breast carcinomas. Nebivolol holds great promise to be repurposed for the treatment of cancer patients.


Assuntos
Antagonistas Adrenérgicos/farmacologia , Indutores da Angiogênese/farmacologia , Neoplasias da Mama/fisiopatologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/fisiopatologia , Mitocôndrias/efeitos dos fármacos , Nebivolol/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Feminino , Humanos , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , ATPases Mitocondriais Próton-Translocadoras/genética , ATPases Mitocondriais Próton-Translocadoras/metabolismo , NADH Desidrogenase/genética , NADH Desidrogenase/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Proteínas/genética , Proteínas/metabolismo
5.
Arch Med Res ; 51(6): 542-547, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32507367

RESUMO

PURPOSE: In this study, we investigated the circulating levels of 25-hydroxyvitamin D (25[OH]D) in Brazilian women with breast cancer in samples collected at diagnosis, and correlated these with clinicopathological parameters relevant to disease prognosis. METHODS: This study involved 147 women diagnosed with infiltrative ductal carcinoma whose peripheral blood samples were collected, to have 25(OH)D levels measured in plasma. RESULTS: Our findings indicated that circulating 25(OH)D levels at diagnosis were insufficient in patients with breast cancer. Further, 25(OH)D reduced plasmatic levels at diagnosis correlated significantly with poor prognosis parameters, including axillar positivity, chemoresistance and metastasis. Patients bearing triple-negative tumors also presented reduced 25(OH)D in plasma when compared to those who carried Luminal tumors. Our data suggest relevant correlations when 25(OH)D is reduced in plasma at diagnosis, such as advanced disease with axillar positivity, chemoresistance with advanced disease, early age at diagnosis with high histological grade and dead with axilla positivity. CONCLUSIONS: Altogether, our findings reinforce that 25(OH)D reduction can be a plausible marker of disease prognosis in breast cancer.


Assuntos
Axila/patologia , Neoplasias da Mama/complicações , Vitamina D/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/fisiopatologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Vitamina D/sangue
6.
Nat Commun ; 11(1): 3020, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32541686

RESUMO

The subversion of endocytic routes leads to malignant transformation and has been implicated in human cancers. However, there is scarce evidence for genetic alterations of endocytic proteins as causative in high incidence human cancers. Here, we report that Epsin 3 (EPN3) is an oncogene with prognostic and therapeutic relevance in breast cancer. Mechanistically, EPN3 drives breast tumorigenesis by increasing E-cadherin endocytosis, followed by the activation of a ß-catenin/TCF4-dependent partial epithelial-to-mesenchymal transition (EMT), followed by the establishment of a TGFß-dependent autocrine loop that sustains EMT. EPN3-induced partial EMT is instrumental for the transition from in situ to invasive breast carcinoma, and, accordingly, high EPN3 levels are detected at the invasive front of human breast cancers and independently predict metastatic rather than loco-regional recurrence. Thus, we uncover an endocytic-based mechanism able to generate TGFß-dependent regulatory loops conferring cellular plasticity and invasive behavior.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Neoplasias da Mama/fisiopatologia , Endocitose , Proteínas Adaptadoras de Transporte Vesicular/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Caderinas/genética , Caderinas/metabolismo , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Metástase Neoplásica , Transdução de Sinais , Fator de Transcrição 4/genética , Fator de Transcrição 4/metabolismo , Fator de Crescimento Transformador beta/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
7.
Medicine (Baltimore) ; 99(20): e20231, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443355

RESUMO

BACKGROUND: To systematically evaluate the effects of physical activity on physiological markers in breast cancer survivors. METHODS: A systematic search of the PubMed, Wed of Science, Medline, CNKI and Wanfang Database was performed to identify eligible randomized controlled trials to explore physical activity on physiological markers in breast cancer survivors. STATA version 13.0 (Stata Corp LP, College Station, TX) was used for all statistical analyses. RESULTS: A total of 11 articles with 941 cases were eligible in this meta-analysis. The results of the meta-analysis showed that physical activity could decrease the levels of insulin (SMD = -1.90, 95%CI: -3.2 to -0.60; I = 92.3%, P < .001), insulin-like growth factor 1 (IGF-I) (WMD = -4.67, 95%CI: -23.14 to 13.79; I = 96.2%, P < .001), insulin-like growth factor binding protein-3 (IGFBP-3) (WMD = -20.09, 95%CI: -47.15 to 6.97; I = 93.3%, P < .001). However, compared with the control group, there was not the significant change of insulin-like growth factor 2 (IGF-II), insulin-like growth factor binding protein-1 (IGFBP-1), leptin, adiponectin, glucose, C-reactive protein (CRP), Interleukin-6 (IL-6), Interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-ɑ) levels after the intervention. CONCLUSIONS: Physical activity could improve the insulin function that might be associated with decreasing the levels of IGF-I, IGFBP-3 and insulin in breast cancer survivors.


Assuntos
Biomarcadores/análise , Neoplasias da Mama/sangue , Exercício Físico/fisiologia , Adulto , Biomarcadores/sangue , Neoplasias da Mama/fisiopatologia , Sobreviventes de Câncer , Feminino , Humanos , Insulina/análise , Insulina/sangue , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue
8.
J Bone Miner Metab ; 38(5): 730-736, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32405760

RESUMO

INTRODUCTION: Aromatase inhibitors are known to accelerate bone loss in patients with breast cancer. However, how much AIs affect the efficacy of antiresorptive agents has not been studied. The study aimed to compare the effect of alendronate on bone mineral density (BMD) between patients with and without AI treatment. MATERIALS AND METHODS: In this retrospective study, 90 postmenopausal women with early breast cancer who were being treated with both AI and alendronate 70 mg weekly (ALN + AI), and 90 age- and body mass index (BMI)-matched patients who were only taking alendronate (ALN-only) were analyzed. BMD and bone turnover markers (BTMs) were assessed at the baseline and 12 months. RESULTS: The mean age was 63 years. At baseline, the ALN-only group had lower lumbar spine (LS), femur neck (FN), and total hip (TH) BMD than ALN + AI group. After 1-year of alendronate treatment, the LS and FN BMD were improved more in the ALN-only group than those in the ALN + AI group after adjustments for age, BMI, baseline BMD, diabetes, hypertension, renal function, and previous fracture history [LS BMD: 6.2% (3.1%; 9.2%) in ALN-only, 3.5% (-0.5%; 6.5%) in ALN + AI, p = 0.001; FN BMD: 2.5% (0.3%; 5.7%) in ALN-only, 0.9% (- 1.8%; 3.6%) in ALD + AI, p = 0.032]. BTMs were significantly decreased in both groups, but the changes between groups were similar. CONCLUSION: The effect of alendronate on the LS and FN BMD was attenuated in postmenopausal women who were taking AI compared to those who were not on AI.


Assuntos
Alendronato/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Alendronato/farmacologia , Inibidores da Aromatase/farmacologia , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/efeitos dos fármacos , Neoplasias da Mama/fisiopatologia , Feminino , Colo do Fêmur/efeitos dos fármacos , Colo do Fêmur/fisiopatologia , Humanos , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
Anticancer Res ; 40(4): 2231-2238, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234919

RESUMO

AIM: Acute post-operative pain following modified radical mastectomy (MRM) in patients with breast cancer is challenging for anesthesiologists. This study aimed to prospectively compare the quality outcome of interfascial plane blocks performed with ultrasound guidance, and evaluate the consequences of sharing tasks with the breast surgeon. PATIENTS AND METHODS: The study involved 255 patients scheduled for unilateral MRM, who were divided into two groups: Pecs group: General anesthesia plus ultrasound-guided modified pectoral nerves blocks type I and II, including serratus and parasternal infiltration according to surgical requirements; and Control group: general anesthesia only. Quality was evaluated based on perioperative opioid consumption, reported pain intensity, rescue analgesic requirement, side-effects and length of hospital stay. Moreover, a breast surgeon with expertise in ultrasound-guided breast biopsy was trained to perform the blocks. The patient benefits from regional anesthesia delivered by a non-anesthesiologist were assessed. RESULTS: Significant reductions were noted in all of the following: Intraoperative opioid consumption (p<0.001), Numerating Rating Scale pain scores taken 0 and 24 h after surgery (p<0.001), post-operative analgesic administration (p<0.001), nausea and vomiting at 0, 6, and 12-h intervals (p<0.05), and hospital stay (p<0.001) were observed in the Pecs group compared with the control group. Furthermore, data obtained from patients receiving the block from the surgeon showed comparable benefits with no complications. CONCLUSION: Interfascial plane blocks may be an important alternative protocol in MRM, enhancing patient safety and cost benefits. Improvements in cross-disciplinary expertise through flexibility in the training of professionals with other backgrounds may provide effective analgesia and favorable outcomes.


Assuntos
Anestesia Geral/métodos , Neoplasias da Mama/cirurgia , Mama/cirurgia , Mastectomia Radical Modificada/métodos , Bloqueio Nervoso/métodos , Nervos Torácicos/fisiopatologia , Ultrassonografia de Intervenção/métodos , Adulto , Idoso , Anestesiologistas , Mama/fisiopatologia , Neoplasias da Mama/fisiopatologia , Feminino , Humanos , Mastectomia Radical Modificada/efeitos adversos , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/fisiopatologia , Estudos Prospectivos
10.
Anticancer Res ; 40(4): 1797-1808, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234868

RESUMO

BACKGROUND/AIM: Several studies have investigated the influence of obesity on DNA methylation (DNAm) to find biomarkers associated with the detection of chronic diseases, including breast cancer. The aim of the study was to systematically review studies examining the association of body mass index (BMI) and DNAm in blood or normal breast tissue. MATERIALS AND METHODS: Three scientific literature databases (PubMed, Embase and Web of Science) were screened until May 2018. RESULTS: Twenty-four studies were included along with ours in which we investigated this relation in the normal breast tissue of 40 breast cancer patients. CONCLUSION: BMI-associated CpG sites were highly variable with few identified in less than half of the studies. Nevertheless, a few genes potentially associated with BMI were highlighted in blood (CPT1A, ABCG1, SREBF1 and LGALS3BP) and in normal breast tissue (PTPRN2 and ABLIM2). The variability of the results could be explained by the tissue and cell-specificity of methylation and differences in methodology.


Assuntos
Biomarcadores Tumorais/genética , Índice de Massa Corporal , Neoplasias da Mama/genética , Metilação de DNA/genética , Biomarcadores Tumorais/sangue , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/sangue , Neoplasias da Mama/fisiopatologia , Ilhas de CpG/genética , Epigênese Genética , Feminino , Humanos , Obesidade/sangue , Obesidade/genética , Obesidade/patologia
11.
Arch Biochem Biophys ; 687: 108385, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32335050

RESUMO

MicroRNA-342-3p (miR-342) has been shown to act as a tumor-suppressor in different cancer types. However, the role and therapeutic implications of miR-342 via modulation of Cofilin 1 (CFL1) has not been studied in any type of cancer. Given the importance of Cofilin signalling in breast, this study was undertaken to explore the therapeutic implications of miR-342 and its target CFL1 in breast cancer. Herein, we found that miR-342 was significantly (P < 0.05) downregulated in breast cancer tissues and cell lines. Functional assays revealed that overexpression of miR-342 caused a significant (P < 0.05) inhibition of the proliferation, colony formation, invasion and migration of the MDA-MB-436 and CAMA-1 breast cancer cells via induction of apoptosis. Bioinformatic approaches and the dual luciferase reporter assay confirmed the interaction between miR-342 and its target CFL1. Moreover, we found that CFL1 was aberrantly overexpressed in breast cancer tissues and cell lines. Overexpression of miR-342 caused remarkable depletion in the expression of CFL1 in MDA-MB-436 breast cancer cells. Silencing of CFL1 in CAMA-1 and MDA-MB-436 cells caused remarkable decrease in the proliferation, colony formation and migration of these cells, similar to that of miR-342 ovexpression. However, overexpression of CFL1 in MDA-MB-346 cells could avoid the tumor suppressive effects of miR-342. Our data provide novel information about the implications of miR-342 and its target CFL1 in breast cancer treatment.


Assuntos
Neoplasias da Mama/fisiopatologia , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Cofilina 1/metabolismo , MicroRNAs/metabolismo , Adulto , Idoso , Apoptose/fisiologia , Linhagem Celular Tumoral , Regulação para Baixo/fisiologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Pessoa de Meia-Idade , Regulação para Cima/fisiologia
12.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 47(1): 25-29, ene.-mar. 2020.
Artigo em Espanhol | IBECS | ID: ibc-187070

RESUMO

El cáncer de mama es el que con más frecuecia afecta a las mujeres. Aunque no se ha podido todavía establecer una causa asociada a esta neoplasia, sí se conocen ciertos factores que podrían favorecer este proceso. Se ha investigado la presencia de algunos virus oncogénicos en el cáncer de mama (virus del papiloma humano, virus del tumor mamario del ratón y el virus de Epstein-Barr). Las técnicas moleculares actuales no permiten aplicar los postulados de Koch. Mediante las técnicas moleculares convencionales se ha podido detectar la presencia de estos virus en el 0-86% de los tejidos tumorales mamarios; sin embargo, no se ha mostrado evidencia de la transcripción activa de los genes virales en estos tejidos. Partiendo del criterio de que concentraciones de transcriptos inferiores a 2 ppm son inconsistentes con la participación de un determinado virus, puede concluirse que no existe actualmente ninguna evidencia científica de que un virus conocido esté implicado


Breast cancer is the most common cancer that affects women. Although it is known that certain factors favour this process, it has not yet been possible to establish a cause associated with this neoplasm. The presence of some oncogenic viruses in breast cancer, such as such as human papillomavirus), mouse mammary tumour virus, and Epstein-Barr virus, has been investigated. The Koch postulates cannot be applied with current molecular techniques. Although using conventional molecular techniques it has been possible to detect the presence of these viruses in between 0-86% of breast tumour tissues. However, no evidence of active transcription of the viral genes in these tissues has been demonstrated. Based on the criterion that transcript concentrations lower than 2ppm are inconsistent with the participation of a certain virus, it can be concluded that there is currently no scientific evidence that a known virus is involved


Assuntos
Humanos , Feminino , Neoplasias da Mama/virologia , Infecções Tumorais por Vírus/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/fisiopatologia , Vírus Oncogênicos
13.
Medicine (Baltimore) ; 99(9): e19383, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118786

RESUMO

RATIONALE: Breast metastasis from serous borderline tumor with micro-invasive carcinoma of ovary is a very rare condition. The breast lump as the only clinical presentation is rarely seen in ovarian carcinoma, which may lead to be misdiagnosed, and the mechanism of breast metastasis from ovarian tumors in early stage still needs to be explored. Differentiation from primary breast cancer and extramammary malignancy is crucial because the treatment and prognosis are significantly different. PATIENT CONCERNS: A 33-year-old female presented with a painless, movable, 1.0 × 1.0 cm lump in the upper outer quadrant of the right breast for a month. DIAGNOSES: Breast metastasis of serous borderline tumor with micro-invasive ovarian carcinoma confirmed by pathology and immunohistochemistry. INTERVENTIONS: The patient underwent lumpectomy, bilateral ovarian tumor stripping operation and prophylactic chemotherapy. OUTCOMES: No signs of recurrence have been detected in 1.5 years of follow-up. LESSONS: Distant metastasis may occur in early stage of ovarian carcinoma. It is important to determine the origin of the primary tumor and develop an effective treatment strategy for patients. Imaging findings and pathological diagnostic criteria are important to accurately differentiate between metastasis and primary breast lesions, which may improve the patient's outcomes.


Assuntos
Neoplasias da Mama/diagnóstico , Metástase Neoplásica/diagnóstico , Neoplasias Ovarianas/complicações , Adulto , Neoplasias da Mama/etiologia , Neoplasias da Mama/fisiopatologia , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/etiologia , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Metástase Neoplásica/patologia , Neoplasias Ovarianas/fisiopatologia , Ultrassonografia/métodos
14.
Medicine (Baltimore) ; 99(10): e19345, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150073

RESUMO

OBJECTIVES: Breast cancer susceptibility gene 1/2 (BRCA1/2) is a promising tumor marker in many types of cancer. However, the methylation frequency of BRCA1/2 gene with occurrence risk and survival benefit of patients with breast carcinoma remains controversy. The aim of the present study was to assess the relationship between BRCA1/2 gene promoter methylation and the occurrence and prognosis in breast carcinoma based on a meta-analysis, meanwhile, this article explored the differential expression levels of BRCA1/2 gene promoter methylation in peripheral blood and tumor tissues of breast cancer patients. METHODS: Electronic databases (PubMed, Medline, Cochrane Library, and CNKI) were searched up to June 2019. The number of BRCA1/2 promoter methylation-positive and -negative patients in breast carcinoma patients were measured, and hazard ratio (HR) with 95% confidence interval (CI) for the association between BRCA1/2 gene promoter methylation and the prognosis of breast carcinoma patients. Primary end points were presence of breast cancer, overall survival (OS), disease-free survival (DFS). Statistical analysis was performed with STATA 12.0. RESULTS AND CONCLUSIONS: Fifty-eight articles including 19,084 individuals met full eligibility criteria. We observed that the frequency of BRCA1 gene promoter methylation was higher in breast cancer tissues compared with normal tissues, and the prognostic analysis suggested that BRCA1 gene promoter methylation was significantly associated with poor overall survival and poor disease-free survival. This study also verified that there was no statistically significant difference in the methylation frequency of BRCA1 gene promoter between peripheral blood and tumor tissues in breast cancer patients, which suggests that the detection of BRCA1 promoter methylation in peripheral blood may be a non-invasive and rapid way to monitor the occurrence breast cancer.


Assuntos
Proteína BRCA1/análise , Proteína BRCA2/análise , Neoplasias da Mama/genética , Metilação de DNA/genética , Prognóstico , Proteína BRCA1/sangue , Proteína BRCA2/sangue , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Neoplasias da Mama/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais
15.
BMC Cancer ; 20(1): 113, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32075592

RESUMO

BACKGROUND: Overweight/obesity are strongly implicated in breast cancer development, and weight gain post-diagnosis is associated with greater morbidity and all-cause mortality. The aim of this study was to describe the prevalence of overweight/obesity and the pattern of weight gain after diagnosis of breast cancer amongst Australian women. METHODS: We collected sociodemographic, medical, weight and lifestyle data using an anonymous, self-administered online cross-sectional survey between November 2017 and January 2018 from women with breast cancer living in Australia. The sample consisted mainly of members of the Breast Cancer Network Australia Review and Survey Group. RESULTS: From 309 responses we obtained complete pre/post diagnosis weight data in 277 women, and calculated pre/post Body Mass Index (BMI) for 270 women. The proportion of women with overweight/obesity rose from 48.5% at diagnosis to 67.4% at time of survey. Most women were Caucasian with stage I-III breast cancer (n = 254) or ductal carcinoma in situ (DCIS) (n = 33) and mean age was 59.1 years. The majority of women (63.7%) reported they had gained weight after diagnosis with an average increase of 9.07 kg in this group. Of the women who provided complete weight data, half gained 5 kg or more, 17.0% gained > 20 kg, and 60.7% experienced an increase in BMI of >1 kg/m2. Over half of the women rated their concern about weight as high. Of those women who gained weight, more than half reported that this occurred during the first year after diagnosis. Two-thirds (69.1%) of women aged 35-74 years gained, on average, 0.48 kg more weight per year than age-matched controls. CONCLUSIONS: Although the findings from this survey should be interpreted cautiously due to a limited response rate and self-report nature, they suggest that women in Australia gain a considerable amount of weight after a diagnosis of breast cancer/DCIS (in excess of age-matched data for weight gain) and report high levels of concern about their weight. Because weight gain after breast cancer may lead to poorer outcomes, efforts to prevent and manage weight gain must be prioritized and accelerated particularly in the first year after diagnosis.


Assuntos
Peso Corporal , Neoplasias da Mama/fisiopatologia , Carcinoma Intraductal não Infiltrante/fisiopatologia , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Inquéritos e Questionários/estatística & dados numéricos , Ganho de Peso , Adulto , Idoso , Austrália/epidemiologia , Índice de Massa Corporal , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Carcinoma Intraductal não Infiltrante/diagnóstico , Carcinoma Intraductal não Infiltrante/epidemiologia , Estudos Transversais , Feminino , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
16.
Sci Rep ; 10(1): 2294, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-32042008

RESUMO

Cumulating evidence in Caucasian women suggests a positive association between height and premenopausal breast cancer risk and a negative association with overall adiposity; however data from Latin America are scarce. We investigated the associations between excess adiposity, body shape evolution across life, and risk of premenopausal breast cancer among 406 cases (women aged 20-45) and 406 matched population-based controls from Chile, Colombia, Costa Rica, and Mexico. Negative associations between adult adiposity and breast cancer risk were observed in adjusted models (body mass index (BMI): Odds ratio (OR) per 1 kg/m2 = 0.93; 95% confidence interval = 0.89-0.96; waist circumference (WC): OR per 10 cm = 0.81 (0.69-0.96); hip circumference (HC): OR per 10 cm = 0.80 (0.67-0.95)). Height and leg length were not associated with risk. In normal weight women (18.5 ≤ BMI < 25), women with central obesity (WC > 88 cm) had an increased risk compared to women with normal WC (OR = 3.60(1.47-8.79)). Residuals of WC over BMI showed positive associations when adjusted for BMI (OR per 10 cm = 1.38 (0.98-1.94)). Body shape at younger ages and body shape evolution were not associated with risk. No heterogeneity was observed by receptor status. In this population of Latin American premenopausal women, different fat distributions in adulthood were differentially associated with risk of breast cancer.


Assuntos
Adiposidade/fisiologia , Neoplasias da Mama/epidemiologia , Obesidade Abdominal/epidemiologia , Pré-Menopausa , Circunferência da Cintura/fisiologia , Adulto , Índice de Massa Corporal , Neoplasias da Mama/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Incidência , América Latina/epidemiologia , Pessoa de Meia-Idade , Obesidade Abdominal/fisiopatologia , Fatores de Risco , Adulto Jovem
17.
Support Care Cancer ; 28(11): 5147-5156, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32060704

RESUMO

PURPOSE: This study aimed to identify unobserved distinct latent classes/subgroups of breast cancer (BC) patients in China with respect to various sexual health measures and examine the association of the latent membership with individual characteristics. METHODS: In a cross-sectional study, 123 BC patients were analyzed. Their sexual health was measured using the Female Sexual Functioning Index (FSFI). Latent class analysis (LCA) was used to examine the patterns of sexual health in patients. Associations of the latent class membership with individual characteristics were examined using multinomial logistic regression. RESULTS: Three a priori unknown distinct latent classes of patients were identified with respect to the 19 FSFI sexual health measures: 50 patients (41.6%) were classified in class 1 "No Impairment Group," 49 patients (39.4%) in class 2 "Organic Sexual Dysfunction Group," and 24 patients (19.1%) in class 3 "Poor Sexual Health Group." Income and anxiety were positively, whereas disease duration was negatively associated with the likelihood of being in class 2 than in class 1, patients with recurrence of cancer were likely to be in classes 2 and 3. Patients classified in class 3 were more likely to have better prior body image and have more severe menopausal symptoms, whereas less likely to have better post body image and have better partner relationships. CONCLUSION: The findings revealed the heterogeneity of sexual health among BC patients in China and may guide to identify the high-risk patients and enable early intervention.


Assuntos
Neoplasias da Mama/fisiopatologia , Comportamento Sexual/fisiologia , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/psicologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Renda , Análise de Classes Latentes , Modelos Logísticos , Menopausa/fisiologia , Menopausa/psicologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/fisiopatologia , Recidiva Local de Neoplasia/psicologia , Comportamento Sexual/psicologia , Comportamento Sexual/estatística & dados numéricos , Saúde Sexual/estatística & dados numéricos , Parceiros Sexuais , Inquéritos e Questionários
18.
Sci Rep ; 10(1): 2550, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054969

RESUMO

The intrauterine and early life environments have been linked to the etiology of breast cancer in prior studies. We prospectively examined whether maternal and newborn anthropometric factors as reported by the mother are related to an increased incidence of adult breast cancer in the daughter. We used data from 35,133 mother-daughter dyads of the Nurses' Health Study (NHS) II and the Nurses' Mothers' Cohort Study. In 2001, living mothers of NHS II participants who were free of cancer completed a questionnaire on their pregnancy with the nurse and their nurse daughter's early life experience. During 403,786 years of follow-up, 865 daughters developed incident cases of invasive breast cancer. Nurses with a birthweight of ≥4000 g had a 32% greater risk for breast cancer (multivariable-adjusted hazard ratio (HR) = 1.32, 95% confidence interval (CI) = 1.02-1.71, p-trend = 0.09) compared with those with birthweights of 3000-3499 g. Higher birth length tended to increase risk of premenopausal breast cancer (p for trend = 0.05). We further noted a modest U-shaped relation between maternal weight gain during pregnancy and premenopausal breast cancer incidence in the daughter. Fetal growth may contribute to shaping later life risk for breast cancer, especially prior to menopause.


Assuntos
Neoplasias da Mama/epidemiologia , Desenvolvimento Fetal/fisiologia , Mães , Núcleo Familiar , Adulto , Antropometria , Peso ao Nascer , Neoplasias da Mama/genética , Neoplasias da Mama/fisiopatologia , Estudos de Coortes , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Menopausa/fisiologia , Gravidez , Modelos de Riscos Proporcionais
19.
Phys Ther ; 100(3): 447-456, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32031221

RESUMO

BACKGROUND: Cancer-related fatigue is a symptom commonly reported in survivors of breast cancer and is the most variable symptom. Besides questionnaires like PIPER to assess cancer-related fatigue, there is a need to objectively measure fatigue. OBJECTIVE: The aim of this study was to assess the physiological dimension of fatigue based on acceleration during a 30-second maximal sit-to-stand test. DESIGN: This was a cross-sectional study. METHODS: Linear acceleration from a smartphone placed on the sternum was recorded in 70 survivors of breast cancer. Fourth-degree polynomial adjustment from the acceleration signal to the vertical and anterior-posterior axis was calculated. The fatigue temporal cut-off point was detected as a change in the curve slope of the first maximum point of acceleration. RESULTS: Women were aged 51.8 (8.9) years with a body mass index of 25.4 (5.1) Kg/m2. They performed 23.6 (6.57) number of repetitions. The mean fatigue cut-off point from the total sample was 10.2 (3.1) seconds. LIMITATIONS: Further research should employ time-prolonged tests to study acceleration behavior beyond 30 seconds as well as include a physiological criterion that justifies the nonlinear saturation of the acceleration-based criterion. CONCLUSIONS: This study assessed fatigue through a low-cost and easy-to-use methodology during a functional and widely used test such as 30-second maximal sit-to-stand. This would allow clinicians to assess fatigue in a short-effort exercise to individualize exercise prescription dose, measure changes during intervention, and track fatigue objectively throughout survivorship.


Assuntos
Aceleração , Neoplasias da Mama/fisiopatologia , Sobreviventes de Câncer , Teste de Esforço/instrumentação , Fadiga/diagnóstico , Smartphone/instrumentação , Adulto , Idoso , Neoplasias da Mama/terapia , Estudos Transversais , Teste de Esforço/métodos , Teste de Esforço/estatística & dados numéricos , Fadiga/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Fenômenos Físicos , Postura Sentada , Posição Ortostática , Fatores de Tempo
20.
Phys Ther ; 100(3): 500-508, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32031629

RESUMO

BACKGROUND: Breast cancer treatments often result in upper extremity functional limitations in both the short and long term. Current evidence makes comparisons against a baseline or contralateral limb, but does not consider changes in function associated with aging. OBJECTIVE: The objective of this study was to compare upper extremity function between women treated for breast cancer more than 12 months in the past and women without cancer. DESIGN: This was an observational cross-sectional study. METHODS: Women who were diagnosed with breast cancer and had a mean post-surgical treatment time of 51 months (range = 12-336 months) were compared with women who did not have breast cancer (CTRL group). Self-reported upper extremity function using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and shoulder range of motion, strength, and muscular endurance were measured. Participants were divided into 3 groups: breast cancer involving the nondominant limb (BC-ND), breast cancer involving the dominant limb (BC-DOM), and CTRL. RESULTS: A total of 59 women in the CTRL group, 23 women in the BC-ND group, and 28 women in the BC-DOM group completed measures. Mean DASH scores in women with breast cancer were higher than those of women in the CTRL group, regardless of the limb on which cancer occurred (Cohen d = 1.13; 95% CI = 2.20 to 16.21) Range of motion for the BC-ND group was significantly less for flexion (Cohen d = 1.19, 95% CI = -13.08 to -0.11) and external rotation (Cohen d = 1.11, 95% CI = -18.62 to -1.98) compared with the CTRL group. Strength in the BC-ND group was 23% to 25% lower in the CTRL group for external (Cohen's d = 0.89, 95% CI = 0.09 to 0.12) and internal rotation (Cohen d = 0.92, 95% CI = 0.10 to 0.13). Endurance was not significantly different in the 3 groups. LIMITATIONS: Some participants had rehabilitation, which may have skewed results. The range of post-surgical treatment times was broad, making it difficult to determine when function returned. Muscular endurance measures demonstrated a ceiling effect and large variance, limiting the ability to distinguish differences among participants. These results may not be generalizable to the subset of women who were treated with lumpectomy, sentinel node biopsy, or chest wall radiation alone or who underwent a contralateral prophylactic mastectomy. CONCLUSION: In the long term, women with breast cancer have lower self-reported shoulder function than women without breast cancer. Motion and strength are lower among women who have experienced cancer on the nondominant limb.


Assuntos
Neoplasias da Mama/fisiopatologia , Desempenho Físico Funcional , Amplitude de Movimento Articular/fisiologia , Autorrelato , Articulação do Ombro/fisiopatologia , Extremidade Superior/fisiopatologia , Adulto , Idoso , Análise de Variância , Neoplasias da Mama/terapia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Força Muscular , Medidas de Resultados Relatados pelo Paciente , Resistência Física , Tamanho da Amostra
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