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1.
Medicine (Baltimore) ; 99(40): e22203, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019395

RESUMO

Breast cancer (BC) is a disease of high mortality rate because of high malignant, while early diagnosis and personal management may make a better prognosis possible. This study aimed to establish and validate lncRNAs signatures to improve the prognostic prediction for BC.RNA sequencing data along with the corresponding clinical information of patients with BC were gained from The Cancer Genome Atlas (TCGA). Prognostic differentially expressed lncRNAs were obtained using differentially expressed lncRNAs analysis (P value <.01 and |fold change| > 2) and univariate cox regression (P value <.05). By applying least absolute shrinkage and selection operation (LASSO) Cox regression analysis along with 10-fold cross-validation, 2 lncRNA-based signatures were constructed in the training, test and whole set.A 14-lncRNAs signature and a 10-lncRNAs signature were built for overall survival (OS) and relapse-free survival (RFS) respectively in the 3 sets. BC patients were divided into high-risk groups and low-risk groups depended on median risk score value. Significant differences were found for OS and RFS between 2 groups in the 3 sets. The time-dependent receiver operating characteristic (ROC) curves analysis demonstrated that our lncRNAs signatures had better predictive capacities of survival and recurrence for BC patients as well as enhancing the predictive ability of the tumor node metastasis (TNM) stage system.These results indicate that the 2 lncRNAs signatures with the potential to be biomarkers to predict the prognosis of BC for OS and RFS.


Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , RNA Longo não Codificante/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Curva ROC
2.
Tumour Biol ; 42(10): 1010428320963811, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33028151

RESUMO

This study aimed at investigating the expression of candidate microRNAs (miRs), at initial diagnosis, during neoadjuvant chemotherapy, and after the tumor resection in locally advanced breast cancer patients. Plasma samples were collected from locally advanced breast cancer patients (n = 30) and healthy subjects (n = 20) for the detection of candidate miRs' expression using the real-time quantitative polymerase chain reaction. At initial locally advanced breast cancer diagnosis, the expression of miR-21, miR-181a, and miR-10b was significantly increased, whereas that of miR-145 and let-7a was significantly decreased, compared to the healthy individuals. The diagnostic accuracy of miR-21 was superior to both carcinoembryonic antigen and carcinoma antigen 15-3 as diagnostic biomarkers for locally advanced breast cancer. By the end of the treatment, the expression of altered miRs rebound to control values. The expression levels of candidate plasma miRs are useful diagnostic biomarkers, as well as monitoring a proper response for locally advanced breast cancer patients to the treatment. Furthermore, miR-10b and miR-21 can be considered as predictive biomarkers for progression-free survival.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , MicroRNA Circulante , MicroRNAs , Adulto , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade
3.
Anticancer Res ; 40(9): 5229-5235, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878811

RESUMO

BACKGROUND/AIM: The prolactin receptor (PRLR) is implicated in the tumorigenesis of breast and prostate cancers where it drives cell proliferation, survival, and migration. LFA102 is a humanized monoclonal antibody against PRLR with promising preclinical antitumor activity. To determine the maximum tolerated dose or a recommended dose, and to delineate the pharmacokinetic profile of LFA102 in Japanese patients, we conducted a phase I study. PATIENTS AND METHODS: LFA102 was intravenously infused every 4 weeks to patients with advanced breast or castration-resistant prostate cancer, and the dose increased from 3 to 40 mg/kg. RESULTS: Fourteen patients were treated, and toxicities were reported in 9 (64%) patients. They were all grade 1 or 2, and the most frequently observed toxicity was nausea (3 patients, 21%). No dose-limiting toxicities were observed. LFA102 did not show antitumor activity as a single agent. CONCLUSION: Treatment with LFA102 was well tolerated.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/farmacocinética , Biomarcadores Tumorais , Neoplasias da Mama/etiologia , Neoplasias da Mama/mortalidade , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias de Próstata Resistentes à Castração/etiologia , Neoplasias de Próstata Resistentes à Castração/mortalidade , Resultado do Tratamento
4.
Medicine (Baltimore) ; 99(38): e22331, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957402

RESUMO

Since 2013, trastuzumab emtansine (T-DM1) has been widely used in Japan to treat patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) who were previously administered trastuzumab and a taxane. However, there is no information about the treatment outcomes after exposure to T-DM1 in Japanese patients with HER2-positive MBC. In this study, we aimed to describe the survival outcomes of patients with HER2-positive MBC who received a treatment following T-DM1 and clarify the predictive factors of their prognosis.We retrospectively identified patients with HER2-positive MBC who received T-DM1 between April 1, 2014, and December 31, 2018, at the National Cancer Center Hospital, and focused on the population that received another line of therapy following T-DM1 discontinuation.Thirty patients were available for the outcome analysis. Median progression-free survival (PFS) of the first subsequent therapy was 6.0 months [95% confidence interval (95% CI) 4.1-6.4], whereas the median overall survival (OS) from the first subsequent therapy was 20.6 months (95% CI 13.5 months to not reached). We divided the patients into 2 groups according to their PFS with T-DM1 treatment and compared their PFS with the subsequent therapy. The results revealed a significant difference in the median PFS with the first subsequent treatment between patients with the PFS of less than and more than 3 months [5.1 (95% CI 1.7-6.2) vs 6.2 (95% CI 4.0-11.3) months, P = .03].This is the first study to evaluate the survival outcomes of post-T-DM1 therapy in Japanese patients with HER2-positive MBC. A short PFS with T-DM1 might affect the PFS with a treatment after T-DM1.


Assuntos
Ado-Trastuzumab Emtansina/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2 , Estudos Retrospectivos , Resultado do Tratamento
5.
BMC Bioinformatics ; 21(1): 396, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894041

RESUMO

BACKGROUND: MicroRNAs are a class of important small noncoding RNAs, which have been reported to be involved in the processes of tumorigenesis and development by targeting a few genes. Existing studies show that the imbalance between cell proliferation and apoptosis is closely related to the initiation and development of cancers. However, the impact of miRNAs on this imbalance has not been studied systematically. RESULTS: In this study, we first construct a cell fate miRNA-gene regulatory network. Then, we propose a systematical method for calculating the global impact of miRNAs on cell fate genes based on the shortest path. Results on breast cancer and liver cancer datasets show that most of the cell fate genes are perturbed by the differentially expressed miRNAs. Most of the top-identified miRNAs are verified in the Human MicroRNA Disease Database (HMDD) and are related to breast and liver cancers. Function analysis shows that the top 20 miRNAs regulate multiple cell fate related function modules and interact tightly based on their functional similarity. Furthermore, more than half of them can promote sensitivity or induce resistance to some anti-cancer drugs. Besides, survival analysis demonstrates that the top-ranked miRNAs are significantly related to the overall survival time in the breast and liver cancers group. CONCLUSION: In sum, this study can help to systematically study the important role of miRNAs on proliferation and apoptosis and thereby uncover the key miRNAs during the process of tumorigenesis. Furthermore, the results of this study will contribute to the development of clinical therapy based miRNAs for cancers.


Assuntos
Apoptose/genética , Proliferação de Células/genética , MicroRNAs/metabolismo , Biomarcadores/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Bases de Dados Genéticas , Feminino , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Mensageiro/metabolismo , Análise de Sobrevida
6.
Medicine (Baltimore) ; 99(31): e21211, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756099

RESUMO

RATIONALE: Within a rapidly expanding therapeutic armamentarium, the combination of everolimus (Eve) plus exemestane (Exe) utility needs to be reinstated in hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC). PATIENT CONCERNS: We herein report on a patient affected by HR+ HER2- MBC treated with radical surgery after neoadjuvant chemotherapy, who relapsed early on adjuvant tamoxifen, progressed rapidly on first line anastrozole, and failed treatment with third line capecitabine. DIAGNOSES: Metastatic luminal breast cancer progressed under standard endocrine therapy and chemotherapy. INTERVENTIONS: Third line with Eve plus Exe was given after chemotherapy. OUTCOMES: Patient experienced a 5-year progression free interval. LESSONS: Eve plus Exe remains a valid option in HR+HER2- MBC.


Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma Lobular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Androstadienos/administração & dosagem , Androstadienos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/mortalidade , Carcinoma Lobular/patologia , Everolimo/administração & dosagem , Everolimo/uso terapêutico , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Pré-Menopausa , Intervalo Livre de Progressão
7.
Medicine (Baltimore) ; 99(31): e21487, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756178

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a pandemic in the world and posed a great threat to people's health. Several meta-analyses have indicated that many comorbidities were associated with increased risk of COVID-19 severity or mortality. The original report also showed that the mortality rate of COVID-19 in breast cancer patients is more dependent on comorbidities than previous radiation therapy or current anti-cancer therapy. However, no meta-analysis has focused on this aspect. This systematic review aims to assess whether breast cancer will increase the severity and mortality of patients infected with COVID-19 and to explore which factors that may affect the severity or mortality rate of breast cancer patients with COVID-19. METHODS: We will search the PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Wanfang database from December 1, 2019 to June 30, 2020. Cohort studies comparing the disease severity and mortality of COVID-19 patients with and without breast cancer will be included. Two independent reviewers will assess the risk of bias of the included cohort studies using the modified Newcastle-Ottawa Scale. We will conduct meta-analyses to calculate the risk ratio (RR) and 95% confidence interval (95% CI) using the random-effects model with the Mantel-Haenszel method. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach will be used to rate the quality of the evidence. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will provide comprehensive evidence for medical staff to adopt effective treatment strategies for breast cancer patients during the COVID-19 pandemic. PROSPERO REGISTRATION NUMBER: CRD42020188208.


Assuntos
Betacoronavirus , Neoplasias da Mama/mortalidade , Neoplasias da Mama/virologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Infecções por Coronavirus/virologia , Feminino , Humanos , Metanálise como Assunto , Pandemias , Pneumonia Viral/virologia , Prognóstico , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
8.
Medicine (Baltimore) ; 99(32): e21560, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769897

RESUMO

Breast cancer and ovarian cancer are closely related. The major common risk factors of these 2 types of cancer are likely genetic factors. However, few studies have shown any common characteristics in patients who have both types of these 2 cancers. The purpose of this retrospective study is to explore the clinical characteristics and survival outcomes of patients with both primary breast cancer and primary ovarian cancer.A cohort of patients who had a history of both primary breast cancer and primary ovarian cancer were enrolled, and they received treatment in the Peking Union Medical College Hospital between January 1, 2010, and December 31, 2018. Both descriptive statistics analysis and survival analysis were performed for analysis.A total of 114 patients with both primary breast cancer and primary ovarian cancer were included in the study. The median (range) follow-up was 129.5 (20-492) months. The average interval time between the diagnosis of 2 types of cancer was 79.4 months in patients having ovarian cancer firstly and was 115.9 months in patients having breast cancer firstly. The 5- and 10-year overall survival (OS) rates were 91.5% and 81.7% for patients with ovarian cancer following breast cancer, respectively, and 90.6% and 87.5% for patients with breast cancer following ovarian cancer, respectively. Multivariate analysis revealed that independent predictors of OS were the age of diagnosis of the first tumor and the time interval between two types of tumor in patients with ovarian cancer following breast cancer.Most breast cancer or ovarian cancer occurred within 5 years after being diagnosed with the first tumor, and the interval time was significantly shorter in patients with previous ovarian cancer. The prognosis is likely positively correlated to the interval time between the occurrences of two types of cancer.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias Ovarianas/mortalidade , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo
9.
Medicine (Baltimore) ; 99(32): e21461, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769875

RESUMO

The present study aimed to investigate the prognostic implication of distance from tumor to nipple according to clinicopathological factors with known prognostic value.We retrospectively identified 961 patients of invasive breast cancer from January 2000 to April 2016. Clinicopathological information was extracted from hospital database and distance from tumor to nipple was objectively measured during surgeries. Overall survival (OS) and disease-free survival (DFS) were compared among patients with tumor-nipple distance ≤2, 2 to 5, and >5 cm. Subgroup analyses were performed according to age at diagnosis (≤35 vs >35), tumor size, histological features, treatment, axillary nodal metastasis and lymphovascular invasion.A total of 627 cases were included in statistical analysis. There was no difference detected in OS or DFS among patients with different tumor-nipple distance. Better OS was associated with greater tumor-nipple distance in old patients (HR = 0.582, 95%CI: 0.345-0.982, P = 0.042), while the association between OS and tumor-nipple distance was not observed in young patients. DFS was influenced by tumor-nipple distance in both young (HR = 5.321, 95%CI: 1.151-24.595, P = 0.032) and old (HR = 0.593, 95%CI: 0.385-0.913, P = 0.018) patients with opposite effects.Tumor-nipple distance can be adopted as a prognostic factor of breast cancer and it functions oppositely in young and old patients. Multicenter prospective studies with larger sample size are needed to validate the result.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Mamilos/patologia , Adulto , Fatores Etários , Neoplasias da Mama/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
10.
Future Oncol ; 16(28): 2191-2195, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32857603

RESUMO

Background: Telemedicine is seen as a savior during the COVID-19 pandemic. Materials & methods: This study is a descriptive cross-sectional study conducted with cancer patients who were interviewed via telemedicine from a tertiary care comprehensive oncology center. Results: A total of 421 patients were included in the study and 118 of them (28.0%) were >65 years old. Communication was provided most frequently by voice call (n = 213; 50.5%). The majority of the patients contacted by telemedicine had breast cancer (n = 270; 64.1%). For 135 patients (32.1%) no further examination or intervention was required and the previously planned follow-up visit was postponed by the clinician. Conclusion: This study showed that telemedicine could open a new era for medical oncology specialists.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Sobreviventes de Câncer , Infecções por Coronavirus/prevenção & controle , Oncologia/organização & administração , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Telemedicina/organização & administração , Administração Oral , Adulto , Assistência ao Convalescente/métodos , Assistência ao Convalescente/organização & administração , Assistência ao Convalescente/normas , Assistência ao Convalescente/tendências , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Betacoronavirus/patogenicidade , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Neoplasias da Mama Masculina , Institutos de Câncer/organização & administração , Institutos de Câncer/normas , Institutos de Câncer/tendências , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Estudos Transversais , Feminino , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/tratamento farmacológico , Humanos , Controle de Infecções/organização & administração , Controle de Infecções/normas , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Oncologia/métodos , Oncologia/normas , Oncologia/tendências , Conduta do Tratamento Medicamentoso/organização & administração , Conduta do Tratamento Medicamentoso/normas , Conduta do Tratamento Medicamentoso/tendências , Pessoa de Meia-Idade , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/tratamento farmacológico , Telemedicina/normas , Telemedicina/tendências
11.
Proc Natl Acad Sci U S A ; 117(35): 21420-21431, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32817494

RESUMO

One of the emerging hallmarks of cancer illustrates the importance of metabolic reprogramming, necessary to synthesize the building blocks required to fulfill the high demands of rapidly proliferating cells. However, the proliferation-independent instructive role of metabolic enzymes in tumor plasticity is still unclear. Here, we provide evidence that glutathione peroxidase 8 (GPX8), a poorly characterized enzyme that resides in the endoplasmic reticulum, is an essential regulator of tumor aggressiveness. We found that GPX8 expression was induced by the epithelial-mesenchymal transition (EMT) program. Moreover, in breast cancer patients, GPX8 expression significantly correlated with known mesenchymal markers and poor prognosis. Strikingly, GPX8 knockout in mesenchymal-like cells (MDA-MB-231) resulted in an epithelial-like morphology, down-regulation of EMT characteristics, and loss of cancer stemness features. In addition, GPX8 knockout significantly delayed tumor initiation and decreased its growth rate in mice. We found that these GPX8 loss-dependent phenotypes were accompanied by the repression of crucial autocrine factors, in particular, interleukin-6 (IL-6). In these cells, IL-6 bound to the soluble receptor (sIL6R), stimulating the JAK/STAT3 signaling pathway by IL-6 trans-signaling mechanisms, so promoting cancer aggressiveness. We observed that in GPX8 knockout cells, this signaling mechanism was impaired as sIL6R failed to activate the JAK/STAT3 signaling pathway. Altogether, we present the GPX8/IL-6/STAT3 axis as a metabolic-inflammatory pathway that acts as a robust regulator of cancer cell aggressiveness.


Assuntos
Neoplasias da Mama/enzimologia , Interleucina-6/metabolismo , Janus Quinases/metabolismo , Peroxidases/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Neoplasias da Mama/mortalidade , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Feminino , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Fenótipo , Transdução de Sinais
12.
Lancet Glob Health ; 8(9): e1203-e1212, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32827482

RESUMO

BACKGROUND: Breast cancer is the second leading cause of death from cancer in women in sub-Saharan Africa, yet there are few well characterised large-scale survival studies with complete follow-up data. We aimed to provide robust survival estimates in women in this setting and apportion the survival gaps. METHODS: The African Breast Cancer-Disparities in Outcomes (ABC-DO) prospective cohort study was done at eight hospitals across five sub-Saharan African countries (Namibia, Nigeria, South Africa, Uganda, and Zambia). We prospectively recruited women (aged ≥18 years) who attended these hospitals with suspected breast cancer. Women were actively followed up by use of a telephone call once every 3 months, and a mobile health application was used to keep a dynamic record of follow-up calls due. We collected detailed sociodemographic, clinical, and treatment data. The primary outcome was 3-year overall survival, analysed by use of flexible proportional mortality models, and we predicted survival under scenarios of modified distributions of risk factors. FINDINGS: Between Sept 8, 2014, and Dec 31, 2017, 2313 women were recruited from these eight hospitals, of whom 85 did not have breast cancer. Of the remaining 2228 women with breast cancer, 58 women with previous treatment or recurrence, and 14 women from small racial groups (white and Asian women in South Africa), were excluded. Of the 2156 women analysed, 1840 (85%) were histologically confirmed, 129 (6%) were cytologically confirmed, and 187 (9%) were clinically confirmed to have breast cancer. 2156 (97%) women were followed up for up to 3 years or up to Jan 1, 2019, whichever was earlier. Up to this date, 879 (41%) of these women had died, 1118 (52%) were alive, and 159 (7%) were censored early. 3-year overall survival was 50% (95% CI 48-53), but we observed variations in 3-year survival between different races in Namibia (from 90% in white women to 56% in Black women) and in South Africa (from 76% in mixed-race women to 59% in Black women), and between different countries (44-47% in Uganda and Zambia vs 36% in Nigeria). 215 (10%) of all women had died within 6 months of diagnosis, but 3-year overall survival remained low in women who survived to this timepoint (58%). Among survival determinants, improvements in early diagnosis and treatment were predicted to contribute to the largest increases in survival, with a combined absolute increase in survival of up to 22% in Nigeria, Zambia, and Uganda, when compared with the contributions of other factors (such as HIV or aggressive subtypes). INTERPRETATION: Large variations in breast cancer survival in sub-Saharan African countries indicate that improvements are possible. At least a third of the projected 416 000 breast cancer deaths that will occur in this region in the next decade could be prevented through achievable downstaging and improvements in treatment. Improving survival in socially disadvantaged women warrants special attention. FUNDING: Susan G Komen and the International Agency for Research on Cancer.


Assuntos
Neoplasias da Mama/mortalidade , Adulto , África ao Sul do Saara/epidemiologia , Idoso , Neoplasias da Mama/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida
13.
BMJ ; 370: m2836, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32816842

RESUMO

OBJECTIVE: To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer. DESIGN: Prospective, open label, randomised controlled clinical trial. SETTING: 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada. PARTICIPANTS: 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT). INTERVENTIONS: Random allocation was to the EBRT arm, which consisted of a standard daily fractionated course (three to six weeks) of whole breast radiotherapy, or the TARGIT-IORT arm. TARGIT-IORT was given immediately after lumpectomy under the same anaesthetic and was the only radiotherapy for most patients (around 80%). TARGIT-IORT was supplemented by EBRT when postoperative histopathology found unsuspected higher risk factors (around 20% of patients). MAIN OUTCOME MEASURES: Non-inferiority with a margin of 2.5% for the absolute difference between the five year local recurrence rates of the two arms, and long term survival outcomes. RESULTS: Between 24 March 2000 and 25 June 2012, 1140 patients were randomised to TARGIT-IORT and 1158 to EBRT. TARGIT-IORT was non-inferior to EBRT: the local recurrence risk at five year complete follow-up was 2.11% for TARGIT-IORT compared with 0.95% for EBRT (difference 1.16%, 90% confidence interval 0.32 to 1.99). In the first five years, 13 additional local recurrences were reported (24/1140 v 11/1158) but 14 fewer deaths (42/1140 v 56/1158) for TARGIT-IORT compared with EBRT. With long term follow-up (median 8.6 years, maximum 18.90 years, interquartile range 7.0-10.6) no statistically significant difference was found for local recurrence-free survival (hazard ratio 1.13, 95% confidence interval 0.91 to 1.41, P=0.28), mastectomy-free survival (0.96, 0.78 to 1.19, P=0.74), distant disease-free survival (0.88, 0.69 to 1.12, P=0.30), overall survival (0.82, 0.63 to 1.05, P=0.13), and breast cancer mortality (1.12, 0.78 to 1.60, P=0.54). Mortality from other causes was significantly lower (0.59, 0.40 to 0.86, P=0.005). CONCLUSION: For patients with early breast cancer who met our trial selection criteria, risk adapted immediate single dose TARGIT-IORT during lumpectomy was an effective alternative to EBRT, with comparable long term efficacy for cancer control and lower non-breast cancer mortality. TARGIT-IORT should be discussed with eligible patients when breast conserving surgery is planned. TRIAL REGISTRATION: ISRCTN34086741, NCT00983684.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/cirurgia , Idoso , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Terapia Combinada , Feminino , Humanos , Cuidados Intraoperatórios , Mastectomia Segmentar , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estudos Prospectivos , Dosagem Radioterapêutica , Taxa de Sobrevida
15.
Lancet Oncol ; 21(8): 1023-1034, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32702310

RESUMO

BACKGROUND: Since a national lockdown was introduced across the UK in March, 2020, in response to the COVID-19 pandemic, cancer screening has been suspended, routine diagnostic work deferred, and only urgent symptomatic cases prioritised for diagnostic intervention. In this study, we estimated the impact of delays in diagnosis on cancer survival outcomes in four major tumour types. METHODS: In this national population-based modelling study, we used linked English National Health Service (NHS) cancer registration and hospital administrative datasets for patients aged 15-84 years, diagnosed with breast, colorectal, and oesophageal cancer between Jan 1, 2010, and Dec 31, 2010, with follow-up data until Dec 31, 2014, and diagnosed with lung cancer between Jan 1, 2012, and Dec 31, 2012, with follow-up data until Dec 31, 2015. We use a routes-to-diagnosis framework to estimate the impact of diagnostic delays over a 12-month period from the commencement of physical distancing measures, on March 16, 2020, up to 1, 3, and 5 years after diagnosis. To model the subsequent impact of diagnostic delays on survival, we reallocated patients who were on screening and routine referral pathways to urgent and emergency pathways that are associated with more advanced stage of disease at diagnosis. We considered three reallocation scenarios representing the best to worst case scenarios and reflect actual changes in the diagnostic pathway being seen in the NHS, as of March 16, 2020, and estimated the impact on net survival at 1, 3, and 5 years after diagnosis to calculate the additional deaths that can be attributed to cancer, and the total years of life lost (YLLs) compared with pre-pandemic data. FINDINGS: We collected data for 32 583 patients with breast cancer, 24 975 with colorectal cancer, 6744 with oesophageal cancer, and 29 305 with lung cancer. Across the three different scenarios, compared with pre-pandemic figures, we estimate a 7·9-9·6% increase in the number of deaths due to breast cancer up to year 5 after diagnosis, corresponding to between 281 (95% CI 266-295) and 344 (329-358) additional deaths. For colorectal cancer, we estimate 1445 (1392-1591) to 1563 (1534-1592) additional deaths, a 15·3-16·6% increase; for lung cancer, 1235 (1220-1254) to 1372 (1343-1401) additional deaths, a 4·8-5·3% increase; and for oesophageal cancer, 330 (324-335) to 342 (336-348) additional deaths, 5·8-6·0% increase up to 5 years after diagnosis. For these four tumour types, these data correspond with 3291-3621 additional deaths across the scenarios within 5 years. The total additional YLLs across these cancers is estimated to be 59 204-63 229 years. INTERPRETATION: Substantial increases in the number of avoidable cancer deaths in England are to be expected as a result of diagnostic delays due to the COVID-19 pandemic in the UK. Urgent policy interventions are necessary, particularly the need to manage the backlog within routine diagnostic services to mitigate the expected impact of the COVID-19 pandemic on patients with cancer. FUNDING: UK Research and Innovation Economic and Social Research Council.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias Colorretais/mortalidade , Infecções por Coronavirus/epidemiologia , Neoplasias Esofágicas/mortalidade , Neoplasias Pulmonares/mortalidade , Pneumonia Viral/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Inglaterra/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Pandemias , Análise de Sobrevida , Adulto Jovem
16.
Public Health ; 185: 130-138, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32622220

RESUMO

OBJECTIVES: Health insurance availability and affordability are vital elements in diagnosis and treatment of patients with cancer and thus constitute clinical significance as well. Although past studies have explored the disparity in mortality figures for patients with different insurance statuses, this population-based study is pioneering in analyzing the changes in cancer mortality risks over time amid macroeconomic shifts. STUDY DESIGN: The study uses Surveillance Epidemiology and End Results (SEER) data of 424,889 non-elderly patients with breast, cervical, ovarian, and uterine cancer diagnosed during 2007-2010 and 2011-2015. METHODS: In addition to discussing incidence figures and insurance patterns, the study uses Kaplan-Meier and Cox's proportional hazard models to examine the changes in survival probability and mortality risks for insurance-stratified patients with female-specific cancer across the two time periods. RESULTS: Patients without insurance have an increased risk of mortality over time relative to insured patients. Moreover, uninsured patients face this heightened risk more than Medicaid patients. DISCUSSION: Despite public policy measures as well as advancements in diagnostic facilities and treatment technology, the increased relative mortality of patients without insurance limits the long-term affordability of cancer treatment for economically vulnerable patients in comparison with insured patients.


Assuntos
Cobertura do Seguro/estatística & dados numéricos , Seguro Saúde/estatística & dados numéricos , Neoplasias/mortalidade , Adolescente , Adulto , Neoplasias da Mama/mortalidade , Feminino , Humanos , Incidência , Cobertura do Seguro/economia , Seguro Saúde/economia , Medicaid/economia , Pessoas sem Cobertura de Seguro de Saúde , Pessoa de Meia-Idade , Neoplasias/economia , Neoplasias/epidemiologia , Neoplasias Ovarianas/mortalidade , Fatores de Risco , Programa de SEER , Estados Unidos , Neoplasias do Colo do Útero/mortalidade , Neoplasias Uterinas/mortalidade , Adulto Jovem
17.
PLoS Comput Biol ; 16(7): e1008036, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32628726

RESUMO

The benefits of mammography screening have been controversial, with conflicting findings from various studies. We hypothesize that unmeasured heterogeneity in tumor aggressiveness underlies these conflicting results. Based on published data from the Canadian National Breast Screening Study (CNBSS), we develop and parameterize an individual-based mechanistic model for breast cancer incidence and mortality that tracks five stages of breast cancer progression and incorporates the effects of age on breast cancer incidence and all-cause mortality. The model accurately reproduces the reported outcomes of the CNBSS. By varying parameters, we predict that the benefits of mammography depend on the effectiveness of cancer treatment and tumor aggressiveness. In particular, patients with the most rapidly growing or potentially largest tumors have the highest benefit and least harm from the screening, with only a relatively small effect of age. However, the model predicts that confining mammography to populations with a high risk of acquiring breast cancer increases the screening benefit only slightly compared with the full population.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/mortalidade , Detecção Precoce de Câncer , Mamografia , Adulto , Idoso , Algoritmos , Biologia Computacional , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Modelos Teóricos , Modelos de Riscos Proporcionais , Processos Estocásticos , Resultado do Tratamento
18.
JAMA ; 324(4): 369-380, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32721007

RESUMO

Importance: The influence of menopausal hormone therapy on breast cancer remains unsettled with discordant findings from observational studies and randomized clinical trials. Objective: To assess the association of prior randomized use of estrogen plus progestin or prior randomized use of estrogen alone with breast cancer incidence and mortality in the Women's Health Initiative clinical trials. Design, Setting, and Participants: Long-term follow-up of 2 placebo-controlled randomized clinical trials that involved 27 347 postmenopausal women aged 50 through 79 years with no prior breast cancer and negative baseline screening mammogram. Women were enrolled at 40 US centers from 1993 to 1998 with follow-up through December 31, 2017. Interventions: In the trial involving 16 608 women with a uterus, 8506 were randomized to receive 0.625 mg/d of conjugated equine estrogen (CEE) plus 2.5 mg/d of medroxyprogesterone acetate (MPA) and 8102, placebo. In the trial involving 10 739 women with prior hysterectomy, 5310 were randomized to receive 0.625 mg/d of CEE alone and 5429, placebo. The CEE-plus-MPA trial was stopped in 2002 after 5.6 years' median intervention duration, and the CEE-only trial was stopped in 2004 after 7.2 years' median intervention duration. Main Outcomes and Measures: The primary outcome was breast cancer incidence (protocol prespecified primary monitoring outcome for harm) and secondary outcomes were deaths from breast cancer and deaths after breast cancer. Results: Among 27 347 postmenopausal women who were randomized in both trials (baseline mean [SD] age, 63.4 years [7.2 years]), after more than 20 years of median cumulative follow-up, mortality information was available for more than 98%. CEE alone compared with placebo among 10 739 women with a prior hysterectomy was associated with statistically significantly lower breast cancer incidence with 238 cases (annualized rate, 0.30%) vs 296 cases (annualized rate, 0.37%; hazard ratio [HR], 0.78; 95% CI, 0.65-0.93; P = .005) and was associated with statistically significantly lower breast cancer mortality with 30 deaths (annualized mortality rate, 0.031%) vs 46 deaths (annualized mortality rate, 0.046%; HR, 0.60; 95% CI, 0.37-0.97; P = .04). In contrast, CEE plus MPA compared with placebo among 16 608 women with a uterus was associated with statistically significantly higher breast cancer incidence with 584 cases (annualized rate, 0.45%) vs 447 cases (annualized rate, 0.36%; HR, 1.28; 95% CI, 1.13-1.45; P < .001) and no significant difference in breast cancer mortality with 71 deaths (annualized mortality rate, 0.045%) vs 53 deaths (annualized mortality rate, 0.035%; HR, 1.35; 95% CI, 0.94-1.95; P= .11). Conclusions and Relevance: In this long-term follow-up study of 2 randomized trials, prior randomized use of CEE alone, compared with placebo, among women who had a previous hysterectomy, was significantly associated with lower breast cancer incidence and lower breast cancer mortality, whereas prior randomized use of CEE plus MPA, compared with placebo, among women who had an intact uterus, was significantly associated with a higher breast cancer incidence but no significant difference in breast cancer mortality.


Assuntos
Neoplasias da Mama/epidemiologia , Estrogênios Conjugados (USP)/efeitos adversos , Terapia de Reposição Hormonal/efeitos adversos , Histerectomia , Acetato de Medroxiprogesterona/efeitos adversos , Idoso , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/mortalidade , Neoplasias da Mama/prevenção & controle , Estrogênios Conjugados (USP)/uso terapêutico , Feminino , Seguimentos , Humanos , Histerectomia/efeitos adversos , Incidência , Acetato de Medroxiprogesterona/uso terapêutico , Pessoa de Meia-Idade , Pós-Menopausa , Risco
19.
Anticancer Res ; 40(7): 3973-3981, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620640

RESUMO

BACKGROUND/AIM: HER2-positive breast cancers eventually relapse in about one third of patients. Is anti-HER2-directed therapy with Herceptin® (trastuzumab) effective in re-treatment? Between 2008 and 2018, 216 patients with recurrent HER2-positive breast cancer (BC) were re-treated with Herceptin (HER) during first-line therapy. This study assessed the effectiveness and tolerability of re-treatment with HER. PATIENTS AND METHODS: After approval from Ethical committee, the NIS was conducted according to German Drug Act. Re-treatment with HER was documented at routine visits starting with a basic observational period of maximum 12 months and a follow-up period of maximum additional four years. RESULTS: HER2-positive BC relapsed after a median of 36.5 months (mos). Patients were re-treated with HER +/- chemotherapy +/- endocrine therapy. HER-containing regimens resulted in median progression-free survival (mPFS) of 12.7 (95%CI=10.5-14.8) mos and overall survival (OS-2) of 31.6 mos (95%CI=28.8-38.4) since recurrence diagnosis. Differentiation of recurrence types (local, visceral, non-visceral) unfolded worst prognosis for patients with visceral metastases. Cardiac monitoring within this non-interventional study (NIS) did not result in new safety concerns. CONCLUSION: Re-therapy with HER in the first-line setting of advanced HER2-positive breast cancer is effective and without unexpected or intensified adverse events.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Retratamento , Adulto Jovem
20.
J Comput Assist Tomogr ; 44(4): 605-609, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697532

RESUMO

OBJECTIVE: The aim of the study was to determine abdominal and breast adipose tissue parameters on 18-fluorodeoxyglucose positron emission tomography/computed tomography (CT) that may serve as outcome predictors in breast angiosarcoma patients. MATERIALS: Women with breast angiosarcoma (n = 13) who underwent 18-fluorodeoxyglucose positron emission tomography/CT were identified. A control group was selected (n = 25). Abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) were assessed on unenhanced computed tomographies. Breast adipose tissue (BAT) volumes of the uninvolved breast were quantified. Metabolic activity of VAT, SAT, and BAT was calculated (standardized uptake value [SUV]). RESULTS: Breast angiosarcoma patients had higher metabolic activity of VAT compared with controls (SUV 0.93 ± 0.39 vs 0.64 ± 0.11, P = 0.044). Within the patient group, there were 6 deaths (46.2%). Patients who died had higher SAT activity (SUV 0.52 ± 0.24 vs 0.29 ± 0.06, P = 0.027) and higher BAT metabolic activity (SUV 0.48 ± 0.20 vs 0.27 ± 0.11, P = 0.045) compared with nondeceased patients. CONCLUSIONS: Patients with breast angiosarcoma have higher metabolic activity of VAT. Higher abdominal SAT and higher BAT metabolic activity of the uninvolved breast might predict mortality.


Assuntos
Gordura Abdominal/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/mortalidade , Hemangiossarcoma/diagnóstico por imagem , Hemangiossarcoma/mortalidade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Estudos de Casos e Controles , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
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