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1.
Anticancer Res ; 41(9): 4619-4627, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475090

RESUMO

BACKGROUND: The real-world outcomes of patients with advanced invasive lobular carcinoma (ILC) of the breast are unclear because of its rarity. PATIENTS AND METHODS: We identified 435 patients with estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced breast cancer treated at our Institute between 2002 and 2019, and analyzed their outcomes retrospectively. RESULTS: We identified 29 patients with advanced ILC. At presentation, they had a lower rate of lung metastasis (p=0.0053) but a higher rate of stomach metastasis (p=0.0379) compared with other patients with advanced breast cancer. Median overall survival did not differ; however, multivariate analyses showed that ILC histopathology was a risk factor for poorer overall survival (hazard ratio=3.43, p=0.0038) in patients with de novo stage IV ER+ HER2- breast cancer. Patients with ILC showed a markedly different patten of subsequent metastasis, such as less in the lung and more in the stomach, leptomeninges, and bone marrow. CONCLUSION: According to our retrospective study, in patients with de novo stage IV ER+ HER2- breast cancer, ILC histopathology was associated with increased risk of death.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/mortalidade , Carcinoma Lobular/metabolismo , Carcinoma Lobular/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
2.
Lancet Oncol ; 22(9): 1301-1311, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34416159

RESUMO

BACKGROUND: Female breast cancer is the most commonly diagnosed cancer in the world, with wide variations in reported survival by country. Women in low-income and middle-income countries (LMICs) in particular face several barriers to breast cancer services, including diagnostics and treatment. We aimed to estimate the potential impact of scaling up the availability of treatment and imaging modalities on breast cancer survival globally, together with improvements in quality of care. METHODS: For this simulation-based analysis, we used a microsimulation model of global cancer survival, which accounts for the availability and stage-specific survival impact of specific treatment modalities (chemotherapy, radiotherapy, surgery, and targeted therapy), imaging modalities (ultrasound, x-ray, CT, MRI, PET, and single-photon emission computed tomography [SPECT]), and quality of cancer care, to simulate 5-year net survival for women with newly diagnosed breast cancer in 200 countries and territories in 2018. We calibrated the model to empirical data on 5-year net breast cancer survival in 2010-14 from CONCORD-3. We evaluated the potential impact of scaling up specific imaging and treatment modalities and quality of care to the mean level of high-income countries, individually and in combination. We ran 1000 simulations for each policy intervention and report the means and 95% uncertainty intervals (UIs) for all model outcomes. FINDINGS: We estimate that global 5-year net survival for women diagnosed with breast cancer in 2018 was 67·9% (95% UI 62·9-73·4) overall, with an almost 25-times difference between low-income (3·5% [0·4-10·0]) and high-income (87·0% [85·6-88·4]) countries. Among individual treatment modalities, scaling up access to surgery alone was estimated to yield the largest survival gains globally (2·7% [95% UI 0·4-8·3]), and scaling up CT alone would have the largest global impact among imaging modalities (0·5% [0·0-2·0]). Scaling up a package of traditional modalities (surgery, chemotherapy, radiotherapy, ultrasound, and x-ray) could improve global 5-year net survival to 75·6% (95% UI 70·6-79·4), with survival in low-income countries improving from 3·5% (0·4-10·0) to 28·6% (4·9-60·1). Adding concurrent improvements in quality of care could further improve global 5-year net survival to 78·2% (95% UI 74·9-80·4), with a substantial impact in low-income countries, improving net survival to 55·3% (42·2-67·8). Comprehensive scale-up of access to all modalities and improvements in quality of care could improve global 5-year net survival to 82·3% (95% UI 79·3-85·0). INTERPRETATION: Comprehensive scale-up of treatment and imaging modalities, and improvements in quality of care could improve global 5-year net breast cancer survival by nearly 15 percentage points. Scale-up of traditional modalities and quality-of-care improvements could achieve 70% of these total potential gains, with substantial impact in LMICs, providing a more feasible pathway to improving breast cancer survival in these settings even without the benefits of future investments in targeted therapy and advanced imaging. FUNDING: Harvard T H Chan School of Public Health, and National Cancer Institute P30 Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Saúde Global , Acesso aos Serviços de Saúde , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Simulação por Computador , Países em Desenvolvimento , Feminino , Disparidades em Assistência à Saúde , Humanos , Qualidade da Assistência à Saúde , Taxa de Sobrevida
3.
Medicine (Baltimore) ; 100(33): e26949, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414958

RESUMO

BACKGROUND: Ovarian function suppressor (OFS) plus either tamoxifen (TAM) or aromatase inhibitor (AI) could improve the survival outcome for premenopausal hormone receptor-positive (HR+) breast cancer. However, the optimal OFS-based regimen and medication duration remain uncertain. This article aims to systematically evaluate the OFS-based adjuvant endocrine therapy for premenopausal breast cancer. METHODS: We searched several public databases from January 1980 to November 2020. A random model was adopted in this meta-analysis. We used the hazard ratio (HR) with a 95% confidence interval (CI) for the statistical analysis of efficacy. The primary outcome measures included overall survival and disease-free survival. RESULTS: A total of 32 articles with 37,224 cases were included in this network meta-analysis. OFS+TAM improved 5-year disease-free survival (HR -0.09, 95% CI -0.16 to -0.01) and 5-year overall survival (HR -0.18, 95% CI -0.33 to -0.03) compared with TAM monotherapy. For OFS+AI, although the 5-year disease-free survival was improved (HR -0.18, 95% CI -0.29 to -0.08), the 5-year overall survival was not improved (HR -0.13, 95% CI -0.43 to 0.18). In subgroup analysis, both OFS+AI and OFS+TAM showed a protective effect in stage I-III patients compared with stage I-II patients. For the course of therapy, OFS+TAM for 2-years could achieve clinical benefit and the best course of therapy of OFS+AI still waits for further study. CONCLUSIONS: OFS+TAM might be a better option than OFS+AI for premenopausal intensive adjuvant endocrine therapy. Stage III patients are more suitable for the OFS-based therapy. For the medication duration, the 2-years course of OFS+TAM could be effective. This analysis provides helpful information for selecting therapeutic regimen in intensive adjuvant endocrine therapy and identifying the target population.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Tamoxifeno/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Estadiamento de Neoplasias , Metanálise em Rede , Análise de Sobrevida
4.
Medicine (Baltimore) ; 100(33): e26870, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414938

RESUMO

OBJECTIVE: The purpose of this study is to investigate whether aspirin improves the prognosis of breast cancer patients by meta analysis. METHODS: Searched PubMed, EMBASE, and other databases for literature on the relationship between aspirin use and breast cancer prognosis, with the deadline of October 2019. The related results of all-cause death, breast cancer-specific death, and breast cancer recurrence/metastasis were extracted to combine the effect amount. The sensitivity analysis and published bias analysis were carried out for the included data. Stata12.0 software was used to complete all statistical analysis. RESULTS: A total of 13 papers were included in the study, including 142,644 breast cancer patients. The results of meta-analysis showed that patients who took aspirin were associated with lower breast cancer-specific death (HR = 0.69, 95% CI = 0.61-0.76), all-cause death (HR = 0.78, 95% CI = 0.71-0.84), and risk of recurrence/metastasis (HR = 0.91, 95% CI: 0.82-1.00). CONCLUSIONS: Aspirin use may improve all-cause mortality, specific mortality, and risk of recurrence/metastasis in patients with breast cancer.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/prevenção & controle , Feminino , Humanos , Recidiva Local de Neoplasia/prevenção & controle , Prognóstico , Taxa de Sobrevida
5.
Medicine (Baltimore) ; 100(31): e26745, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397816

RESUMO

BACKGROUND: To assess the prognostic capability of the maximum standardized uptake values (SUVmax) measured in the primary tumor and axillary lymph nodes (ALNs) by pretreatment fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography and analyze outcomes according to the molecular breast cancer subtypes. METHODS: The databases were systematically searched using keywords for breast cancer, positron emission tomography/computed tomography, and SUVmax; the extracted studies reported at least 1 form of survival data, event-free survival (EFS) and overall survival. Comparative analyses of the pooled hazard ratios (HRs) for EFS and overall survival were performed to assess their correlations with SUVmax. The pooled HR was estimated using random-effects model according to the results of heterogeneity. RESULTS: Thirteen eligible studies comprising 3040 patients with breast cancer were included. The pooled HRs of high SUVmax in the primary tumor and ALN were 3.01 (95% CI 1.83-4.97, P < .00001; I2 = 82%) and 3.72 (95% CI 1.15-12.01; I2 = 92%; P = .03), respectively. Patients with higher SUVmax demonstrated a poorer survival prognosis. Furthermore, comparative analyses according to the molecular subtypes demonstrated that the SUVmax in the primary tumor or ALN can be a predictive parameter in patients with the luminal subtype disease. Subtype analysis results indicated a significant association of the luminal group, with a HR of 2.65 (95% CI 1.31-5.37; I2 = 27%; P = .007). CONCLUSIONS: SUVmax from pretreatment is a significant prognostic factor for EFS in patients with breast cancer. Despite several limitations, correlation with molecular subtype (luminal type) was demonstrated. Further large-scale studies are required to investigate the precise prognostic capability of SUVmax.


Assuntos
Neoplasias da Mama/complicações , Neoplasias da Mama/genética , Valor Preditivo dos Testes , Neoplasias da Mama/mortalidade , Feminino , Humanos , Imunofenotipagem
6.
Medicine (Baltimore) ; 100(33): e26896, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414945

RESUMO

PURPOSE: Obesity strongly affects the prognosis of various malignancies, including breast cancer. Leptin (LEP) may be associated with obesity and breast cancer prognosis. The purpose of our study was to determine the prognostic value of LEP in breast cancer. METHOD: We conducted a multi-omic analysis to determine the prognostic role of LEP. Different public bioinformatics platforms (Oncomine, Gene Expression Profiling Interactive Analysis, University of California Santa Cruz Xena, bc-GenExMiner, PrognoScan database, R2-Kaplan-Meier Scanner, UALCAN, Search Tool for the Retrieval of Interacting Genes/Proteins database , and The Database for Annotation, Visualization and Integrated Discovery) were used to evaluate the roles of LEP. Clinicopathological variables were evaluated. RESULTS: LEP was downregulated in breast cancer tissues compared to levels in normal tissues. By co-expressed gene analysis, a positive correlation between LEP and SLC19A3 was observed. Based on the clinicopathological analysis, low LEP expression was associated with older age, higher stage, lymph node status, human epidermal growth factor receptor 2 (HER2) status, estrogen receptor (ER+) positivity, and progesterone receptor (PR+) positivity. Kaplan-Meier survival analysis showed that low LEP expression indicated a poorer prognosis. LEP is hypermethylated in breast cancer tissues in PrognoScan and R2-Kaplan Meier Scanner, and low LEP expression was correlated with poor prognosis. LEP protein-protein interactions were analyzed using Search Tool for the Retrieval of Interacting Genes/Proteins database. Gene ontology analysis results showed that cellular component is mainly associated with the endosome lumen, cytosol, and secretory granules and is upregulated. For the biological process energy reserve, metabolic processes exhibited the greatest regulation compared to the others. In molecular function, it was mainly enriched in a variety of combinations, but hormone activity showed the highest regulation. CONCLUSION: Our study provides evidence for the prognostic role of LEP in breast cancer and as a novel potential therapeutic target in such malignancies. Nevertheless, further validation is required.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , Leptina/genética , Neoplasias da Mama/mortalidade , Correlação de Dados , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
7.
Medicine (Baltimore) ; 100(29): e26737, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398051

RESUMO

ABSTRACT: Cutaneous metastasis (CM) occurs infrequently and usually presents during the later stages of cancer, and has a poor prognosis. Although there are insufficient current data, cancer treatment changes could have a positive impact on the outcome. This retrospective study aimed to review the pattern and prognosis of CM in patients with solid malignancy in a tertiary cancer center in Thailand.We reviewed the medical records of cancer patients diagnosed with CM between October 2009 and August 2015 at Chulabhorn Hospital, a tertiary cancer center in Thailand. Patients with primary skin cancer and hematological malignancies were excluded. We collected and analyzed data, including the time of cancer diagnosis and CM, type of cancer, clinical characteristics, and survival outcome.Of 11,418 patients, there were 33 (0.3%) were diagnosed with CM. Breast cancer was the most common primary cancer (12 cases, 36%). Skin nodules were commonly detected on the anterior chest wall. Also, 79% of CM patients had concomitant visceral metastasis. The median overall survival of those with CM was 9.21 months (95% confidence interval 4.75-83.38 months) regardless of presentation either at onset or disease recurrence (P = .083). However, the change of management was affected in 78% diagnosed with a later stage of CM. No statistical difference in survival was observed between breast cancer and non-breast cancer patients (8.79 vs 9.21 months, P = .613).Despite CM being a sign of poor prognosis, it may still be an indicator for changing cancer patients' treatment. Hence, early CM diagnosis and prompt novel therapy may positively affect outcomes for cancer patients.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Humanos , Masculino , Registros Médicos , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/secundário , Análise de Sobrevida , Centros de Atenção Terciária , Tailândia/epidemiologia
8.
Breast ; 59: 301-307, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34385028

RESUMO

PURPOSE: To examine clinicodemographic determinants associated with breast cancer survivorship follow-up during COVID-19. METHODS: We performed a retrospective, population-based cohort study including early stage (Stage I-II) breast cancer patients who underwent resection between 2006 and 2018 in a New York City hospital system. The primary outcome was oncologic follow-up prior to and during the COVID-19 pandemic. Secondary analyses compared differences in follow-up by COVID-19 case rates stratified by ZIP code. RESULTS: A total of 2942 patients with early-stage breast cancer were available for analysis. 1588 (54%) of patients had attended follow-up in the year prior to the COVID-19 period but failed to continue to follow-up during the pandemic, either in-person or via telemedicine. 1242 (42%) patients attended a follow-up appointment during the COVID-19 pandemic. Compared with patients who did not present for follow-up during COVID-19, patients who continued their oncologic follow-up during the pandemic were younger (p = 0.049) more likely to have received adjuvant radiation therapy (p = 0.025), and have lower household income (p = 0.031) on multivariate modeling. When patients who live in Bronx, New York, were stratified by ZIP code, there was a modest negative association (r = -0.56) between COVID-19 cases and proportion of patients who continued to follow-up during the COVID-19 period. CONCLUSION: We observed a dramatic disruption in routine breast cancer follow-up during the COVID-19 pandemic. Providers and health systems should emphasize reintegrating patients who missed appointments during COVID-19 back into regular surveillance programs to avoid significant morbidity and mortality from missed breast cancer recurrences.


Assuntos
Neoplasias da Mama/mortalidade , COVID-19/psicologia , Sobreviventes de Câncer/psicologia , Sobrevivência , Adolescente , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , COVID-19/epidemiologia , Estudos de Coortes , Feminino , Hospitais Urbanos , Humanos , Masculino , Mastectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Cidade de Nova Iorque/epidemiologia , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Adulto Jovem
9.
Anticancer Res ; 41(8): 4133-4141, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281884

RESUMO

BACKGROUND/AIM: Advanced/recurrent breast cancer (ARBC) still has a poor prognosis; therefore, new treatment strategies are required. In this retrospective study, we aimed to investigate the efficacy of immune-cell therapy using T lymphocytes activated in vitro with or without dendritic cell vaccination in combination with standard therapies in terms of the survival of patients with ARBC. PATIENTS AND METHODS: A total of 127 patients with ARBC were enrolled in this study. The correlation between overall survival and various clinical factors of each ARBC subset was examined by univariate and multivariate analyses. RESULTS: Multivariate analysis demonstrated that performance status (PS) 0, the absence of prior chemotherapy, liver/pleural metastasis, and the presence of combined surgery in ARBC and PS 0 or the absence of liver metastasis in the HR+/HER- subset are indications for immune-cell therapy. CONCLUSION: A survival benefit could be potentially obtained by a combination of immune-cell therapy with other therapies in ARBC patients.


Assuntos
Neoplasias da Mama/terapia , Terapia Baseada em Transplante de Células e Tecidos , Células Dendríticas/transplante , Imunoterapia , Recidiva Local de Neoplasia/terapia , Linfócitos T/transplante , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos
10.
Cancer Epidemiol ; 73: 101970, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34216956

RESUMO

BACKGROUND: Screening mammography for breast cancer (BC) is a current strategy that reduces the mortality of BC by up to 30 %. Although mastectomy has been an important component of treatment for decades, conservative surgery (lumpectomy) has become the gold-standard approach for most cases, yet it depends on early detection of the BC. METHODS: This was an epidemiological study performed through DATASUS (2010-2018). We evaluated the temporal trend of screening mammograms, deaths from BC, and surgical procedures at national, regional and state levels. Statistical analysis was performed on VassarStat®-Website for Statistical Computation (Vassar College, New York, USA) and the R-software (R Foundation, v.4.0.3). RESULTS: During 2010-2018 there were 67,392 oncological mastectomies and 48,567 lumpectomies in Brazil's health system. Mastectomies decreased in the Northeast (-3.67 % ± 0.43 per year) and in Bahia state (-3.58 % ± 0.24 per year). Lumpectomies increased in Brazil (median 2.19 (-9.6 to 20.96)), the Northeast (median -12.07 (-25.8 to 9.43)) and Bahia (median 0.16 (-29.1 to 1.9)). Also, screening mammograms increased in Brazil (3.29 % ± 0.43), the Northeast (6.36 % ± 0.49) and Bahia (5.51 % ± 0.31), with 35,317,728 exams during this period. Deaths from BC increased annually in Brazil (+4.13 % ± 0.86), the Northeast (+4.76 % ± 1.45) and Bahia (+5.65 % ± 0.83). CONCLUSION: The number of mammograms related to the screening program increased in the years 2010-2018 in Brazil. Furthermore, we identified an increase in lumpectomies as opposed to mastectomies, and this approach is associated with a reduction in hospitalization days by almost a half, which in turn might result in a cost decrease and probably an earlier return to work.


Assuntos
Neoplasias da Mama , Detecção Precoce de Câncer , Mamografia , Mastectomia , Brasil/epidemiologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Humanos , Mamografia/estatística & dados numéricos , Mastectomia/métodos , Mastectomia/estatística & dados numéricos , Mastectomia Segmentar/estatística & dados numéricos , Avaliação de Programas e Projetos de Saúde
11.
J Steroid Biochem Mol Biol ; 212: 105947, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34214604

RESUMO

Conflicting results have been reported on the association of blood vitamin D level with prognosis in women with breast cancer. This meta-analysis aimed to evaluate the association between blood 25-hydroxyvitamin D level and survival outcomes in female breast cancer patients. Two authors independently searched PubMed and Embase databases from their inception to August 25, 2020. Prospective or retrospective cohort studies evaluating the association between blood 25-hydroxyvitamin D level and survival outcomes in women with breast cancer were included. Outcome measures included overall survival (OS), breast cancer-specific survival (BCSS), and disease-free survival (DFS). Twelve studies involving 8574 female breast cancer patients were identified and analyzed. When compared the lowest with the highest category of 25-hydroxyvitamin D level, the pooled adjusted hazard ratio (HR) was 1.57 (95 % confidence interval [CI] 1.35-1.83) for OS, 1.98 (95 % CI 1.55-2.53) for DFS, and 1.44 (95 % CI 1.14-1.81) for BCSS. This meta-analysis indicates that lower blood 25-hydroxyvitamin D level is significantly associated with reduced survival among female breast cancer patients. Additional clinical trials are required to investigate whether vitamin D supplement can improve survival outcomes in these patients.


Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Vitamina D/análogos & derivados , Vitaminas/sangue , Feminino , Humanos , Vitamina D/sangue
12.
Breast ; 59: 102-109, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34225090

RESUMO

BACKGROUND: The COVID-19 pandemic is a significant worldwide health crisis. Breast cancer patients with COVID-19 are fragile and require particular clinical care. This study aimed to identify the clinical characteristics of breast cancer patients with COVID-19 and the risks associated with anti-cancer treatment. METHODS: The medical records of breast cancer patients with laboratory-confirmed COVID-19 were collected among 9559 COVID-19 patients from seven designated hospitals from 13th January to 18th March 2020 in Hubei, China. Univariate and multivariate analyses were performed to assess risk factors for COVID-19 severity. RESULTS: Of the 45 breast cancer patients with COVID-19, 33 (73.3%) developed non-severe COVID-19, while 12 (26.7%) developed severe COVID-19, of which 3 (6.7%) patients died. The median age was 62 years, and 3 (6.7%) patients had stage IV breast cancer. Univariate analysis showed that age over 75 and the Eastern Cooperative Oncology Group (ECOG) score were associated with COVID-19 disease severity (P < 0.05). Multivariate analysis showed that patients who received chemotherapy within 7 days had a significantly higher risk for severe COVID-19 (logistic regression model: RR = 13.886, 95% CI 1.014-190.243, P = 0.049; Cox proportional hazards model: HR = 13.909, 95% CI 1.086-178.150, P = 0.043), with more pronounced neutropenia and higher LDH, CRP and procalcitonin levels than other patients (P < 0.05). CONCLUSIONS: In our breast cancer cohort, the severity of COVID-19 could be associated with baseline factors such as age over 75 and ECOG scores. Chemotherapy within 7 days before symptom onset could be a risk factor for severe COVID-19, reflected by neutropenia and elevated LDH, CRP and procalcitonin levels.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , COVID-19/diagnóstico , Neutropenia/etiologia , SARS-CoV-2/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/complicações , Neoplasias da Mama/mortalidade , Proteína C-Reativa , China/epidemiologia , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Pessoa de Meia-Idade , Neutropenia/epidemiologia , Pandemias , Pró-Calcitonina/sangue , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
13.
N Engl J Med ; 385(5): 395-405, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34320285

RESUMO

BACKGROUND: For postmenopausal women with hormone-receptor-positive breast cancer, the most effective duration for adjuvant therapy with an aromatase inhibitor remains unclear. METHODS: In this prospective, phase 3 trial, we randomly assigned postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy to receive the aromatase inhibitor anastrozole for an additional 2 years (2-year group, receiving a total of 7 years) or an additional 5 years (5-year group, receiving a total of 10 years). The primary end point was disease-free survival. The primary analysis included all the patients who were still participating in the trial and who had no recurrence 2 years after randomization (i.e., when treatment in the 2-year group had ended). Secondary end points were overall survival, contralateral breast cancer, second primary cancer, and clinical bone fracture. RESULTS: Among the 3484 women who were enrolled in the trial, 3208 remained in the trial without disease progression after the first 2 years of extended anastrozole treatment following randomization. Among these women, disease progression or death occurred in 335 women in each treatment group in the primary-analysis set at 8 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P = 0.90). No between-group differences occurred in most secondary end points, and subgroup analyses did not indicate differences in any particular subgroup. The risk of clinical bone fracture was higher in the 5-year group than in the 2-year group (hazard ratio, 1.35; 95% CI, 1.00 to 1.84). CONCLUSIONS: In postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy, extending hormone therapy by 5 years provided no benefit over a 2-year extension but was associated with a greater risk of bone fracture. (Funded by AstraZeneca and the Austrian Breast and Colorectal Cancer Study Group; ABCSG-16/SALSA ClinicalTrials.gov number, NCT00295620.).


Assuntos
Anastrozol/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Administração Oral , Idoso , Anastrozol/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Receptores de Estrogênio , Receptores de Progesterona , Tamoxifeno/uso terapêutico
14.
Cell Prolif ; 54(8): e13088, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34240781

RESUMO

OBJECTIVES: Breast cancer-amplified sequence 3 (BCAS3) was initially found to be amplified in human breast cancer (BRCA); however, there has been little consensus on the functions of BCAS3 in breast tumours. MATERIALS AND METHODS: We analysed BCAS3 expression in BRCA using bio-information tools. Affinity purification and mass spectrometry were employed to identify BCAS3-associated proteins. GST pull-down and ubiquitination assays were performed to analyse the interaction mechanism between BCAS3/p53 and CUL4A-RING E3 ubiquitin ligase (CRL4A) complex. BCAS3 was knocked down individually or in combination with p53 in MCF-7 cells to further explore the biological functions of the BCAS3/p53 axis. The clinical values of BCAS3 for BRCA progression were evaluated via semiquantitative immunohistochemistry (IHC) analysis and Cox regression. RESULTS: We reported that the expression level of BCAS3 in BRCA was higher than that in adjacent normal tissues. High BCAS3 expression promoted growth, inhibited apoptosis and conferred chemoresistance in breast cancer cells. Mechanistically, BCAS3 overexpression fostered BRCA cell growth by interacting with the CRL4A complex and promoting ubiquitination and proteasomal degradation of p53. Furthermore, BCAS3 could regulate cell growth, apoptosis and chemoresistance through a p53-mediated mechanism. Clinically, BCAS3 overexpression was significantly correlated with a malignant phenotype. Moreover, higher expression of BCAS3 correlates with shorter overall survival (OS) in BRCA. CONCLUSIONS: The functional characterization of BCAS3 offers new insights into the oncogenic properties and chemotherapy resistance in breast cancer.


Assuntos
Neoplasias da Mama/patologia , Proteínas de Neoplasias/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Proliferação de Células , Proteínas Culina/metabolismo , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Prognóstico , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Taxa de Sobrevida , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
15.
Anticancer Res ; 41(8): 3899-3904, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281852

RESUMO

BACKGROUND/AIM: This phase II trial evaluated the efficacy and safety of neoadjuvant nab-paclitaxel plus cyclophosphamide (CPA) plus trastuzumab (AbraC-HER) in patients with early HER2-positive breast cancer. PATIENTS AND METHODS: This was a single-arm, open-label, single-center prospective phase II study. The primary endpoint was pathological complete response rate (pCR rate). The secondary endpoints were clinical antitumor efficacy and the frequency and severity of adverse events. RESULTS: Fifty-nine patients were enrolled in this study. pCR (ypT0/is ypN0) was achieved in 29 patients (49%). The overall response rate was 88.1% (52/59) in all patients. Dose reductions because of adverse events occurred in 3 patients (5.1%) and relative dose intensity was 98%. Compared to Abra-HER, AbraC-HER induced fewer adverse effects. CONCLUSION: Treatment with nab-paclitaxel plus CPA plus trastuzumab was tolerable and effective with a high pCR rate. This AbraC-HER neoadjuvant therapy may be a feasible new treatment option for patients with early HER2-positive breast cancer.


Assuntos
Albuminas/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Paclitaxel/uso terapêutico , Trastuzumab/uso terapêutico , Adulto , Idoso , Albuminas/efeitos adversos , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Ciclofosfamida/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia Neoadjuvante , Paclitaxel/efeitos adversos , Receptor ErbB-2 , Trastuzumab/efeitos adversos
16.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207035

RESUMO

Breast cancer is the most commonly occurring cancer in women of Western countries and is the leading cause of cancer-related mortality. The breast tumor microenvironment contains immune cells, fibroblasts, adipocytes, mesenchymal stem cells, and extracellular matrix. Among these cells, macrophages or tumor-associated macrophages (TAMs) are the major components of the breast cancer microenvironment. TAMs facilitate metastasis of the breast tumor and are responsible for poor clinical outcomes. High TAM density was also found liable for the poor prognosis of breast cancer. These observations make altering TAM function a potential therapeutic target to treat breast cancer. The present review summarizes the origin of TAMs, mechanisms of macrophage recruitment and polarization in the tumor, and the contributions of TAMs in tumor progression. We have also discussed our current knowledge about TAM-targeted therapies and the roles of miRNAs and exosomes in re-educating TAM function.


Assuntos
Neoplasias da Mama/etiologia , Neoplasias da Mama/metabolismo , Microambiente Tumoral , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Animais , Biomarcadores Tumorais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Comunicação Celular , Progressão da Doença , Suscetibilidade a Doenças , Exossomos/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Imunomodulação , Ativação de Macrófagos/imunologia , MicroRNAs/genética , Metástase Neoplásica , Estadiamento de Neoplasias , Neovascularização Patológica/imunologia , Neovascularização Patológica/metabolismo , Carga Tumoral , Macrófagos Associados a Tumor/patologia
17.
Nat Commun ; 12(1): 4308, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262028

RESUMO

Hypoxia plays a critical role in tumor progression including invasion and metastasis. To determine critical genes regulated by hypoxia that promote invasion and metastasis, we screen fifty hypoxia inducible genes for their effects on invasion. In this study, we identify v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) as a potent regulator of tumor invasion without affecting cell viability. MAFF expression is elevated in metastatic breast cancer patients and is specifically correlated with hypoxic tumors. Combined ChIP- and RNA-sequencing identifies IL11 as a direct transcriptional target of the heterodimer between MAFF and BACH1, which leads to activation of STAT3 signaling. Inhibition of IL11 results in similar levels of metastatic suppression as inhibition of MAFF. This study demonstrates the oncogenic role of MAFF as an activator of the IL11/STAT3 pathways in breast cancer.


Assuntos
Neoplasias da Mama/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Interleucina-11/metabolismo , Fator de Transcrição MafF/metabolismo , Proteínas Nucleares/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Hipóxia Celular , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Fator de Transcrição MafF/genética , Camundongos , Invasividade Neoplásica/patologia , Metástase Neoplásica/patologia , Proteínas Nucleares/genética , Prognóstico , Transdução de Sinais , Transcrição Genética
18.
Medicine (Baltimore) ; 100(22): e26103, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087856

RESUMO

ABSTRACT: Breast cancer (BC) is a malignant tumor originating from cells of the breast. Notably, microRNAs have been recognized as biomarkers of BC metastasis. The present study is designed to evaluate the association between microRNA (miR)-367 expression and BC with the variance of clinicopathologic features and prognosis.Initially, 63 BC patients were allocated in the BC group, while the other 40 healthy volunteers were recruited as the control group. miR-367 expression in the serum of patients and healthy controls was detected using real-time polymerase chain reaction. Furthermore, the relation between miR-367 in serum and clinicopathologic features and prognosis of BC patients was accessed.miR-367 expression in serum of the BC group was evidently lower than that in the control group (all P < .001). Besides, miR-367 underexpression in the BC group was closely associated with the variance in tumor nodes metastasis advanced stage, tumor diameter, and lymph node metastasis of BC (all P < .001). In addition, compared with the control group, poorly expressed miR-367 BC group had short period of disease-free survival and overall survival (all P < .001).Our study demonstrated that miR-367 expression is associated with BC clinicopathologic features and prognosis. This investigation may offer new insight for BC treatment.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , MicroRNAs/biossíntese , Biomarcadores Tumorais , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase em Tempo Real , Carga Tumoral
19.
Am J Clin Oncol ; 44(7): 340-349, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34151896

RESUMO

OBJECTIVE: Ado-trastuzumab emtansine (T-DM1) was recently approved for patients with human epidermal growth factor receptor 2 positive (HER2+) early breast cancer (eBC) with residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment. Cost-effectiveness analysis was conducted to compare T-DM1 versus trastuzumab in the United States. MATERIALS AND METHODS: A Markov cohort-based model tracked clinical and economic outcomes over a lifetime horizon from a US payer perspective. The model included 6 health states: invasive disease-free, nonmetastatic (locoregional) recurrence, remission, first-line and second-line metastatic BC and death. Model state transitions were based on statistical extrapolation of the head-to-head KATHERINE study and published sources. Dosing and treatment duration reflected prescribing information and trials. Costs (2019 US dollars) associated with pharmaceutical treatment (wholesale acquisition costs), health state specific care, adverse events, and end-of-life care were included. Health state utilities were obtained from KATHERINE and published literature. RESULTS: T-DM1 dominated trastuzumab, yielding lower lifetime costs (-$40,271), and higher life-years (2.980) and quality-adjusted life-years (2.336). Results were driven by patients receiving T-DM1 spending less time in more costly downstream health states, as these patients are less likely to experience a recurrence overall, despite having a higher likelihood of metastatic disease (distant recurrence) in the subset of patients who experience recurrence. Probabilistic sensitivity analysis indicated robust results, with 96.7% of 5000 stochastic simulations producing dominance for T-DM1. The most influential variables were related to treatment costs, off treatment utilities, and health state costs. Additional scenario analyses tested a range of model inputs and assumptions, and produced consistent results. CONCLUSION: Relative to trastuzumab, T-DM1 treatment for patients with HER2+ eBC who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment is likely to reduce the overall financial burden of cancer, while simultaneously improving patient outcomes.


Assuntos
Ado-Trastuzumab Emtansina/economia , Ado-Trastuzumab Emtansina/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/economia , Ado-Trastuzumab Emtansina/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/economia , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/economia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Análise Custo-Benefício , Custos de Medicamentos , Feminino , Humanos , Recidiva Local de Neoplasia , Qualidade de Vida , Trastuzumab/efeitos adversos , Trastuzumab/economia , Trastuzumab/uso terapêutico , Estados Unidos
20.
Plast Reconstr Surg ; 148(1): 21-30, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34181601

RESUMO

BACKGROUND: Previous breast surgery does not represent an absolute contraindication for nipple-sparing mastectomy, although it may negatively interfere with surgical outcomes. The aim of the authors' study was to confirm the feasibility of nipple-sparing mastectomy after previous breast surgery, focusing on skin incisions and risk factors, complications, and oncologic outcomes. METHODS: The authors retrospectively identified 368 patients who underwent 387 nipple-sparing mastectomies and reconstruction after previous surgery (quadrantectomy, breast resection, augmentation and reduction mammaplasty, mastopexy) at the European Institute of Oncology from January of 2003 to November of 2017. Patterns of skin incisions (i.e., radial, hemiperiareolar, periareolar, vertical pattern, inframammary fold, Wise-pattern, and round-block) for primary surgery and for mastectomy, type of reconstruction, and radiotherapy have been recorded. The authors collected data regarding early and late complications and further operations (implant change, fat grafting) performed within 2 years to improve cosmetic outcomes. Oncologic follow-up has been reported for in-breast recurrences. RESULTS: Complete and partial nipple-areola complex necrosis occurred, respectively, in 2.8 percent and in 5.4 percent of cases. The authors recorded 5.4 percent failures resulting in implant removal. The analysis of risk factors for complications or for the need for further operations showed no significant association with skin incision for first surgery and mastectomy, use of the same skin incision, previous radiotherapy, or type of primary surgery. Five-year overall survival and disease-free survival were 99.1 and 93.8 percent, respectively. No nipple recurrence was recorded. CONCLUSIONS: The authors' results confirm that nipple-sparing mastectomy can be a safe surgical procedure after previous breast surgery. Surgical planning should be tailored to each patient. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Assuntos
Neoplasias da Mama/terapia , Contraindicações de Procedimentos , Mastectomia Subcutânea/efeitos adversos , Recidiva Local de Neoplasia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Glândulas Mamárias Humanas/patologia , Glândulas Mamárias Humanas/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Mamilos/patologia , Mamilos/cirurgia , Complicações Pós-Operatórias/etiologia , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/estatística & dados numéricos , Reoperação/efeitos adversos , Estudos Retrospectivos , Fatores de Risco
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