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1.
Medicine (Baltimore) ; 99(26): e20681, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590741

RESUMO

Plasma albumin to fibrinogen ratio is involved in human cancer, but its prognostic significance in breast cancer is controversy. In the context of breast invasive ductal carcinoma, this research aims to retrospectively evaluate by preoperative plasma albumin to fibrinogen ratio (AFR) and forecast oncological outcome and recurrence.This retrospective study comprised 230 patients with non-metastatic breast invasive ductal carcinoma who underwent surgery between January 2009 and April 2012 in Fourth Hospital of Hebei Medical University. Patients were categorized base on an optimal value of preoperative plasma fibrinogen (Fib) and albumin. Progression-free and cancer-specific survival were assessed using Kaplan-Meier method. The associations between albumin to fibrinogen ratio and clinical outcomes were assessed with univariate and multivariate analysis. A number of risk factors were used to form nomograms to evaluate survival, and Harrell concordance index (C-index) was used to evaluate the predictive accuracy.Plasma AFR was significantly associated with diminished disease-free survival (DFS) and overall survival (OS). Multivariate analysis revealed that plasma AFR was an independent prognostic indicator for DFS (HR = 1.346; 95% CI: 1.107-1.636; P = .03) and overall survival (OS) (HR = 1.485; 95% CI: 1.106-1.993; P = .008). Two prediction model of 3-, 5-years OS and DFS based on the AFR was developed.Elevated preoperative plasma AFR is an independent prognostic factor for oncological outcomes in patients with breast invasive ductal carcinoma. The formulated nomogram showed superior predictive accuracy for DFS and OS.


Assuntos
Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Fibrinogênio/análise , Nomogramas , Albumina Sérica , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/sangue , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos
2.
Cancer Radiother ; 24(2): 114-119, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32171675

RESUMO

PURPOSE: To evaluate our long-term experience on one-day breast intraoperative radiotherapy (IORT) given as sole radiation treatment to selected patients with breast cancer. METHODS AND MATERIALS: Inclusion criteria of INTRAOBS study (prospective observational study) were: ER+ T1N0 unifocal ductal carcinoma; absence of lymphovascular invasion or of extensive intraductal component (Scarff-Bloom-Richardson grade III and HER2+++ excluded). Two different linacs were used (20Gy/1 fraction): one dedicated electron linac (

Assuntos
Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Segunda Neoplasia Primária , Seleção de Pacientes , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Feminino , Humanos , Cuidados Intraoperatórios/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Satisfação do Paciente , Intervalo Livre de Progressão , Estudos Prospectivos
3.
Cancer Immunol Immunother ; 69(7): 1315-1326, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32198536

RESUMO

In view of the relatively limited efficacy of immunotherapies targeting the PD-1-PD-L1 axis in triple-negative breast cancer (TNBC) and of published reports on tumor-promoting roles of TNFR2+ tumor-infiltrating lymphocytes (TNFR2+ TILs), we determined the incidence of TNFR2+ TILs in TNBC patient tumors, their association with disease outcome and relations with PD-1+ TILs. Using a cohort of treatment-naïve TNBC patients with long follow-up (n = 70), we determined the presence of TNFR2+ TILs and PD-1+ TILs by immunohistochemistry. TILs (≥ 1% of cellular mass) and TNFR2+ TILs (≥ 1% of total TILs) were detected in 96% and 74% of tumors, respectively. The presence of TILs at > 5% of tumor cell mass ("Positive TILs"), as well as of positive TNFR2+ TILs (> 5%), was independently associated with good prognosis, and combination of both parameters demonstrated superior outcome relative to their lower levels. PD1+ TILs (> 5/hot spot) were detected in 63% of patients. High levels of PD-1+ TILs (> 20/hot spot) showed an unfavorable disease outcome, and in their presence, the favorable outcome of positive TNFR2+ TILs was ablated. Thus, TNFR2+ TILs are strongly connected to improved prognosis in TNBC; these findings suggest that TNFR2+ TILs have favorable effects in TNBC patients, unlike the tumor-promoting roles attributed to them in other cancer systems. Overall, our observations propose that the TNFR2+ TIL subset should not be targeted in the course of TNBC therapy; rather, its beneficial impacts may become into power when anti-PD-1 regimens-that may potentiate immune activities-are administered to TNBC patients.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Ductal de Mama/mortalidade , Linfócitos do Interstício Tumoral/imunologia , Receptores Tipo II do Fator de Necrose Tumoral/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal de Mama/imunologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
4.
J Invest Surg ; 33(1): 31-39, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29843540

RESUMO

Background and Objectives: Invasive micropapillary carcinoma (IMPC) of the breast is a rare and aggressive variant of invasive ductal carcinoma characterized by high-grade lymphovascular invasion and high rates of nodal metastasis. The prognostic significance of the micropapillary component (MC) ratio that constitutes this aggressive variation is controversial. In this study, we aimed to investigate the effect of the MC ratio on the prognosis of these patients. Methods: The data of 47 patients with IMPC were retrospectively reviewed. Patients were divided into two groups: MC ratio of 10-75% (Group 1) and greater than 75% (Group 2). The demographic characteristics of the patients, histopathologic features of the tumors, and survival rates were compared. Results: We detected no significant difference in demographic characteristics between groups 1 and 2 (p = 0.21). No significant difference was detected in terms of tumor diameter, lymph node metastasis, lymphovascular invasion, histologic grade, multicentricity, local recurrence, distant metastasis, and overall survival. Conclusion: In the micropapillary subgroup of invasive ductal carcinoma, although positive receptor characteristics are directly proportional to the increase in MC ratio, recurrence and survival rates are not affected by micropapillary component level.


Assuntos
Neoplasias da Mama/mortalidade , Mama/patologia , Carcinoma Ductal de Mama/mortalidade , Mastectomia , Recidiva Local de Neoplasia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Mama/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Papilar , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
5.
BMC Cancer ; 19(1): 1167, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791269

RESUMO

BACKGROUND: Circulating tumor cells (CTCs) are associated with breast cancer prognosis. Research is limited regarding the role of circulating cancer stem-like cells (cCSCs) considering the treatment response and survival among patients with metastatic breast cancer. Accordingly, we performed this prospective study to clarify the prognostic significance of baseline cCSCs for metastatic breast cancer in terms of first-line chemotherapy. METHODS: Between April 2014 and January 2016, we prospectively enrolled 48 patients with stage IV breast invasive ductal carcinoma who underwent first-line chemotherapy. We identified and analyzed CTCs and cCSCs by using a protocol based on negative selection and flow cytometry before chemotherapy. CTCs were identified as EpCAM+Hoechst+CD45- cells and cCSCs as CD133+EpCAM+Hoechst+CD45- cells. cCSCs were expressed as a percentage of CTCs. The associations between CTCs, cCSCs, and the clinicopathological variables that were predictive of the treatment response and survival outcome were analyzed using univariate and multivariate analyses. RESULTS: We identified CTCs in all the enrolled patients, with a median number of 33.9/mL CTCs. CSCs were isolated in 97.9% of the patients; the median percentage of cCSCs was 14.7%. A high baseline level of cCSCs was correlated with an inferior tumor response rate (54.2% vs. 95.8%, p < 0.001), overall survival (OS; median: 27.7 months vs. not reached, p < 0.001), and progression-free survival (PFS; median: 5.7 vs. 18.0 months, p < 0.001). Multivariate analysis revealed that along with other clinical variables, baseline cCSCs remained an independent prognostic factor for OS and PFS. CONCLUSIONS: Baseline cCSCs predict the treatment response as well as survival in patients with metastatic breast cancer undergoing first-line chemotherapy. Therefore, the measurement of cCSCs may assist in identifying early cancer treatment response and prognosis.


Assuntos
Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Células Neoplásicas Circulantes/patologia , Células-Tronco Neoplásicas/patologia , Antígeno AC133/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/patologia , Contagem de Células , Feminino , Humanos , Biópsia Líquida , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/imunologia , Células-Tronco Neoplásicas/imunologia , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento
6.
Rev Med Chil ; 147(5): 557-567, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31859887

RESUMO

BACKGROUND: Breast cancer (BC) is the most common malignancy in women. AIM: To assess the impact of HER2 status on axillary lymph node (ALN) involvement in patients with invasive ductal carcinoma of no special type (IDC-NST) both at diagnosis and during the 4-year postoperative period. PATIENTS AND METHODS: We retrospectively included 375 women with an early clinical stage of non-luminal IDC-NST who between 2007 and 2013 underwent breast surgery at a clinical hospital. They were divided into phenotype-based groups: HR+HER2-, HR+HER2+, HR-HER2+ and HR-HER2-. Only patients with sentinel lymph node (SLN) macrometastases underwent ALN dissection. If > 3 ALNs were positive, radiotherapy was delivered. All patients were treated with chemotherapy, HER2+ BC patients received trastuzumab, and hormone receptor (HR)-positive BC patients received hormonal therapy. RESULTS: Larger tumor size, higher grade, HR+, HER2+ status, and lymphovascular invasion (LVI) were predictive for ALN metastases at diagnosis. The poorest overall, disease-free, and distant recurrence-free survival (OS, DFS, DRFS) were found in the HR-HER2- group, while the poorest locoregional recurrence-free survival (LRFS) was observed in HR-HER2+ and HR-HER2- groups. HER2 status was not predictor of survival. CONCLUSIONS: HER2+ status was predictive for ALN involvement at diagnosis but had no effect on 4-year LRFS in these patients.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Receptor ErbB-2/análise , Linfonodo Sentinela/patologia , Adulto , Idoso , Axila , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Antígeno Ki-67/análise , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Retrospectivos , Estatísticas não Paramétricas , Fatores de Tempo , Carga Tumoral
7.
Radiat Oncol ; 14(1): 234, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31864391

RESUMO

BACKGROUND: To update the clinical outcome of an elderly women cohort with early breast cancer who underwent accelerated partial breast irradiation (APBI) based on a post-operative single fraction of multicatheter interstitial high dose-rate brachytherapy (MIB). MATERIAL AND METHODS: A single institution retrospective cohort study was performed focusing on elderly patients (≥ 65 years old) presenting a low-risk breast carcinoma treated by lumpectomy plus axillary evaluation followed by MIB APBI. A single fraction of 16 Gy was prescribed on the 100% isodose. Clinical outcome at 5 years was reported based on local relapse free survival (LRFS), specific survival (SS) and overall survival (OS). Late toxicity was evaluated. Cosmetic results were evaluated clinically by the physician. RESULTS: Between January 2012 and August 2015, 48 women (51 lesions) were treated. Median age was 77.7 years (range: 65-92) with a median tumor size of 12 mm (range: 3-32). Five patients (pts) presented an axillary lymph node involvement (4 Nmic, 1 N1). Invasive ductal carcinoma was the most frequent histology type (86.3%). With a median follow-up of 64 months (range: 56-71), no local relapse occurred while 1 pt. developed an axillary relapse (2.1%). No Grade 3 or higher late toxicity was observed while 16 late toxicities occurred (G1: 14 events [87.5%) mainly G1 breast fibrosis). The rate of excellent cosmetic outcome was 76.4%. CONCLUSION: We confirmed the safety of the process and remained encouraging clinical outcome of a post-operative single fraction of MIB ABPI in the elderly. This approach leads to consider a very APBI as an attractive alternative to intra-operative radiation therapy while all the patients will be good candidates for APBI in regards to the post-operative pathological report.


Assuntos
Braquiterapia/mortalidade , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Lobular/mortalidade , Recidiva Local de Neoplasia/mortalidade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Lobular/patologia , Carcinoma Lobular/radioterapia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Fracionamento da Dose de Radiação , Feminino , Humanos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo
8.
Oncol Rep ; 42(6): 2550-2560, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638259

RESUMO

Breast cancer (BC) is the most common invasive cancer in women, and it imposes a heavy burden on patients. microRNAs (miRNAs/miRs) have been found to play an important role in the development of tumors, but their role in the malignant progression of BC is unclear. In the present study, the expression level of miR­425­5p was examined in patients with BC, and its association with prognosis was investigated. In vitro experiments were performed to examine role of miR­425­5p in the development of BC cells. A downstream target gene of miR­425­5p was predicted using a miRNA target prediction tool and validated with a luciferase reporter assay. It was found that miR­425­5p expression was increased in BC tissues and cell lines, and was associated with tumor size, clinical stage, lymph node metastasis, distant metastasis and poor overall survival in patients with BC. Knockdown of miR­425­5p in BC cell lines inhibited proliferation and migration. PTEN was identified as a downstream target gene of miR­425­5p. Overexpression of PTEN was demonstrated to partially inhibit the promotional effect of miR­425­5p on cell proliferation and migration. Taken together, miR­425­5p is associated with poor prognosis, and promotes cell proliferation and migration via PTEN. Thus, miR­425­5p may serve as a therapeutic and prognostic marker for BC.


Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Intervalo Livre de Doença , Feminino , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/genética , Metástase Linfática/patologia , Células MCF-7 , Mastectomia , MicroRNAs/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
9.
Int J Surg ; 71: 91-99, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31546033

RESUMO

BACKGROUND: Previous studies have indicated that there may be a difference in tumor biology between intraductal papillary mucinous carcinoma (IPMC) and pancreatic ductal adenocarcinoma (PDAC). However, the data are still controversial. The aim of this systematic review and meta-analysis was to summarize and compare the outcome of IPMC and PDAC after surgical resection. METHODS: Studies comparing IPMC and PDAC were identified using Medline and Embase search engines. Primary outcomes of interest were survival and recurrence. Secondary outcomes were clinicopathological characteristics. Meta-analysis of data was conducted using a random-effects model. RESULTS: A total of 14 studies were included. Pooled analysis revealed an improved 5-year overall survival (OS) for IPMC compared to PDAC (OR 0.23, 95% CI 0.09-0.56). Both colloid and tubular IPMC showed improved 5-year OS compared to PDAC (OR 0.12, 95% CI 0.05-0.25 and OR 0.38, 95% CI 0.26-0.54, respectively). Median survival time ranged from 21 to 58 months in the IPMC group compared to 12-23 months in the PDAC group. No meta-analysis could be performed on recurrence or on time-to-event data. Descriptive data showed no survival difference for higher TNM stages. IPMC was more often found at a TNM-stage of 1 (OR 4.40, 95% CI 2.71-7.15) and had lower rates of lymph node spread (OR 0.43, 95% CI 0.32-0.57). CONCLUSION: Available data suggest that IPMC has a more indolent course with a better 5-year OS compared to PDAC. The histopathological features are less aggressive in IPMC. The reason may be earlier detection. However, for IPMC with higher TNM stages the survival seems to be similar to that of PDAC.


Assuntos
Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Papilar/patologia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Papilar/mortalidade , Idoso , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal Pancreático/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Taxa de Sobrevida
10.
Zhonghua Zhong Liu Za Zhi ; 41(9): 686-692, 2019 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-31550859

RESUMO

Objective: To analyze the clinicopathological features and prognosis of breast invasive ductal carcinoma patients receiving radical mastectomy according to the primary tumor location. Methods: From January 2008 to December 2008, 993 patients with breast invasive ductal carcinoma received radical mastectomy in Tianjin Medical University Cancer Institute and Hospital. Patients were grouped according to the primary tumor location when breast cancer was diagnosed. The clinicopathological characteristics and follow-up information of them was collected and analyzed retrospectively. Results: Of the 993 patients, primary tumor located in the upper-outer quadrant (UOQ) in 556 patients (56.0%), the lower-outer quadrant (LOQ) in 97 (9.8%), the central portion in 99 (10.0%), the upper-inner quadrant (UIQ) in 186 (18.7%), and the lower-inner quadrant (LIQ) in 55 (5.5%). Patients in the central portion tended to have larger tumors, and more patients in the upper-inner quadrant received endocrine therapy. The estimated 5-year disease-free survival (DFS) rates of patients with primary lesion in the UOQ, LOQ, central portion, UIQ and LIQ were 90.3%, 88.7%, 79.8%, 86.0% and 72.7%, respectively, with significant differences (P<0.001). The 5-year overall survival (OS) rates were 97.5%, 96.9%, 90.9%, 94.1% and 87.3%, respectively, with significant differences (P<0.001). Multivariate analysis showed that 5-year recurrence and metastasis risks were significantly increased in patients with primary lesion in the central portion, UIQ and LIQ compared to other groups (P<0.001), and 5-year mortality risks were increased in these three groups (P=0.002). Conclusion: Primary lesion located in central portion and inner quadrant is an independent adverse prognostic factor for patients with breast invasive ductal carcinoma patients receiving radical mastectomy.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Mastectomia , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/cirurgia , Humanos , Linfonodos , Metástase Linfática/patologia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
11.
Surg Oncol ; 30: 141-146, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31500779

RESUMO

BACKGROUND: The oncologic benefit of upfront re-excision of involved margins after breast-conserving surgery in the context of current multimodal clinical management of breast cancer is unclear. The aim of the present study was to assess the 5-years locoregional recurrence (LRR)-free and distant metastases (DM)-free survival probabilities in patients not undergoing re-excision of positive margins after lumpectomy for breast cancer. METHODS: A cohort of 104 patients with positive margins not undergoing re-excision was matched by propensity score with a cohort of 2006 control patients with clear margins after breast-conserving surgery, treated between 2008 and 2018. A multivariate survival analysis was performed accounting for all variables related to LRR and DM, including adjuvant treatments. RESULTS: After adjusting for potential confounders, avoiding to re-excise a positive margin after lumpectomy had no effect on 5-years LRR-free survival probability (HR 0.98, 95%CI 0.36-2.67, p = 0.96) or 5-years DM-free survival probability (HR 0.37, 95%CI 0.08-1.61, p = 0.18). No correlation was found between occurrence of LRR and number of involved margins (HR 1.28, 95%CI 0.10-12.4, Log-rank p = 0.83), or extension of infiltrating disease (HR 1.21, 95%CI 0.20-7.40, Log-rank p = 0.83), but a trend toward higher LRR probability was found for invasive ductal (HR 6.92, 95%CI 0.7-68.8, Log-rank p = 0.10) and invasive lobular cancer (HR 12.95, 95%CI 0.79-213.6, Log-rank p = 0.07) on positive margins. CONCLUSIONS: In the era of multimodal treatment of breast cancer and accurate strategies to reduce the probability of residual disease in the post-lumpectomy cavity, re-excision of positive margins might be omitted in selected patients with low-risk breast cancers.


Assuntos
Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Intraductal não Infiltrante/mortalidade , Carcinoma Lobular/mortalidade , Margens de Excisão , Mastectomia Segmentar/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/secundário , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Lobular/secundário , Carcinoma Lobular/cirurgia , Feminino , Seguimentos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Prospectivos , Reoperação , Estudos Retrospectivos , Taxa de Sobrevida
12.
Breast J ; 25(6): 1171-1176, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31321854

RESUMO

Invasive micropapillary carcinoma (IMPC) is an uncommon variant of breast cancer. Previous studies demonstrated this subtype is often hormone receptor (HR)-positive, resulting in survival outcomes similar to invasive ductal carcinoma. However, many of these studies were conducted prior to HER2 testing availability. We aim to determine the impact of molecular marker status (including HER2 status) on IMPC survival outcomes. The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven IMPC from 2007 to 2012. Only patients with known HR and HER2 status were included. Cox multivariate regression was used to determine prognostic factors. In total, 865 patients were included; median follow-up was 2.5 years. Overall, 651 patients (75.3%) had HR + HER2- disease, 128 (14.8%) had HR + HER2+ disease, 41 (4.7%) had HR-HER2 + disease, and 45 (5.2%) had triple negative disease. Patients with triple negative disease were more likely to have poorly differentiated histology (66.7%), lymphovascular invasion (73.3%), stage 3 disease (37.8%), undergone mastectomy (68.9%), and positive surgical margins (15.6%). On Cox multivariate regression, those with triple negative disease had worse overall survival (hazard ratio [HR] 7.28, P < 0.001). Other adverse prognostic factors included African-American descent (HR 2.24, P = 0.018), comorbidity score of 1 (HR 2.50, P = 0.011), comorbidity score ≥2 (HR 3.27, P = 0.06), and ≥3 positive lymph nodes (HR 3.23, P = 0.007). Similar to invasive ductal carcinoma, triple negative disease in IMPC results in worse survival outcomes. This is the largest and first study to characterize molecular status (including HER2 status) in patients with IMPC and its impact on survival outcomes.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Papilar/mortalidade , Carcinoma Papilar/patologia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Receptor ErbB-2 , Sistema de Registros , Estudos Retrospectivos , Análise de Sobrevida
13.
Breast ; 47: 93-101, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31362135

RESUMO

OBJECTIVES: The aim of this retrospective study is to compare surgical margins, reoperation rates and local recurrences after breast conserving surgery (BCS) using radioguided occult lesion localization (ROLL) or radioactive seed localization (RSL). MATERIALS AND METHODS: We reviewed 744 consecutive patients with impalpable primary invasive breast cancer who underwent BCS at Helsinki University Hospital between 2010 and 2012. ROLL was used in our unit until October 31st, 2011; from November 1st we changed localization method to RSL. RESULTS: 318 patients underwent ROLL and 426 RSL. Patients in the RSL group had more often multifocal (p = 0.013) tumours. No statistically significant differences were found regarding tumour size, specimen weight, histology or grade of tumours or lymph node status. 42 (5.6%) patients were reoperated because of insufficient margins, 13 (4.1%) in the ROLL group and 29 (6.8%) in the RSL group. The reoperation rate was not different between the groups either in the univariable analysis (p = 0.112) or in the multivariable binary logistic regression analysis (p = 0.204). Risk factors for reoperations were multifocality of the tumour (p < 0.001), extensive intraductal component (p < 0.001), larger tumour size (p = 0.011), and smaller specimen weight (p = 0.014). The median follow-up time in the ROLL group was 81 (8-94) months and 64 (3-73) months in the RSL group. The five-year local recurrence-free survival (LRFS) estimates for ROLL and RSL groups were 98.0% and 99.4%, respectively (log-rank test, p = 0.323). CONCLUSION: Reoperation rates and LRFS were comparable for ROLL and RSL in patients with impalpable breast cancer treated with BCS.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Margens de Excisão , Mastectomia Segmentar/métodos , Recidiva Local de Neoplasia/patologia , Ultrassonografia Mamária/métodos , Adulto , Idoso , Biópsia com Agulha de Grande Calibre/métodos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/mortalidade , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Finlândia , Hospitais Universitários , Humanos , Mastectomia Segmentar/efeitos adversos , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Palpação , Prognóstico , Cintilografia/métodos , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida
14.
Ann Surg Oncol ; 26(12): 3892-3901, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31350646

RESUMO

BACKGROUND: The impact of locoregional radiotherapy (RT) after neoadjuvant chemotherapy (NACT) and mastectomy in breast cancer patients is currently unclear. Several publications have suggested that patients with a favorable response to NACT might not benefit from RT after mastectomy. METHODS: A retrospective analysis of three prospective randomized NACT trials was performed. Information on the use of RT was available for 817 breast cancer patients with non-inflammatory breast cancer who underwent mastectomy after NACT within the GeparTrio, GeparQuattro, and GeparQuinto-trials. RT was administered to 676 of these patients (82.7%). RESULTS: The 5-year cumulative incidence of locoregional recurrence (LRR) was 15.2% (95% confidence interval [CI] 9.0-22.8%) in patients treated without RT and 11.3% in patients treated with RT (95% CI 8.7-14.3%). In the multivariate analysis, RT was associated with a lower risk of LRR (hazard ratio 0.51, 95% CI 0.27-1.0; p = 0.05). This effect was shown especially in patients with cT3/4 tumors, as well as in patients who were cN+ before neoadjuvant therapy, including those who converted to ypN0 after neoadjuvant therapy. In the bivariate analysis, disease-free survival was significantly worse in patients who received RT, however this was not confirmed in the multivariate analysis. CONCLUSIONS: Our results suggest that RT reduces the LRR rates in breast cancer patients who receive a mastectomy after NACT without an improvement in DFS. Prospective randomized controlled trials such as the National Surgical Adjuvant Breast and Bowel Project B-51/RTOG 1304 trial will analyze whether RT has any benefit in patients who have a favorable response after NACT.


Assuntos
Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Lobular/mortalidade , Mastectomia/mortalidade , Terapia Neoadjuvante/mortalidade , Recidiva Local de Neoplasia/mortalidade , Radioterapia/mortalidade , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/patologia , Carcinoma Lobular/terapia , Terapia Combinada , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Incidência , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
15.
Am J Clin Pathol ; 152(5): 656-665, 2019 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-31305879

RESUMO

OBJECTIVES: Tumor-infiltrating lymphocytes (TILs) have recently emerged as a prognostic factor in breast cancer. In our previous study, we proposed that tumor stroma should also be considered in the calculation of TILs and we introduced tumor infiltration lymphocyte volume (TILV) in triple-negative breast cancer. METHODS: We assessed the disease-free survival predictive value of TILV in all subtypes of invasive breast carcinoma and compared the predictive value of TILV with TILs. Differences between disease-free survival curves were determined by using the log-rank test, and Kaplan-Meier survival plots were generated for both groups. RESULTS: TILV was significantly correlated with disease-free survival in both invasive ductal carcinoma (P = .03) and all subtypes of invasive breast carcinoma (P = .043), whereas TILs failed to show a statistical significance. CONCLUSIONS: Tumor-stroma ratio needs to be considered in estimation of tumor immunity, and TILV adds more predictive power to TILs.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Linfócitos do Interstício Tumoral/patologia , Células Estromais/patologia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/mortalidade , Carcinoma Lobular/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Reprodutibilidade dos Testes , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia
16.
J Pak Med Assoc ; 69(7): 976-980, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31308566

RESUMO

OBJECTIVE: To explore and better understand clinic pathological details of breast cancer patients and analyse their survival rate among different treatment groups. Methods: The prospective cohort, multi-centric study was conducted from September, 2014, to February, 2018, at five hospitals in Rawalpindi and Islamabad, Pakistan, and comprised histo-pathologically confirmed breast cancer cases. Patient characteristics and medical history were collected using a detailed questionnaire. All the subjects were followed up, and information regarding their current health and treatment status was collected. Data was analysed using SPSS 24. RESULTS: There were 347 subjects with a mean age of 44.3±12.2 years and body mass index of 27.9±4.0 kg/m2. Younger age, increased body mass index, consanguinity and family history were major contributing factors in breast cancer development (p<0.05). Overall, 267(77%) had invasive ductal carcinoma and Grade II tumour 234(67%) was more frequent. A total of 221(64%) cases had positive lymph nodes and 97(28%) had metastasis to different body organs. Overall survival analysis showed statistically significant role (p<0.0001) of all treatment options. CONCLUSIONS: Combination of different treatments can provide more promising health outcomes in breast cancer cases.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Mastectomia/métodos , Radioterapia/métodos , Adulto , Fatores Etários , Índice de Massa Corporal , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Estudos de Coortes , Terapia Combinada , Consanguinidade , Feminino , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Paquistão/epidemiologia , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Taxa de Sobrevida
17.
Ann Surg Oncol ; 26(10): 3260-3268, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31342356

RESUMO

BACKGROUND: Surgery after neoadjuvant chemotherapy (NCT) is an accepted treatment approach for locally advanced and some early-stage breast cancers, even for patients with a clinical complete response (cCR) after NCT. This study sought to evaluate the survival outcomes for patients with cCR to NCT who did not undergo surgery. METHODS: The National Cancer Data Base (NCDB) was used to identify 93,417 women age 18 years or older with a diagnosis of invasive breast cancer who received NCT between 2010 and 2015. The study identified 350 women with cT1-4, N0-3, and M0 tumors who underwent NCT and did not have surgery. A matched surgical cohort was extracted from the NCDB, and overall survival (OS) was compared between the surgical and nonsurgical patients after NCT. RESULTS: Of the 350 NCT patients who did not undergo surgery, 45 (12.9%) had cCR, 51 (14.6%) had a partial response, 241 (68.9%) had a response but whether complete or partial was not recorded, and 13 (3.7%) had no response/progression. The 5-year OS was better in the cCR group than in the no-cCR group (96.8% vs 69.8%; p = 0.004). A 5-year OS analysis of the cCR patients without surgery (n = 45; median follow-up period, 37 months) compared with the patients with a pathologic complete response who underwent surgery (n = 3938; median follow-up period, 43 months) showed no statistically significant difference (96.8% vs 92.5%, respectively; p = 0.15). CONCLUSION: This retrospective cohort study demonstrated that active surveillance or de-escalation therapy may be an option for patients who achieve cCR. Prospective studies are underway to determine whether a subgroup of patients may forgo surgery in the setting of cCR after NCT.


Assuntos
Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Lobular/mortalidade , Quimioterapia Adjuvante/mortalidade , Mastectomia/mortalidade , Terapia Neoadjuvante/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
18.
J Biosci ; 44(2)2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31180050

RESUMO

To investigate the source of serum exosomal HOTAIR, to uncover the diagnostic and prognostic values of serum exosomal HOTAIR, and to discern the expression of serum exosomal HOTAIR between neoadjuvant chemotherapy and response to tamoxifen therapy. Samples were collected from the Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan. Exosomes were isolated from serum, cell culture medium and tumor tissues. We used transmission electron microscopy and western immunoblotting assay to characterize exosomes, and real-time PCR (qPCR) to assess HOTAIR expression. Neoadjuvant chemotherapy and tamoxifen therapy were carried out according to established guidelines. Breast cancer patients expressed higher serum exosomal HOTAIR than did healthy individuals (P\0.001). Serum exosomal HOTAIR levels 3 months after surgery were markedly decreased compared with levels before surgery (P\0.001), and the expression level of exosomal HOTAIR in cell culture medium increased with time in both breast cancer cell lines (72 h greater than 48 h greater than 24 h, 48 h vs 24 h [ [P less than 0.05]; 72 h vs 24 h [P less than 0.01]. Expression of serum exosomal HOTAIR in nude mice was notably greater than in the mock control group (P less than 0.001). The results of the ROC analysis revealed an AUC for serum exosomal HOTAIR of 0.9178 with a 95% CI of 0.8407-1.017 (P less than 0.01). The AUC for the CA15-3 cell line was 0.7378 (95% CI, 0.5585-0.9170; P = 0.03). High expression of exosomal HOTAIR led to a worse disease-free survival (P = 0.0481) and overall survival (P = 0.0463). In the high-expression chemotherapy group, six patients achieved a partial response (PR) and eight demonstrated stable disease (SD) and nine patients achieved PR and two SD in the low-expression group (P = 0.048). In the low-expression tamoxifen group, one patient had a recurrence of breast cancer and another 10 patients exhibited no recurrence, while six showed recurrence, and seven had none in the highexpression group (P = 0.035). We isolated exosomes successfully, and demonstrated that serum exosomal HOTAIR originated from primary breast cancer tissue. We conclude that serum exosomal HOTAIR exhibits the potential to be a diagnostic and prognostic biomarker. High expression of serum exosomal HOTAIR was also correlated with poor neoadjuvant chemotherapy and response to tamoxifen therapy.


Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/genética , Exossomos/química , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Adulto , Idoso , Animais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/mortalidade , Carcinoma Lobular/sangue , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/mortalidade , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Exossomos/metabolismo , Feminino , Humanos , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Análise de Sobrevida , Tamoxifeno/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Ann Surg Oncol ; 26(12): 3846-3855, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31222687

RESUMO

BACKGROUND: Recent trials have demonstrated the feasibility of sentinel lymph node biopsy (SLNB) for cN1 breast cancer patients after neoadjuvant chemotherapy (NAC). This study evaluated the technical outcomes of SLNB by residual nodal disease volume. METHODS: From a prospective database, cT1-3 cN1 patients receiving NAC and surgery from 2016 to 2017 were identified. Performance measures of post-NAC physical exam and imaging-based axillary assessment were compared. For the patients who converted to cN0 and underwent SLNB, adequate mapping (defined as ≥ 3 SLN) and the false-negative rate (FNR) of intraoperative SLN evaluation were assessed by residual nodal disease volume (ypN1-3 vs ypN0[i+]/ypN1mi vs ypN0). RESULTS: Of 156 cT1-3 cN1 patients, 96 converted to cN0 and underwent SLNB. Adequate mapping was achieved for 64 patients (66.7%) and was not associated with nodal volume (p = 0.12). The FNR of the intraoperative SLN evaluation was 37.8%, and smaller nodal volume was associated with FNR (p < 0.01). Of 36 patients (37.5%) who achieved an axillary pathologic complete response, 24 (66.7%) had three or more negative SLNs and were safely spared axillary lymph node dissection (ALND). The positive predictive values of physical exam versus imaging-based post-NAC nodal assessment were respectively 88% and 69.8%. CONCLUSIONS: This study showed SLNB to be an effective tool for minimizing axillary surgery in cN1 patients treated with NAC. However, important technical limitations exist, such as inability to identify three SLNs in more than two-thirds of patients and high-false negative rates for intraoperative SLN evaluation, particularly for patients with small residual nodal volumes. Preoperative counseling should include realistic assessment of the potential need for ALND in this population.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Lobular/mortalidade , Terapia Neoadjuvante/mortalidade , Neoplasia Residual/mortalidade , Biópsia de Linfonodo Sentinela/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/secundário , Carcinoma Lobular/cirurgia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/patologia , Neoplasia Residual/cirurgia , Prognóstico , Estudos Prospectivos , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Taxa de Sobrevida
20.
Breast Cancer Res Treat ; 177(1): 17-27, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31134489

RESUMO

PURPOSE: Ductal carcinoma in situ (DCIS) of the breast is often regarded as a non-obligate precursor to invasive breast carcinoma but current diagnostic tools are unable to accurately predict the invasive potential of DCIS. Infiltration of immune cells into the tumour and its microenvironment is often an early event at the site of tumourigenesis. These immune infiltrates may be potential predictive and/or prognostic biomarkers for DCIS. This review aims to discuss recent findings pertaining to the potential prognostic significance of immune infiltrates as well as their evaluation in DCIS. METHODS: A literature search on PubMed was conducted up to 28th January 2019. Search terms used were "DCIS", "ductal carcinoma in situ", "immune", "immunology", "TIL", "TIL assessment", and "tumour-infiltrating lymphocyte". Search filters for "Most Recent" and "English" were applied. Information from published papers related to the research topic were synthesised and summarised for this review. RESULTS: Studies have revealed that immune infiltrates play a role in the biology and microenvironment of DCIS, as well as treatment response. There is currently no consensus on the evaluation of TILs in DCIS for clinical application. CONCLUSIONS: This review highlights the recent findings on the potential influence and prognostic value of immunological processes on DCIS progression, as well as the evaluation of TILs in DCIS. Further characterisation of the immune milieu of DCIS is recommended to better understand the immune response in DCIS progression and recurrence.


Assuntos
Neoplasias da Mama/imunologia , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/imunologia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Intraductal não Infiltrante/imunologia , Carcinoma Intraductal não Infiltrante/mortalidade , Linfócitos do Interstício Tumoral/imunologia , Microambiente Tumoral/imunologia , Animais , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Subpopulações de Linfócitos B/patologia , Biomarcadores , Biomarcadores Tumorais , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Citotoxicidade Imunológica , Progressão da Doença , Estrogênios/metabolismo , Feminino , Humanos , Imunofenotipagem , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Prognóstico , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia
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