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As the malignancy with the highest global incidence, breast cancer represents a significant threat to women's health. Recent advances have shed light on the importance of mitochondrial function in cancer, particularly in metabolic reprogramming within tumors. Recognizing this, we developed a novel risk signature based on mitochondrial-related genes to improve prognosis prediction and risk stratification in breast cancer patients. In this study, transcriptome data and clinical features of breast cancer samples were extracted from two sources: the TCGA, serving as the training set, and the METABRIC, used as the independent validation set. We developed the signature using LASSO-Cox regression and assessed its prognostic efficacy via ROC curves. Furthermore, the signature was integrated with clinical features to create a Nomogram model, whose accuracy was validated through clinical calibration curves and decision curve analysis. To further elucidate prognostic variations between high and low-risk groups, we conducted functional enrichment and immune infiltration analyses. Additionally, the study encompassed a comparison of mutation landscapes and drug sensitivity, providing a comprehensive understanding of the differing characteristics in these groups. Conclusively, we established a risk signature comprising 8 mitochondrial-related genes-ACSL1, ALDH2, MTHFD2, MRPL13, TP53AIP1, SLC1A1, ME3, and BCL2A1. This signature was identified as an independent risk predictor for breast cancer patient survival, exhibiting a significant high hazard ratio (HR = 3.028, 95%CI 2.038-4.499, P < 0.001). Patients in the low-risk group showed a more favorable prognosis, with enhanced immune infiltration, distinct mutation landscapes, and greater sensitivity to anti-tumor drugs. In contrast, the high-risk group exhibited an adverse trend in these aspects. This risk signature represents a novel and effective prognostic indicator, suggesting valuable insights for patient stratification in breast cancer.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Prognóstico , Genes Mitocondriais , Mitocôndrias/genética , Medição de Risco , Aldeído-Desidrogenase MitocondrialRESUMO
AIM: We constructed a multicentre cohort in China to analyse the differences in clinical characteristics, treatment strategies and prognoses between breast neuroendocrine carcinoma (NEC) and invasive ductal carcinoma (IDC) of the breast. METHODS: All patients with early-stage breast cancer who attended three hospitals in Beijing from 2000 to 2018 were included in the study. We used propensity score matching to make a 1:3 match between NEC and IDC. RESULTS: After propensity score matching, 153 patients with IDC and 51 patients with NEC were analysed. Multivariate Cox regression showed that compared to patients with IDC, patients with NEC had a worse disease-free survival (HR = 2.94, 95% CI: 1.69-5.12, p < 0.001). CONCLUSION: NEC patients have a worse disease-free survival than IDC patients.
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Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Neuroendócrino , Humanos , Feminino , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/terapia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Prognóstico , China/epidemiologia , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/epidemiologia , Carcinoma Neuroendócrino/terapiaRESUMO
BACKGROUND: Primary neuroendocrine breast carcinomas (NEBCs) are an extremely rare and underrecognized subtype of mammalian carcinoma. The prognostic factors for NEBCs remain controversial. METHODS: In this multicenter retrospective study, the prognostic factors for patients with primary NEBCs who underwent surgery and had a pathologically confirmed diagnosis of neuroendocrine carcinoma in China and the United States were examined. The endpoints were disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 51 Chinese patients and 98 US patients were included. In the Chinese cohort, tumor grade and Ki-67 levels were prognostic factors for DFS in univariate analysis (hazard ratio [HR] = 5.11 [1.67-15.60], p = 0.004; HR = 57.70 [6.36-523.40], p < 0.001, respectively) and multivariate analysis (HR = 100.52 [1.33-7570.21], p = 0.037; HR = 31.47 [1.05-945.82], p = 0.047, respectively). In the US cohort, age was an important prognostic factor for OS in univariate analysis (HR = 1.09 [1.04-1.15], p = 0.001). The random effects model for the combined cohorts revealed age and positive expression of estrogen receptor (ER) as potential prognostic factors for OS (HR = 1.08 [1.01-1.14], p = 0.015; HR = 0.10 [0.02-0.44], p = 0.003, respectively). CONCLUSIONS: Tumor grade and Ki-67 levels are important prognostic factors for DFS of patients with primary NEBCs. Age and ER status are important prognostic factors for OS of patients with primary NEBCs.
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Neoplasias da Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Antígeno Ki-67/metabolismo , Prognóstico , Receptor ErbB-2/metabolismo , Estudos RetrospectivosRESUMO
BACKGROUND: Breast cancer is currently the most common female malignancy in China. However, the clinical features and overall prognosis of young women diagnosed with this malignancy remain unclear. This study aimed to describe the clinicopathological characteristics of young patients (≤34 years of age) with breast cancer and explore the current treatment approaches used in China. METHODS: This was a hospital-based, multicenter, retrospective study of women with breast cancer across seven Chinese hospitals from 1999 to 2008. A total of 295 young (≤34 years of age) patients (research group) and 2,119 women aged 35 to 49 years (control group) were included in the study. Patient epidemiology, pre-operative examinations, clinical pathology, and treatment were analyzed. RESULTS: The percentage of young patients with breast cancer in the study group was 7.01%. These young women had a lower body mass index (BMI), a higher level of education, a lower number of previous births, and a lower history of breastfeeding than the control group (P<0.05). Increasingly, pre-operative use of ultrasound and magnetic resonance imaging are being used to diagnose breast cancer in young women in China. In young women with breast cancer, breast cancer not otherwise specified (NOS) was the primary pathology. The carcinoma in young women was more prone to lymph node metastasis, showed less progesterone receptor (PR) expression, and was more advanced than observed in the control group (P<0.05). We found that the number of young breast cancer patients undergoing breast-conserving surgery in China is increasing. CONCLUSIONS: Young breast cancer patients display unique clinicopathological features, including tumors of a higher grade than those aged 35 years or older. As breast cancer is more aggressive in younger women, prevention and early diagnosis are critical, and new policies should be developed in line with these findings.
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PURPOSE: To evaluate the effect of adjuvant chemotherapy on improving the prognosis of patients with stage I triple-negative breast cancer (TNBC). METHODS: TNBC patients diagnosed in the SEER 18 database from 2010 to 2015 were included. Kaplan-Meier plots and log-rank tests were used to compare the differences in breast cancer-specific survival (BCSS) and overall survival (OS) between subgroups of variables. A Cox proportional hazard model was used to determine the prognostic factors affecting BCSS and OS. RESULTS: A total of 9256 patients were enrolled in this study. Among these patients, 380 died from breast cancer, and 703 died from all causes. Patients who received chemotherapy had significantly better BCSS and OS than those who did not receive chemotherapy for stage T1cN0M0 (BCSS, hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.51-0.90; OS, HR = 0.54, 95% CI 0.44-0.67) and stage IB (BCSS, HR = 0.39, 95% CI 0.16-0.95; OS, HR = 0.41, 95% CI 0.19-0.87) disease. Patients who received chemotherapy did not have significantly better BCSS or OS than those who did not receive chemotherapy for stage T1aN0M0 or T1bN0M0 disease. The patients who received chemotherapy in the poorly differentiated and undifferentiated groups had better BCSS (HR = 0.68, 95% CI 0.52-0.88) and OS (HR = 0.54, 95% CI 0.44-0.66) than the patients who did not receive chemotherapy. CONCLUSION: According to current clinical guidelines, patients with stage T1bN0M0 TNBC are probably overtreated. The prognosis of these patients with stage T1aN0M0 or T1bN0M0 disease is good enough that adjuvant chemotherapy cannot improve it further.
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Quimioterapia Adjuvante/métodos , Bases de Dados Factuais/estatística & dados numéricos , Programa de SEER , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
AIMS: The aim of this study was to evaluate the ideal timing of PORT in the management of completely resected (R0) Stage IIIA-N2 NSCLC. PATIENTS AND METHODS: Between January 2008 and December 2015, patients with known histologies of pathologic Stage IIIA-N2 NSCLC who underwent R0 resection and received PORT concurrent with or prior to two sequential cycles of chemotherapy ("early PORT") or with PORT administered after two cycles of chemotherapy ("late PORT") at multiple hospitals. The primary endpoint was OS; secondary end points included pattern of the first failure, LRRFS, and DMFS. Kaplan-Meier OS, LRRFS, and DMFS curves were compared with the log-rank test. Cox regression analysis was used to determine prognosticators for OS, LRRFS, and DMFS. RESULTS: Of 112 included patients, 41 (36.6%) and 71 (63.4%) patients received early PORT and late PORT, respectively. The median OS, LRRFS, and DMFS were longer for those who received early PORT than for those who received late PORT at the median follow-up of 29.6 months (all p < 0.05). Uni- and multi-variate analyses showed that number of POCT cycles and the combination schedule of PORT and POCT were independent prognostic factors for OS, LRRFS, and DMFS. CONCLUSIONS: Early PORT is associated with improved outcomes in pathologic Stage IIIA-N2 R0 NSCLC patients.
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BACKGROUND AND AIM: A matched-pair comparison was performed to compare the efficacy and safety of sublobar resection versus radiotherapy for high-risk elderly patients with Stage I non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We searched the Cochrane Library, MEDLINE, CENTRAL, EMBASE and manual searches. The meta-analysis was performed to compare overall survival, pattern of failure, and toxicity among the homogeneous studies. Subdivided analyses were also performed. RESULTS: Sixteen studies containing 11540 patients were included in the meta-analysis. Among these studies, 9 were propensity-score matched (PSM) cohort studies, and 7 were cohort studies. Sublobar resection, compared with radiotherapy (either conventional fraction radiation therapy or stereotactic body radiation therapy), significantly improved the overall survival regardless in both PSM and non-PSM analyses (all p < 0.05). However, the difference in the pattern of failure and toxicity were not significant (all p > 0.05). CONCLUSIONS: Sublobar resection was associated with improved outcomes in high-risk elderly patients with Stage I NSCLC, which supports the need to compare both treatments in large prospective, randomized, controlled clinical trials.
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Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Pneumonectomia/mortalidade , Radioterapia/mortalidade , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Ensaios Clínicos como Assunto , Humanos , Análise por Pareamento , Estadiamento de Neoplasias , Pontuação de Propensão , Estudos Prospectivos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: This retrospective study evaluated the role of adjuvant radiotherapy (AR) after surgery in patients with uterine sarcoma and analyzed the prognostic factors of local-regional failure-free survival (LRFFS) and overall survival (OS). PATIENTS AND METHODS: A study of a total of 182 patients with uterine sarcoma was conducted between June 1994 and October 2014. Adjuvant radiotherapy was defined as postoperative external beam radiation to the pelvis (30-50 Gray/10-25 fractions at five fractions/week). The primary end point was LRFFS, and the secondary end point was OS. Kaplan-Meier curves were compared using the log-rank test. Cox regression analyses were used to determine prognosticators for LRFFS and OS. RESULTS: The median follow-up time of all patients was 75 months, with a 5-year LRFFS of 62.1%. The 2-year and 5-year LRFFS rates were longer for those who received AR than for those who did not receive AR (83.4% vs 70.3%; 78% vs 55.3%; P=0.013). The 5-year OS of all patients was 56.2%, and no significant differences were observed in the 2-year and 5-year OS rates between these two groups (82.7% vs 71.4%; 64.1% vs 51.7%; P=0.067). Importantly, in patients with leiomyosarcoma, the 2-year and 5-year LRFFS and OS rates were longer for those who received AR than for those who did not receive AR (P=0.04 and P=0.02 for the 2-year and 5-year LRFFS, respectively). CONCLUSION: Patients with uterine sarcoma who were treated with AR after surgery demonstrated an improved LRFFS compared with those who were treated with surgery alone, especially those patients with leiomyosarcoma. Therefore, the role of personalized adjuvant radiation for patients with uterine sarcoma still requires further discussion.
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BACKGROUND: Incidence rates of breast cancer continue to rise in the People's Republic of China. The purpose of this study was to describe Chinese trends in radical surgical modalities and influential imaging and demographic factors for breast malignancies. MATERIALS AND METHODS: This study was a hospital-based, multicenter, 10-year (1999-2008), retrospective study. Descriptive statistical tests were used to illustrate information regarding radical surgical trends for the treatment of breast malignancies. Chi-square tests were used to assess effect of demographic factors in addition to imaging and pathological data on the specific surgical method. RESULTS: A total of 4,211 patients were enrolled in the survey. Among them, 3,335 patients with stage 0 to stage III disease undergoing mastectomy or breast-conserving surgery (BCS) were included in the final analysis. The rate of BCS increased from 1.53% in 1999 to 11.88% in 2008. The rate of mastectomy declined over this time period, from 98.47% in 1999 to 88.12% in 2008, with increasing use of diagnostic imaging methods and pathological biopsies. A significantly greater percentage of patients with office work, high education levels, unmarried status, younger age, and early pathological stages preferred BCS compared with mastectomy. CONCLUSION: Rates of mastectomy in China remain elevated due to diagnosis at higher stages; however, because of increased use of diagnostic imaging, improvement of biopsy methods, and patient education, rates of less invasive lumpectomy are increasing and rates of mastectomy have decreased in China. IMPLICATIONS FOR PRACTICE: In this study, 4,211 cases were collected from 1999 to 2008 through a multicenter retrospective study of varying geographic and socioeconomic areas to illustrate trends of surgeries in the People's Republic of China. The correlations between demographic and tumor characteristics and among methods of surgical treatment were explored. This study shows that the rate of breast-conserving surgery (BCS) increased and the rate of mastectomy declined over this time period with increasing use of diagnostic imaging methods and pathological biopsies. Patients with office work, high education levels, unmarried status, younger age, and early pathological stages preferred BCS compared with mastectomy in China.
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Neoplasias da Mama/cirurgia , Mastectomia/métodos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , China , Feminino , Humanos , Mastectomia/tendências , Mastectomia Segmentar/métodos , Mastectomia Segmentar/tendências , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVE: Incidence of and mortality rates for breast cancer continue to rise in the People's Republic of China. The purpose of this study was to analyze differences in characteristics of breast malignancies between China and the U.S. METHODS: Data from 384,262 breast cancer patients registered in the U.S. Surveillance, Epidemiology, and End Results (SEER) program from 2000 to 2010 were compared with 4,211 Chinese breast cancer patients registered in a Chinese database from 1999 to 2008. Outcomes included age, race, histology, tumor and node staging, laterality, surgical treatment method, and reconstruction. The Pearson chi-square and Fisher's exact tests were used to compare rates. RESULTS: Infiltrating ductal carcinoma was the most common type of malignancy in the U.S. and China. The mean number of positive lymph nodes was higher in China (2.59 vs. 1.31, p < .001). Stage at diagnosis was higher in China (stage IIA vs. I, p < .001). Mean size of tumor at diagnosis was higher in China (32.63 vs. 21.57 mm). Mean age at diagnosis was lower in China (48.28 vs. 61.29 years, p < .001). Moreover, 2.0% of U.S. women underwent radical mastectomy compared with 12.5% in China, and 0.02% in China underwent reconstructive surgery. CONCLUSION: Chinese women were diagnosed at younger ages with higher stage and larger tumors and underwent more aggressive surgical treatment. Prospective trials should be conducted to address screening, surgical, and tumor discrepancies between China and the U.S. IMPLICATIONS FOR PRACTICE: Breast cancer patients in China are diagnosed at later stages than those in America, which might contribute to different clinical management and lower 5-year survival rate. This phenomenon suggests that an earlier detection and treatment program should be widely implemented in China. By comparing the characteristics of Chinese and Chinese-American patients, we found significant differences in tumor size, lymph nodes metastasis, and age at diagnosis. These consequences indicated that patients with similar genetic backgrounds may have different prognoses due to the influence of environment and social economic determinates.
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Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , China/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Programa de SEER , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: For decades, studies have been performed to evaluate the association between ABO blood groups and risk of cancer. However, whether ABO blood groups are associated with overall cancer risk remains unclear. We therefore conducted a meta-analysis of observational studies to assess this association. MATERIALS AND METHODS: A search of Pubmed, Embase, ScienceDirect, Wiley, and Web of Knowledge databases (to May 2013) was supplemented by manual searches of bibliographies of key retrieved articles and relevant reviews. We included case-control studies and cohort studies with more than 100 cancer cases. RESULTS: The search yielded 89 eligible studies that reported 100,554 cases at 30 cancer sites. For overall cancer risk, the pooled OR was 1.12 (95%CI: 1.09-1.16) for A vs. non- A groups, and 0.84 (95%CI: 0.80-0.88) for O vs. non-O groups. For individual cancer sites, blood group A was found to confer increased risk of gastric cancer (OR=1.18; 95%CI: 1.13-1.24), pancreatic cancer (OR=1.23; 95%CI: 1.15-1.32), breast cancer (OR=1.12; 95%CI: 1.01-1.24), ovarian cancer (OR=1.16; 95%CI: 1.04-1.27), and nasopharyngeal cancer (OR=1.17; 95%CI: 1.00-1.33). Blood group O was found to be linked to decreased risk of gastric cancer (OR=0.84; 95%CI: 0.80-0.88), pancreatic cancer (OR=0.75; 95%CI: 0.70-0.80), breast cancer (OR=0.90; 95%CI: 0.85-0.95), colorectal cancer (OR=0.89; 95%CI: 0.81-0.96), ovarian cancer (OR=0.76; 95%CI: 0.53-1.00), esophagus cancer (OR=0.94; 95%CI: 0.89-1.00), and nasopharyngeal cancer (OR=0.81; 95%CI: 0.70-0.91). CONCLUSIONS: Blood group A is associated with increased risk of cancer, and blood group O is associated with decreased risk of cancer.
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Sistema ABO de Grupos Sanguíneos/fisiologia , Suscetibilidade a Doenças/etiologia , Suscetibilidade a Doenças/fisiopatologia , Neoplasias/etiologia , Neoplasias/fisiopatologia , Estudos de Casos e Controles , Estudos de Coortes , Humanos , RiscoRESUMO
Anthracycline-Taxane chemotherapy is widely used in neoadjuvant treatment for breast cancers. However, there is limited data reported in patients with triple negative breast cancer (TNBC). Here, we evaluated the pathologic responses and survival of neoadjuvant epirubicin and taxanes chemotherapy in patients with locally advanced TNBC to provide some useful information for clinical practice. A total of 43 patients with locally advanced TNBC were enrolled in this study. Patients were administered with epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2) or docetaxel 75 mg/m(2) every 3 weeks for at least 2 cycles. The primary endpoint was pathologic complete response (pCR), which was defined as no residual invasive cancer, or only carcinoma in situ in both the excised breast and axillary lymph node, while relapse-free survival (RFS) and overall survival (OS) were secondary endpoints. Thirty-nine (90.7%) patients were at clinical stages IIB-IIIC. Thirty-seven (86%) completed 4-6 cycles of preoperative chemotherapy, and objective response rate (ORR) was 81.4% (35/43). Forty-two patients underwent radical surgery subsequently. The pCR rate was 14.3% (6/42). The most common adverse events in neoadjuvant chemotherapy were nausea/vomiting (88.4%, 38/43) and neutropenia (88.4%). After a median follow-up period of 34.0 months, 3-year RFS and OS rate was 53.6% and 80.1%, respectively. All events of recurrence and death occurred in non-pCR patients, in whom the 3-year RFS and OS rates were 44.3% and 76.6%, respectively. This study suggest that neoadjuvant chemotherapy with epirubicin plus taxanes has a relatively low pCR rate and high early recurrence risk in locally advanced TNBC, which indicates the necessity for more efficacious treatment. Further study is needed to validate these results.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Idoso , Quimiorradioterapia Adjuvante/métodos , Intervalo Livre de Doença , Docetaxel , Epirubicina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Neoplasia Residual/patologia , Neoplasia Residual/prevenção & controle , Paclitaxel/administração & dosagem , Taxoides/administração & dosagem , Falha de Tratamento , Resultado do TratamentoRESUMO
The clinical success of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) as therapeutic agents has prompted great interest in their further development and clinical testing for a wide variety of malignancies. However, most studies have focused on the efficacy of TKI, and few studies have been done on the criteria for their discontinuation. The current standard for drug discontinuation is "until progression", based on change in tumor size. However, tumor size is not related to the gene expression which determines the efficacy of TKI in the final analysis, and it is also difficult to make a thorough and correct prediction based on tumor size when the TKI is discontinued. Nevertheless, clinical evaluation of the criteria for TKI discontinuation is still in its early days. Some promising findings have started to emerge. With the improving knowledge of EGFR and its inhibitors, it is expected that the criteria for discontinuation of EGFR inhibitor therapy will become clearer.
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OBJECTIVE: To evaluate the efficacy, safety and survival of combination of carboplatin plus paclitaxel as neoadjuvant chemotherapy (NACT) for patients with locally advanced triple-negative breast cancer (TNBC), and explore an optimal regimen for TNBC. METHODS: Patients with core needle biopsy confirmed pathological diagnosis of IIA â¼ IIIC invasive breast cancer, negative for estrogen and progesterone receptors and HER2 by immunohistochemistry, and with indication for NACT were eligible in this study. The biopsy tumor tissues were tested for CK5/6, CK14, EGFR and Ki67. The patients received paclitaxel 175 mg/m(2) on day 1, carboplatin at an area under the curve 5 mg×min/ml on day 2 of every 21 days. The clinical response was evaluated every 2 cycles according to Standard RECIST 1.0 criteria and surgery was done after four to six cycles. Pathological complete remission (pCR) was defined if absence of invasive tumor in the breast and axillary lymph nodes samples or residual carcinoma in situ only. RESULTS: Overall, thirty-one patients were enrolled from January 2008 to November 2010. The median age was 51 years and 83.9% of the patients were diagnosed as stage IIB to IIIC diseases. 30 Patients completed chemotherapy as planed while one patient changed regimen due to paclitaxel allergy. Twenty-eight patients could be evaluated for clinical efficacy, of which CR, PR, SD, PD were achieved in 4, 20, 3 and 1 women, respectively. The objective response rate was 85.7%. The expression rate of CK5/6, CK14 and EGFR were 88.9% (24/27), 59.3% (16/27) and 63% (17/27), respectively. Among 27 patients who received modified radical mastectomy or breast-conserving surgery, 11 patients obtained pCR, with a pCR rate of 40.7% (95%CI 22.2% - 59.3%). Five of six CK5/6- and CK14-positive patients achieved pCR. All the 31 patients could be evaluated for toxicity according to the NCI-CTC v3.0 criteria. The major toxicities were neutropenia (93.5%), vomiting (45.2%) and ALT/AST increase (32.3%), and grade 3-4 toxicities accounted for 74.2%, 3.2%, 0, respectively. Until December 2011, at a median follow-up of 28.9 months (range 5 - 47.9), eight patients developed recurrence including 5 patients died. Among 11 patients with pCR, one suffered from lung metastasis at 45 months after diagnosis and survived with tumor until now. The other ten were alive and disease free. The 3-year DFS and OS were 62% and 74.7%, respectively. CONCLUSIONS: As a neoadjuvant treatment for triple-negative breast cancer, carboplatin plus paclitaxel regimen achieves notable higher objective response rate and pCR rate compared with the anthracycline plus paclitaxel regimen reported in the literature, and is well tolerable. It is an optimized regimen for TNBC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carboplatina/administração & dosagem , Carcinoma Ductal de Mama/tratamento farmacológico , Paclitaxel/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biópsia com Agulha de Grande Calibre , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Indução de Remissão , Taxa de Sobrevida , Adulto JovemRESUMO
OBJECTIVE: We have identified a SNP within the seed-binding region for miR-502 in the 3'-UTR of the SET8 gene that codes for a methyltransferase for histone H4. SET8 methylates TP53 and thus regulates cell proliferation and genome stability. This study is to investigate the role for this SNP and its interaction with the TP53 codon 72 SNP in the age of onset of breast cancer. METHODS: We conducted a case-only study of 1, 110 breast cancer cases. PCR-RFLP was used for SNP genotyping. Ages of onset of breast cancer among different genotypes were analyzed using SAS software. RESULTS: Our analysis revealed that the SET8 CC and TP53 GG genotypes were independently associated with earlier age of onset of breast cancer in an allele-dose dependent manner. Moreover, individuals with both SET8 CC and p53 GG genotypes developed cancer at age of 47.74 years, compared with 54.55 years for individuals with both SET8 TT and TP53 CC genotypes. CONCLUSIONS: miR-502-binding SNP in SET8 may modulate SET8 expression and contribute to early development of breast cancer either independently or together with the TP53 codon 72 SNP.
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Neoplasias da Mama/genética , Histona-Lisina N-Metiltransferase/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Proteína Supressora de Tumor p53/genética , Regiões 3' não Traduzidas/genética , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Sítios de Ligação/genética , Códon , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Adulto JovemRESUMO
BACKGROUND: Although chemotherapy is one of the most important treatments of breast cancer, it is limited by significant inter-individual variations in response and toxicity. The metabolism of epirubicin (EPI) and cyclophosphamide (CTX) is mainly mediated by cytochrome P450s (CYPs) and glutathione S-transferases (GSTs). It has been well-known that the activities of these enzymes are polymorphic in population due to their genetic polymorphisms. The aim of this research was to examine the effects of genetic polymorphisms in CYP3A, GSTP1 and MDR1 genes on treatment response and side-effects of breast cancer patients receiving EPI/CTX chemotherapy. METHODS: One hundred and twenty patients with stage II or III invasive breast cancer were recruited and treated with three to four cycles of EPI 80 mg/m(2) and CTX 600 mg/m(2) every two weeks. The AJCC TNM staging system (sixth edition) was used to evaluate the pathological response of primary tumor and axillary lymph nodes. The genotypes of gene polymorphisms were determined by using PCR-restriction fragment length polymorphism methods. RESULTS: Patients carrying GSTP1 (105)Ile/Val or (105)Ile/Ile genotype were more likely to have good response (OR, 0.40; 95%CI, 0.16 - 0.96; P = 0.024) and light toxicity (OR, 0.35; 95%CI, 0.13 - 0.78; P = 0.006) than those carrying (105)Val/Val genotypes. The response to the treatment was not correlated with estrogen receptor, progesterone receptor and Her2/neu status of tumors. No correlation was found between toxicity effect and patient's age, tumor staging, menopause status, and dose intensity of the drugs. CONCLUSION: GSTP1 polymorphism was associated with the chemotherapy response or adverse effects of EPI and CTX regimens.
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Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Glutationa S-Transferase pi/genética , Adulto , Idoso , Neoplasias da Mama/genética , Ciclofosfamida/uso terapêutico , Epirubicina/uso terapêutico , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
OBJECTIVE: To analyze the trend of the incidence of prostate cancer in urban Tianjin area between 1981 and 2004 so as to provide scientific rationales for the prevention and control of prostate cancer. METHODS: The data of prostate cancer cases were provided by the Tianjin Cancer Registry. The SAS system V9 was used to calculate the crude incidence, age-adjusted incidence and age specific incidence of prostate cancer in Tianjin between 1981 and 2004. And the Join point 3.0 software was used to analyze secular trends. RESULTS: Between 1981 and 2004, a total of 1060 prostate cancer cases were diagnosed in Tianjin. And the age-adjusted incidence rate was 2.84/100 000 in 2004. The incidence of prostate cancer showed 3 incremental stages during the 24-year period at an annual average of 4.02%. An aging trend was observed for prostate cancer patients. The elder patients had a faster increment in incidence. Specifically, it increased annually at 4.63% for age group 65 - 74 year versus 5.18% for age group 75 years or more. CONCLUSION: Despite a low incidence of prostate cancer in Tianjin, it is increasing at a fast rate. The prevention and control of prostate cancer should be strengthened.
Assuntos
Neoplasias da Próstata/epidemiologia , Sistema de Registros , Adulto , Idoso , China/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To evaluate the sensitivity, specificity of touch imprint cytology (TIC), and to compare its conformity rate with histopathology, to observe the consistence of immunocytochemistry (ICC) with immunohistochemistry (IHC), and to assess the diagnostic value of TIC prior to neoadjuvant chemotherapy for breast cancer. METHODS: 289 cases of TIC and 287 cases with core needle biopsy (CNB) histopathology accumulated from October 2005 to October 2008 in our hospital were included in this study. One hundred ninety cases TIC results were compared with that of final histopathology. 64 cases were tested for ER, PR, HER-2 by immunocytochemistry. RESULTS: Twenty-four benign cases and 263 malignant cases were diagnosed. 4 specimens were unsatisfactory. False negative rate and unsatisfactory rate were 1.4%, both, and false positive rate was 0.35%. The accuracy rate of TIC and CNB was 95.8% and 95.3%, respectively (P = 0.804). The sensitivity of TIC and CNB was 96.2% and 95.0% (P = 0.601), specificity 87.5% and 100% (P = 0.471) were found, when compared with the results of routine histopathology. 52 cases had a control with IHC of CNB in 64 ICC, and 43 cases had a final histopathology IHC. The ICC conformity rate of ER, PR, HER-2 with IHC of CNB was 86.5%, 75.0%, 78.8%, and that with IHC of final histopathology was 88.4%, 74.4%, 75.6%, respectively. The conformity rate of IHC between CNB and final histopathology was 83.7%, 74.4%, 76.5%, respectively. There was no significant statistical difference between them. CONCLUSION: Compared with routine CNB histopathology, TIC has a high accuracy and sensitivity, and can provide a rapid and reliable cytological diagnosis to complement CNB for breast lesions. The conformity rates are high in ER, PR, HER-2 expression between ICC and IHC. ICC of TIC can be used to determine the estrogen and progesterone receptor levels in breast cancer before neoadjuvant chemotherapy.
Assuntos
Biópsia por Agulha/métodos , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Citodiagnóstico/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Erros de Diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Sensibilidade e Especificidade , Adulto JovemRESUMO
The aim of this study was to observe the effect of interferon alpha (IFNalpha) on tumor endothelial cells (TECs) in highly metastatic hepatocellular carcinoma (HCC) model, and to investigate the underlying mechanism. Nude mice with HCC xenograft were treated with IFNalpha. Gene expression profiles of TECs were analyzed by utilizing cDNA microarray. The differentiation of tumor blood vessels was evaluated by CD31/alphaSMA dual immunohistochemistry. Apoptosis of TECs was determined by CD31/TUNEL double staining. The functions of TECs in adhesion and uptake of acetylated low-density lipoprotein were observed in vitro. Results showed that IFNalpha effectively inhibited HCC tumor growth, with decreased microvessel density, increased apoptosis in TECs and normalized tumor blood vessels. cDNA microarray analysis revealed differential gene expression patterns in TECs under the treatment of IFNalpha. The cell-cell contact distribution of VE-Cadherin and uptake of acetylated low-density lipoprotein were significantly inhibited by IFNalpha in cultivated TECs. These results suggest that IFNalpha may induce apoptosis and interfere with hemophilic adhesion of TECs. The changes of gene expression in TECs contribute essentially to its effect of anti-angiogenesis and the subsequent inhibition of tumor progression.
Assuntos
Inibidores da Angiogênese/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Interferon-alfa/farmacologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Animais , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/patologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Células Endoteliais/efeitos dos fármacos , Imunofluorescência , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Neoplasias Hepáticas Experimentais/irrigação sanguínea , Neoplasias Hepáticas Experimentais/patologia , Masculino , Camundongos , Camundongos Nus , Análise de Sequência com Séries de Oligonucleotídeos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To investigate the histological criteria of breast cancer response to neoadjuvant therapy. METHODS: One hundred and fifty-four cases of breast cancer receiving neoadjuvant therapy were collected from June, 2005 to June, 2007 and the clinical data were analyzed. All patients were operated on within 4 weeks after neoadjuvant therapy. All specimens were assessed by the standard method of Miller and Payne (MP) grading system. The response to neoadjuvant therapy were assessed by two pathologists independently, using MP grading system and common grading system separately. RESULTS: The response rate using the MP grading system were grade 1 in 12 cases (7.8%), grade 2 in 33 cases (21.4%), grade 3 in 64 cases (41.6%), grade 4 in 31 cases (20.1%) and grade 5 in 14 cases (9.1%). Using the common grading system, the response were mild in 51 cases (33.1%), moderate in 71 cases (46.1%) and severe in 32 cases (20.8%). MP grading system may be related to common grading system (chi2 = 186.660, P < 0.01). Follow up information were available in 147 cases, with 14 cases showing recurrence, metastasis or death from the disease. The MP grading system may be related to the outcome (chi2 = 11.612, P = 0.020), but not the common grading system (chi2 = 0.881, P = 0.644). CONCLUSION: MP grading system may be one of the prognostic factors in the neoadjuvant therapy of breast cancer.