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1.
ESMO Open ; 9(5): 103009, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38663168

RESUMO

BACKGROUND: The GENEVIEVE study, comparing neoadjuvant cabazitaxel versus paclitaxel in triple-negative breast cancer (TNBC) and luminal B/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC), previously reported significant differences in pathological complete response (pCR) rates. Effects on long-term outcome are unknown. PATIENTS AND METHODS: GENEVIEVE randomized patients with cT2-3, any cN or cT1, cN+/pNSLN+, centrally confirmed TNBC or luminal B/HER2-negative BC (latter defined as estrogen/progesterone receptor-positive and >14% Ki-67-stained cells) to receive either cabazitaxel 25 mg/m2 q3w for four cycles or paclitaxel 80 mg/m2 weekly for 12 weeks. Anthracycline-containing chemotherapy was allowed in case of histologically proven invasive residuals as neoadjuvant treatment or after surgery as adjuvant treatment. Here we report the secondary endpoints invasive disease-free survival (iDFS), distant disease-free survival (DDFS), and overall survival (OS). RESULTS: Of the 333 patients randomized, 74.7% and 83.2% completed treatment in the cabazitaxel and paclitaxel arms, respectively. After a median follow-up of 89.3 months (interquartile range 68.8-97.3 months), 80 iDFS events (43 after cabazitaxel and 37 after paclitaxel) and 47 deaths (23 after cabazitaxel and 24 after paclitaxel) were reported. IDFS rates were not significantly different between the cabazitaxel and paclitaxel arms after a 3-year (83.6% versus 85.0%) and 5-year follow-up (76.2% versus 78.3%) [hazard ratio (HR) = 1.27, 95% confidence interval 0.82-1.96, P = 0.294], respectively. DDFS rates at 3 years (88.6% versus 87.8%) and 5 years (82.1% versus 82.8%) for cabazitaxel and paclitaxel were comparable (HR = 1.15, P = 0.573). Similarly, OS rates at 3 years (91.6% versus 91.8%) and 5 years (89.2% versus 86.8%) showed no significant differences (HR = 1.05, P = 0.872). Subgroup analysis for TNBC and luminal B/HER2-negative BCs indicated no significant variations in 3- or 5-year iDFS, DDFS, or OS. CONCLUSIONS: The significant differences in pCR rates observed in both treatment arms did not significantly impact long-term outcomes for patients treated with cabazitaxel versus paclitaxel in the GENEVIEVE trial.


Assuntos
Terapia Neoadjuvante , Paclitaxel , Taxoides , Neoplasias de Mama Triplo Negativas , Humanos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Feminino , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Adulto , Taxoides/uso terapêutico , Taxoides/farmacologia , Idoso , Resultado do Tratamento , Receptor ErbB-2/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Intervalo Livre de Doença
2.
Ann Oncol ; 33(11): 1149-1158, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35961599

RESUMO

BACKGROUND: Addition of immune checkpoint inhibitors to neoadjuvant chemotherapy (NACT) is a promising strategy in early breast cancer, but the optimal duration of therapy is currently unknown. In the GeparNuevo (NCT02685059) trial, addition of durvalumab to NACT as previously reported led to a moderate increase in pathological complete response (pCR) rate by an absolute 9% (P = 0.287). PATIENTS AND METHODS: Patients with cT1b-cT4a-d triple-negative breast cancer (TNBC) received durvalumab 1.5 g or placebo every 4 weeks added to nab-paclitaxel 125 mg/m2 weekly for 12 weeks, followed by durvalumab/placebo every 4 weeks plus epirubicin/cyclophosphamide every 2 weeks followed by surgery. Durvalumab was not continued after surgery. The primary objective was pCR. Secondary endpoints included invasive disease-free survival (iDFS), distant disease-free survival (DDFS) and overall survival (OS). RESULTS: A total of 174 patients were randomised between June 2016 and October 2017. After a median follow-up of 43.7 months, 34 events had occurred. Despite a non-significant increase in the pCR rate, significant differences were observed for 3-year iDFS, DDFS and OS: iDFS was 85.6% with durvalumab versus 77.2% with placebo [hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.24-0.97, stratified log-rank P = 0.036]; DDFS 91.7% versus 78.4% (HR 0.31, 95% CI 0.13-0.74, P = 0.005); OS 95.2% versus 83.5% (HR 0.24, 95% CI 0.08-0.72, P = 0.006). pCR patients had 3-year iDFS of 95.5% with durvalumab and 86.1% without (HR 0.22, 95% CI 0.05-1.06). In the non-pCR cohort 3-year iDFS was 76.3% versus 69.7% (HR 0.67, 95% CI 0.29-1.54). Multivariable analysis confirmed a durvalumab effect independent of the pCR effect. No new safety signals occurred. CONCLUSIONS: Durvalumab added to NACT in TNBC significantly improved survival despite a modest pCR increase and no adjuvant component of durvalumab. Additional studies are needed to clarify the optimal duration and sequence of checkpoint inhibitors in the treatment of early TNBC.


Assuntos
Terapia Neoadjuvante , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida , Intervalo Livre de Doença
3.
ESMO Open ; 7(3): 100495, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35653983

RESUMO

BACKGROUND: Up to 40% of patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer develop brain metastases (BMs). Understanding of clinical features of these patients with HER2-positive breast cancer and BMs is vital. PATIENTS AND METHODS: A total of 2948 patients from the Brain Metastases in Breast Cancer registry were available for this analysis, of whom 1311 had primary tumors with the HER2-positive subtype. RESULTS: Patients with HER2-positive breast cancer and BMs were-when compared with HER2-negative patients-slightly younger at the time of breast cancer and BM diagnosis, had a higher pathologic complete response rate after neoadjuvant chemotherapy and a higher tumor grade. Furthermore, extracranial metastases at the time of BM diagnosis were less common in HER2-positive patients, when compared with HER2-negative patients. HER2-positive patients had more often BMs in the posterior fossa, but less commonly leptomeningeal metastases. The median overall survival (OS) in all HER2-positive patients was 13.2 months (95% confidence interval 11.4-14.4). The following factors were associated with shorter OS (multivariate analysis): older age at BM diagnosis [≥60 versus <60 years: hazard ratio (HR) 1.63, P < 0.001], lower Eastern Cooperative Oncology Group status (2-4 versus 0-1: HR 1.59, P < 0.001), higher number of BMs (2-3 versus 1: HR 1.30, P = 0.082; ≥4 versus 1: HR 1.51, P = 0.004; global P = 0.015), BMs in the fossa anterior (HR 1.71, P < 0.001), leptomeningeal metastases (HR 1.63, P = 0.012), symptomatic BMs at diagnosis (HR 1.35, P = 0.033) and extracranial metastases at diagnosis of BMs (HR 1.43, P = 0.020). The application of targeted therapy after the BM diagnosis (HR 0.62, P < 0.001) was associated with longer OS. HER2-positive/hormone receptor-positive patients showed longer OS than HER2-positive/hormone receptor-negative patients (median 14.3 versus 10.9 months; HR 0.86, P = 0.03), but no differences in progression-free survival were seen between both groups. CONCLUSIONS: We identified factors associated with the prognosis of HER2-positive patients with BMs. Further research is needed to understand the factors determining the longer survival of HER2-positive/hormone receptor-positive patients.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Neoplasias Encefálicas/secundário , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Receptor ErbB-2/metabolismo , Receptor ErbB-2/uso terapêutico , Sistema de Registros
4.
Ann Oncol ; 32(12): 1590-1596, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34520831

RESUMO

BACKGROUND: Current genetic and genomic tests measuring homologous recombination deficiency (HRD) show limited predictive value. This study compares the performance of an immunohistology-based RAD51 test with genetic/genomic tests to identify patients with HRD primary triple-negative breast cancer (TNBC) and evaluates its accuracy to select patients sensitive to platinum-based neoadjuvant chemotherapy (NACT). PATIENTS AND METHODS: This is a retrospective, blinded, biomarker analysis from the GeparSixto randomized clinical trial. TNBC patients received neoadjuvant paclitaxel plus Myocet®-nonpegylated liposomal doxorubicin (PM) or PM plus carboplatin (PMCb), both arms including bevacizumab. Formalin-fixed paraffin-embedded (FFPE) tumor samples were laid on tissue microarrays. RAD51, BRCA1 and γH2AX were quantified using an immunofluorescence assay. The predictive value of RAD51 was assessed by regression models. Concordance analyses were carried out between RAD51 score and tumor BRCA (tBRCA) status or genomic HRD score (Myriad myChoice®). Associations with pathological complete response (pCR) and survival were studied. Functional HRD was predefined as a RAD51 score ≤10% (RAD51-low). RESULTS: Functional HRD by RAD51-low was evidenced in 81/133 tumors (61%). RAD51 identified 93% tBRCA-mutated tumors and 45% non-tBRCA mutant cases as functional HRD. The concordance between RAD51 and genomic HRD was 87% [95% confidence interval (CI) 79% to 93%]. In patients with RAD51-high tumors, pCR was similar between treatment arms [PMCb 31% versus PM 39%, odds ratio (OR) 0.71, 0.23-2.24, P = 0.56]. Patients with RAD51-low tumors benefited from PMCb (pCR 66% versus 33%, OR 3.96, 1.56-10.05, P = 0.004; interaction test P = 0.02). This benefit maintained statistical significance in the multivariate analysis. Carboplatin addition showed similar disease-free survival in the RAD51-high [hazard ratio (HR) 0.40, log-rank P = 0.11] and RAD51-low (0.45, P = 0.11) groups. CONCLUSIONS: The RAD51 test identifies tumors with functional HRD and is highly concordant with tBRCA mutation and genomic HRD. RAD51 independently predicts clinical benefit from adding Cb to NACT in TNBC. Our results support further development to incorporate RAD51 testing in clinical decision-making.


Assuntos
Neoplasias de Mama Triplo Negativas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteína BRCA1/genética , Carboplatina/uso terapêutico , Recombinação Homóloga , Humanos , Rad51 Recombinase/genética , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética
5.
Ann Oncol ; 29(12): 2341-2347, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30335131

RESUMO

Background: In the neoadjuvant GeparSixto study, adding carboplatin to taxane- and anthracycline-based chemotherapy improved pathological complete response (pCR) rates in patients with triple-negative breast cancer (TNBC). Here, we present survival data and the potential prognostic and predictive role of homologous recombination deficiency (HRD). Patients and methods: Patients were randomized to paclitaxel plus nonpegylated liposomal doxorubicin (Myocet®) (PM) or PM plus carboplatin (PMCb). The secondary study end points disease-free survival (DFS) and overall survival (OS) were analyzed. Median follow-up was 47.3 months. HRD was among the exploratory analyses in GeparSixto and was successfully measured in formalin-fixed, paraffin-embedded tumor samples of 193/315 (61.3%) participants with TNBC. Homologous recombination (HR) deficiency was defined as HRD score ≥42 and/or presence of tumor BRCA mutations (tmBRCA). Results: A significantly better DFS (hazard ratio 0.56, 95% CI 0.34-0.93; P = 0.022) was observed in patients with TNBC when treated with PMCb. The improvement of OS with PMCb was not statistically significant. Additional carboplatin did not improve DFS or OS in patients with HER2-positive tumors. HR deficiency was detected in 136 (70.5%) of 193 triple-negative tumors, of which 82 (60.3%) showed high HRD score without tmBRCA. HR deficiency independently predicted pCR (ypT0 ypN0) [odds ratio (OR) 2.60, 95% CI 1.26-5.37, P = 0.008]. Adding carboplatin to PM significantly increased the pCR rate from 33.9% to 63.5% in HR deficient tumors (P = 0.001), but only marginally in HR nondeficient tumors (from 20.0% to 29.6%, P = 0.540; test for interaction P = 0.327). pCR rates with carboplatin were also higher (63.2%) than without carboplatin (31.7%; OR 3.69, 1.46-9.37, P = 0.005) in patients with high HRD score but no tmBRCA. DFS rates were improved with addition of carboplatin, both in HR nondeficient (hazard ratio 0.44, 0.17-1.17, P = 0.086) and HR deficient tumors (hazard ratio 0.49, 0.23-1.04, P = 0.059). Conclusions: The addition of carboplatin to neoadjuvant PM improved DFS significantly in TNBC. Long-term survival analyses support the neoadjuvant use of carboplatin in TNBC. HR deficiency in TNBC and HRD score in non-tmBRCA TNBC are predictors of response. HRD does not predict for carboplatin benefit.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Reparo de DNA por Recombinação/genética , Neoplasias de Mama Triplo Negativas/terapia , Antraciclinas/farmacologia , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Proteína BRCA1/genética , Proteína BRCA2/genética , Mama/patologia , Mama/cirurgia , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Carboplatina/farmacologia , Intervalo Livre de Doença , Doxorrubicina/análogos & derivados , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Seguimentos , Humanos , Mastectomia , Pessoa de Meia-Idade , Mutação , Terapia Neoadjuvante/métodos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Polietilenoglicóis/farmacologia , Polietilenoglicóis/uso terapêutico , Prognóstico , Análise de Sobrevida , Taxoides/farmacologia , Taxoides/uso terapêutico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia
6.
Eur J Cancer ; 64: 12-21, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27323347

RESUMO

BACKGROUND: Patients with invasive residual disease after neoadjuvant chemotherapy (NACT) are considered to have chemo-resistant breast cancer. Bisphosphonates are an established treatment for bone metastases and are of potential benefit as adjuvant treatment in early breast cancer. PATIENTS AND METHODS: Patients who had invasive tumour residuals (ypT1-4 and/or ypN+) after a minimum of four cycles of anthracycline-taxane-containing NACT were eligible for the NeoAdjuvant Trial Add-oN study. Patients were randomised within 3 years after surgery to receive zoledronate 4 mg i.v. for 5 years versus observation. Zoledronate was given every 4 weeks for the first 6 months, every 3 months for the following 2 years, and every 6 months for the last 2.5 years. Primary objective was disease-free survival. RESULTS: After a median time of 54.7 months no difference in disease-free survival was observed between the zoledronate and observation groups (hazard ratio [HR] 0.960, 95% confidence interval [CI] 0.709-1.30, log rank P=0.789). Various subgroups were examined without identifying a treatment effect of zoledronate. Patients over 55 years of age showed a HR of 0.832 in favour of zoledronate, but the result was not significant (P=0.480). A similar result was obtained for overall survival with a HR of 1.19 (95% CI 0.79-1.79; log rank P=0.408). Zoledronate was well tolerated and no new toxicity signal was identified. CONCLUSION: Postneoadjuvant treatment with zoledronate does not improve outcome in patients without pathological complete response after neoadjuvant anthracycline-taxane-based chemotherapy for early breast cancer.


Assuntos
Antineoplásicos/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/prevenção & controle , Neoplasias Ósseas/secundário , Neoplasias da Mama/tratamento farmacológico , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Adulto , Idoso , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasia Residual , Ácido Zoledrônico
7.
Br J Cancer ; 107(11): 1892-900, 2012 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-23079573

RESUMO

BACKGROUND: Biomarkers predictive of pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) of breast cancer are urgently needed. METHODS: Using a training/validation approach for detection of predictive biomarkers in HER2-negative breast cancer, pre-therapeutic core biopsies from four independent cohorts were investigated: Gene array data were analysed in fresh frozen samples of two cohorts (n=86 and n=55). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed in formalin-fixed, paraffin-embedded (FFPE) samples from two neoadjuvant phase III trials (GeparTrio, n=212, and GeparQuattro, n=383). RESULTS: A strong predictive capacity of thymosin beta 15 (TMSB15A) gene expression was evident in both fresh frozen cohorts (P<0.0001; P<0.0042). In the GeparTrio FFPE training cohort, a significant linear correlation between TMSB15A expression and pCR was apparent in triple-negative breast cancer (TNBC) (n=61, P=0.040). A cutoff point was then defined that divided TNBC into a low and a high expression group (pCR rate 16.0% vs 47.2%). Both linear correlation of TMSB15A mRNA levels (P=0.017) and the pre-defined cutoff point were validated in 134 TNBC from GeparQuattro (pCR rate 36.8% vs 17.0%, P=0.020). No significant predictive capacity was observed in luminal carcinomas from GeparTrio and GeparQuattro. CONCLUSION: In TNBC, TMSB15A gene expression analysis might help to select patients with a high chance for pCR after NACT.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Timosina/genética , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Ensaios Clínicos Fase III como Assunto , Receptor alfa de Estrogênio/análise , Feminino , Perfilação da Expressão Gênica , Humanos , Modelos Logísticos , RNA Mensageiro/análise , Receptor ErbB-2/análise , Receptores de Progesterona/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa
8.
Anaesthesist ; 52(5): 419-26, 2003 May.
Artigo em Alemão | MEDLINE | ID: mdl-12750826

RESUMO

A 35-years old gravida IV and para II underwent caesarean section because of fetal distress following induction of labour. During operation the patient developed disseminated intravascular coagulation (DIC), severe haemorrhage and shock necessitating massive blood transfusion,hysterectomy with pelvic packing, and high-dose catecholamines. Ultimately, recombinant factor VIIa was given to control bleeding. During the first 24 hours after operation, both clinical and laboratory findings showed that the severe DIC was on the course to recovery.However, the patient subsequently developed multiple organ dysfunction syndrome with respiratory and renal failure requiring mechanical ventilation and haemodialysis.All therapeutical efforts could not help that the patient passed away due to an inevitable multiple organ failure on the 12th day after the operation. Given the constellation of diagnostic and clinical findings, the most likely diagnosis was amniotic fluid embolism (AFE), a rare complication of pregnancy. The following differential diagnoses were less likely or excluded in this reported patient: pre-eclampsia/pregnancy-induced hypertension,HELLP syndrome,anaphylaxis,uterine rupture, transfusion reactions,pulmonary embolism. AFE occurs rarely, and because studies in animal models cannot reproduce accurately the pathophysiological and clinical alterations seen in humans, its pathogenesis remains unclear. It has been proposed that the clinical syndrome of AFE occurs when fetal antigens pass the maternal immunological barrier in susceptible mothers. The recognition of fetal antigens by maternal immune system subsequently triggers the release of endogenous mediators that are responsible for dramatic pathophysiological disturbances.Furthermore, the components of amniotic fluid initiate the DIC. These events are more consistent with septic shock and anaphylactic shock than with an embolic process and it was proposed that the term "amniotic fluid embolism" be changed to "anaphylactoid syndrome of pregnancy". At present, no therapy has been found to consistently improve outcomes in women with AFE.Patients who survive the initial insult are at high risk for multiple organ failure. The mortality of AFE remains high.


Assuntos
Anafilaxia/fisiopatologia , Embolia Amniótica/fisiopatologia , Complicações na Gravidez/fisiopatologia , Adulto , Anafilaxia/tratamento farmacológico , Anafilaxia/terapia , Transfusão de Sangue , Catecolaminas/uso terapêutico , Cesárea , Coagulação Intravascular Disseminada/fisiopatologia , Embolia Amniótica/tratamento farmacológico , Embolia Amniótica/terapia , Evolução Fatal , Feminino , Humanos , Insuficiência de Múltiplos Órgãos/complicações , Insuficiência de Múltiplos Órgãos/fisiopatologia , Hemorragia Pós-Parto , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/terapia
9.
Am J Obstet Gynecol ; 179(5): 1298-304, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9822520

RESUMO

OBJECTIVE: We investigated to determine whether colposcopic, histologic, and virologic parameters of cervical intraepithelial neoplasia are influenced by a patient's age. STUDY DESIGN: A cohort of 967 women with a mean age of 37.1 years underwent screening for detection of cervical intraepithelial neoplasia by colposcopy, cytologic examination, and testing for high-risk human papillomaviruses with the Hybrid Capture System (Digene, Silver Springs, Md) and a general primer and type-specific primer polymerase chain reaction system. Cervicography was used for documentation and reproducible evaluation of the colposcopic appearance of the cervix. In 86% of patients with trivial colposcopic changes of doubtful significance (100/116) and 89% of patients with colposcopic changes consistent with cervical intraepithelial neoplasia (89/99), punch biopsy specimens were taken for histologic evaluation. RESULTS: In patients with trivial colposcopic changes of doubtful significance, histologically confirmed cervical intraepithelial neoplasia was almost as frequent (32%, 37/116) as in patients with colposcopic changes consistent with cervical intraepithelial neoplasia (43%, 43/99, difference not significant). The ratio between colposcopic evidence of cervical intraepithelial neoplasia and trivial colposcopic changes was 1.9 in patients <35 years old with cervical intraepithelial neoplasia, versus 0.5 in patients >/=35 years old with cervical intra-epithelial neoplasia (P =.005). Patients with trivial colposcopic changes of doubtful significance were older (median age 36 years) than were patients with colposcopic changes consistent with cervical intraepithelial neoplasia (median age 29 years, P =. 008). In patients with cervical intraepithelial neoplasia who had no or trivial colposcopic changes, the thickness of neoplastic epithelium was smaller (P =.008) and the number of cellular layers was lower (P =.01) than in patients with cervical intraepithelial neoplasia who had colposcopic changes consistent with cervical intraepithelial neoplasia. In patients <35 years old the rate of positive results for a high-risk human papillomavirus (P <.005) and the viral load (difference not significant) were higher than in women >/=35 years old. The rate of positive results for high-risk human papillomaviruses differed independently of age among patients with normal colposcopic findings, patients with trivial colposcopic changes of doubtful significance, and patients with colposcopic changes consistent with cervical intraepithelial neoplasia (P <.005). CONCLUSIONS: In women >/=35 years old cervical lesions associated with intraepithelial neoplasia are thinner and thus less colposcopically conspicuous than those in women <35 years old. Patients >/=35 years old with acetowhite cervical lesions consistent with trivial changes of doubtful significance should therefore undergo punch biopsy for histologic evaluation.


Assuntos
Envelhecimento/fisiologia , Colposcopia , Displasia do Colo do Útero/patologia , Adolescente , Adulto , Idoso , Colo do Útero/patologia , Colo do Útero/virologia , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação
10.
Int J Gynecol Pathol ; 16(3): 197-204, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9421083

RESUMO

Distribution of various types of genital human Papillomavirus (HPV) in smears from histologically classified cervical lesions was determined by hybrid capture assay (HCA) and was compared with a polymerase chain reaction (PCR) system using general primers (GP) in first and type specific primers (TS) in a second step. The overall agreement of high-risk HPV by HCA and the more sensitive GP/TS PCR was 80.6% (204 of 253, kappa value 0.6). Human Papillomavirus frequency by GP/TS PCR was 14-20% higher compared with HCA (p = 0.02-0.004) independent of morphology. Only one sample was positive by HCA and negative by GP/TS PCR. A significantly higher frequency was found using HCA and GP/TS PCR in smears from histologically proven cervical intraepithelial lesions (CIN) II/III compared with CIN I, tissues with minimal changes (metaplasia, cervicitis, or lack of glycogenization), or normal morphology (61% and 81% vs 8-15% and 24-34%, p < or = 0.001). Semi-quantitative estimate of HPV DNA copies by GP-PCR coincided with estimated virus load by quantitative HCA and was significantly higher in patients with CIN II/III compared with CIN I (p < 0.001). Thus, the GP-PCR may be used to monitor the amount of HPV DNA copies in clinical samples. A direct correlation between morphologic changes and HPV detection as well as virus load was found by HCA and the more sensitive GP/TS PCR.


Assuntos
Colo do Útero/patologia , Colo do Útero/virologia , DNA Viral/análise , Papillomaviridae/isolamento & purificação , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Adolescente , Adulto , Idoso , Biópsia , Sondas de DNA de HPV , Feminino , Humanos , Metaplasia/complicações , Metaplasia/patologia , Metaplasia/virologia , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade , Infecções Tumorais por Vírus/complicações , Displasia do Colo do Útero/complicações , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia
11.
Gynecol Oncol ; 65(3): 399-404, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9190964

RESUMO

Human papillomavirus (HPV) status in cervical smears from cervical intraepithelial neoplasia (CIN) 2/3 diagnosed in 36 of 892 women with a history of normal cytology and colposcopy (incident CIN 2/3) was compared with CIN 2/3 in 40 patients with a history of abnormal cytology (prevalent CIN 2/3). In all patients cervical smears for HPV testing and cytology and two cervigrams were taken. The scrapes were collected in hybrid capture assay solution and analyzed with the hybrid capture and general primer/type-specific primer polymerase chain reaction system (GP/TS-PCR) after DNA extraction. Patients with incident and prevalent CIN 2/3 were similar with respect to age. By GP/TS-PCR carried out under suboptimal conditions due to DNA extraction, HPV DNA was detected in 69.4% (25 of 36) of smears from incident CIN 2/3 compared to 95% (38 of 40) in prevalent CIN 2/3 (P = 0.003). Using hybrid capture, smears of incident CIN 2/3 were HPV positive in 50% (18 of 36) compared to 80% (32 of 40) in prevalent CIN 2/3 (P = 0.006). High-risk HPVs were significantly less common in smears from incident CIN 2/3 compared with prevalent CIN 2/3: 36.1% vs 72.5% by GP/TS-PCR (P = 0.001) and 47.2% vs 80% by hybrid capture assay (P = 0.003), respectively. Virus load in HPV-positive smears of prevalent CIN 2/3 was significantly higher than of incident CIN 2/3 using semiquantitative PCR (P = 0.0005). Thus, high-risk HPV types were detected less frequently and in lower concentration in smears from incident CIN 2/3 than in smears from prevalent CIN 2/3.


Assuntos
Papillomaviridae/isolamento & purificação , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Adolescente , Adulto , Idoso , Sondas de DNA de HPV , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Papillomaviridae/genética , Reação em Cadeia da Polimerase , Prevalência , Fatores de Risco , Neoplasias do Colo do Útero/epidemiologia , Esfregaço Vaginal , Displasia do Colo do Útero/epidemiologia
12.
Obstet Gynecol Clin North Am ; 23(3): 657-73, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8869951

RESUMO

The sensitivity of cytology for detection of cervical intraepithelial neoplasia (CIN) is effectively augmented by cervicography with the disadvantage of lower specificity. However, the combination of cytology and cervicography can decrease the number of recalls, biopsies, and unnecessary treatments, which reduces cost. Down-staging of invasive cancer by visual inspection seems a cost-effective alternative to the introduction of cytology in countries with limited health facilities. Other methods such as speculoscopy, polarprobe, laser-induced fluorescence, computerized digital imaging colposcopy, or computer imaging have a potential to be used for future screening or triaging; however, so far, insufficient data are available to evaluate the validity of these techniques.


Assuntos
Neoplasias do Colo do Útero/diagnóstico , Colposcopia , Feminino , Fluorescência , Humanos , Processamento de Imagem Assistida por Computador , Lasers
13.
Am J Obstet Gynecol ; 174(5): 1534-41, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-9065125

RESUMO

OBJECTIVE: A commercial test for human papillomavirus detection (hybrid capture assay) was examined for its potential value to augment the sensitivity of cytologic study or cervicography for screening for cervical intraepithelial neoplasia grade 2/3. STUDY DESIGN: In a cohort of 967 women with a mean age of 37.1 years who underwent routine cytologic screening, cytologic examination, cervicography, and testing for high-risk human papillomavirus by the hybrid capture assay were compared for their ability to detect cervical intraepithelial neoplasia grade 2/3. Cervical punch biopsy specimens were taken in 20.5% (198/967) patients because they had an atypical or positive cervigram or abnormal cytologic results in the primary screening smears. The data were analyzed by two-tailed chi(2) and Fisher's exact test. RESULTS: Thirty-eight patients were diagnosed with cervical intraepithelial neoplasia grade 2/3 (prevalence 3.9%) by histologic study. Cytologic study identified 29%, cervicography 45%, and testing for high-risk human papillomavirus 50% of cervical intraepithelial neoplasia grade 2/3. When combined, detection of high-risk human papillomavirus or cervicography augmented sensitivity of cytologic study to 58% (p = 0.01) with positive predictive values of 23% and 17%, respectively. Results of the different techniques should be interpreted in relationship to each other and not as absolute values because collection of specimens for cytologic study was done with cotton swabs, which may be suboptimal for screening but is general practice in Germany. CONCLUSIONS: Screening for cervical intraepithelial neoplasia grade 2/3 can significantly be improved by human papillomavirus testing with the hybrid capture assay.


Assuntos
Programas de Rastreamento , Papillomaviridae/isolamento & purificação , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Adolescente , Adulto , Idoso , Envelhecimento/fisiologia , Biópsia , Feminino , Custos de Cuidados de Saúde , Humanos , Programas de Rastreamento/economia , Pessoa de Meia-Idade , Prevalência , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/epidemiologia , Esfregaço Vaginal , Displasia do Colo do Útero/epidemiologia
14.
Zentralbl Gynakol ; 118(12): 659-64, 1996.
Artigo em Alemão | MEDLINE | ID: mdl-9082702

RESUMO

Mammary serum antigen (MSA) serum levels were evaluated for its association with histopathologic outcome of breast biopsies. 212 women were undergoing a diagnostic extirpation for suspicious lesions of the breast. Invasive breast cancer was found in 24.5%, in-situ-carcinomas in 7.1% respectively. 56.1% of the women were diagnosed with proliferating benign breast diseases and normal breast tissue was found in 12.3% of the patients. In all women pretherapeutic MSA-serum levels were measured by Inhibition-ELISA using the monoclonal antibody 3E1.2. The positivity-rates of MSA, CA15-3, TPA and CEA were compared separately and in combination. MSA was positive in 25% of breast cancer patients when a cut-off level of 55 U/ml was applied. The addition of CA15-3, TPA or CEA increased the sensitivity to 42.3% and the increment of the positivity-rate was smaller by addition of CA15-3, when compared with TPA or CEA. The highest MSA serum levels and positivity-rates were associated with malignant tumours, but there was no significant difference compared with benign epithelial proliferations (19.5% positivity rate). The lowest positivity-rate was detected in mesenchymal proliferations of the breast (4.8%, p = 0.02). To sum up one can say that MSA serum levels do not allow to discriminate benign from malignant breast diseases and MSA is 2.5 to 3 times more sensitive for the prediction of early stages breast cancer compared to CA15-3, TPA and CEA.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Neoplasias da Mama/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Mama/patologia , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Diagnóstico Diferencial , Feminino , Doença da Mama Fibrocística/sangue , Doença da Mama Fibrocística/diagnóstico , Doença da Mama Fibrocística/patologia , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos , Sensibilidade e Especificidade
15.
Diagn Microbiol Infect Dis ; 23(4): 161-4, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9407223

RESUMO

The validity of human papillomavirus (HPV) detection using the hybrid capture assay (HCA) was compared with the polymerase chain reaction (PCR) in 38 patients with high-grade squamous intraepithelial lesions (HSILs). HCA and PCR showed 84% agreement for HPV detection. HCA missed a significant higher proportion of HSIL compared with PCR (21% vs. 5%; P = .04). Thus, the sensitivity of HCA should be increased before this test can be recommended for HSIL.


Assuntos
Carcinoma de Células Escamosas/virologia , Hibridização de Ácido Nucleico/métodos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase/métodos , Infecções Tumorais por Vírus/virologia , Displasia do Colo do Útero/virologia , DNA Viral/análise , Feminino , Humanos , Kit de Reagentes para Diagnóstico
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