Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22
Filtrar
1.
N Engl J Med ; 385(5): 395-405, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34320285

RESUMO

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


Assuntos
Anastrozol/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Administração Oral , Idoso , Anastrozol/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Receptores de Estrogênio , Receptores de Progesterona , Tamoxifeno/uso terapêutico
2.
Br J Cancer ; 124(11): 1795-1802, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33762716

RESUMO

BACKGROUND: Preoperative chemotherapy containing anthracyclines and taxanes is well established in early-stage breast cancer. Previous studies have suggested that the chemotherapy sequence may matter but definitive evidence is missing. ABCSG trial 34 evaluated the activity of the MUC1 vaccine tecemotide when added to neoadjuvant treatment; the study provided the opportunity for the second randomisation to compare two different anthracycline/taxane sequences. METHODS: HER2-negative early-stage breast cancer patients were recruited to this randomised multicentre Phase 2 study. Patients in the chemotherapy cohort (n = 311) were additionally randomised to a conventional or reversed sequence of epirubicin/cyclophosphamide and docetaxel. Residual cancer burden (RCB) with/without tecemotide was defined as primary study endpoint; RCB in the two chemotherapy groups was a key secondary endpoint. RESULTS: No significant differences in terms of RCB 0/I (40.1% vs. 37.2%; P = 0.61) or pathologic complete response (pCR) rates (24.3% vs. 25%, P = 0.89) were observed between conventional or reverse chemotherapy sequence. No new safety signals were reported, and upfront docetaxel did not result in decreased rates of treatment delay or discontinuation. CONCLUSION: Upfront docetaxel did not improve chemotherapy activity or tolerability; these results suggest that upfront neoadjuvant treatment with anthracyclines remains a valid option.

3.
Eur J Cancer ; 132: 43-52, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32325419

RESUMO

BACKGROUND: Immune-based strategies represent a promising approach in breast cancer (BC) treatment. The glycoprotein mucin-1 (MUC-1) is overexpressed in more than 90% of BC patients, and is targeted by the cancer vaccine tecemotide. We have investigated the efficacy and safety of tecemotide when added to neoadjuvant standard-of-care (SoC) treatment in early BC patients. PATIENTS AND METHODS: A total of 400 patients with HER2-early BC were recruited into this prospective, multicentre, randomised 2-arm academic phase II trial. Patients received preoperative SoC treatment (chemotherapy or endocrine therapy) with or without tecemotide. Postmenopausal women with oestrogen receptor (ER)+++, or ER++ and Ki67 < 14%, and G1,2 tumours ('luminal A' tumours) received 6 months of letrozole. Postmenopausal patients with triple-negative, ER-/+/++ and Ki67 ≥ 14%, and with G3 tumours, as well as premenopausal patients, received four cycles of epirubicin/cyclophosphamide plus four cycles of docetaxel. Primary end-point was residual cancer burden (RCB; 0/I versus II/III) at surgery. Secondary end-points included pathological complete response (pCR), safety, and quality of life. FINDINGS: We observed no significant difference in RCB 0/I rates between patients with (36.4%) and without (31.9%) tecemotide in the overall study population (p = 0.40) nor in endocrine and chemotherapy-treated subgroups (25.0% versus 13.3%, p = 0.17; 39.6% versus 37.8%, p = 0.75, respectively). The addition of tecemotide did not affect overall pCR rates (22.5% versus 17.4%, p = 0.23), MUC-1 expression, or tumour-infiltrating lymphocytes content. Tecemotide did not increase toxicity when compared to SoC therapy alone. INTERPRETATION: Neoadjuvant tecemotide is safe, but does not improve RCB or pCR rates in patients receiving standard neoadjuvant therapy.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Vacinas Anticâncer/uso terapêutico , Glicoproteínas de Membrana/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Segurança do Paciente , Prognóstico , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
4.
Wien Klin Wochenschr ; 131(9-10): 233-236, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30887224

RESUMO

The working group recommends against contralateral prophylactic mastectomy (CPM) in women with breast cancer without a family history or genetic predisposition with unilateral breast cancer. This is based on the low risk of developing contralateral breast cancer, the lack of a survival benefit, the increased risk of surgical complications, and the lack of benefit on quality of life.


Assuntos
Neoplasias da Mama , Ginecologia , Obstetrícia , Mastectomia Profilática , Qualidade de Vida , Áustria , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Tomada de Decisão Clínica , Consenso , Feminino , Predisposição Genética para Doença , Humanos , Expectativa de Vida , Carga Tumoral
5.
Lancet Oncol ; 20(3): 339-351, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30795951

RESUMO

BACKGROUND: In postmenopausal women with hormone receptor-positive, early-stage breast cancer, treatment with adjuvant aromatase inhibitors is the standard of care, but it increases risk for osteoporosis and fractures. Results from the ABCSG-18 trial showed that use of denosumab as an adjuvant to aromatase inhibitor therapy significantly reduced clinical fractures. Disease-free survival outcomes from ABCSG-18 have not yet been reported. METHODS: Postmenopausal patients with early, hormone receptor-positive, non-metastatic adenocarcinoma of the breast, who had completed their initial adjuvant treatment pathway (surgery, radiotherapy, or chemotherapy, or a combination) and were receiving adjuvant aromatase inhibitors, were enrolled at 58 trial centres in Austria and Sweden into this prospective, double-blind, placebo-controlled, phase 3 trial. With permuted block randomisation (block sizes 2 and 4, stratified by previous aromatase inhibitor use, total lumbar spine bone mineral density score at baseline, and type of centre), patients were assigned (1:1) to receive subcutaneous denosumab (60 mg) or matching placebo every 6 months during aromatase inhibitor therapy. The primary endpoint (previously reported) was the time to first clinical fracture after randomisation. The secondary endpoint reported here is disease-free survival (defined as time from randomisation to first evidence of local or distant metastasis, contralateral breast cancer, secondary carcinoma, or death from any cause) in the intention-to-treat population. This study is registered with EudraCT (number 2005-005275-15) and ClinicalTrials.gov (number NCT00556374), and is ongoing for long-term follow-up. FINDINGS: Between Dec 18, 2006, and July 22, 2013, 3425 eligible patients were enrolled and randomly assigned; 1711 to the denosumab group and 1709 to the placebo group (with five others withdrawing consent). After a median follow-up of 73 months (IQR 58-95), 240 (14·0%) patients in the denosumab and 287 (16·8%) in the placebo group had disease-free survival events. Disease-free survival was significantly improved in the denosumab group versus the placebo group (hazard ratio 0·82, 95% CI 0·69-0·98, Cox p=0·0260; descriptive analysis, without controlling for multiplicity). In the denosumab group, disease-free survival was 89·2% (95% CI 87·6-90·8) at 5 years and 80·6% (78·1-83·1) at 8 years of follow-up, compared with 87·3% (85·7-89·0) at 5 years and 77·5% (74·8-80·2) and 8 years in the placebo group. No independently adjudicated cases of osteonecrosis of the jaw or confirmed atypical femoral fractures were recorded. The total number of adverse events was similar in the denosumab group (1367 [including 521 serious] adverse events) and the placebo group (1339 [515 serious]). The most common serious adverse events were osteoarthritis (62 [3·6%] of 1709 in the denosumab group vs 58 [3·4%] of 1690 in the placebo group), meniscus injury (23 [1·3%] vs 24 [1·4%]), and cataract (16 [0·9%] vs 28 [1·7%]). One (<0·1%) treatment-related death (due to pneumonia, septic kidney failure, and cardiac decompensation) occurred in the denosumab group. INTERPRETATION: Denosumab constitutes an effective and safe adjuvant treatment for patients with postmenopausal hormone receptor-positive early breast cancer receiving aromatase inhibitor therapy. FUNDING: Amgen.


Assuntos
Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Denosumab/administração & dosagem , Idoso , Inibidores da Aromatase/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Denosumab/efeitos adversos , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/efeitos dos fármacos , Modelos de Riscos Proporcionais , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética
6.
Lancet ; 386(9992): 433-43, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-26040499

RESUMO

BACKGROUND: Adjuvant endocrine therapy compromises bone health in patients with breast cancer, causing osteopenia, osteoporosis, and fractures. Antiresorptive treatments such as bisphosphonates prevent and counteract these side-effects. In this trial, we aimed to investigate the effects of the anti-RANK ligand antibody denosumab in postmenopausal, aromatase inhibitor-treated patients with early-stage hormone receptor-positive breast cancer. METHODS: In this prospective, double-blind, placebo-controlled, phase 3 trial, postmenopausal patients with early hormone receptor-positive breast cancer receiving treatment with aromatase inhibitors were randomly assigned in a 1:1 ratio to receive either denosumab 60 mg or placebo administered subcutaneously every 6 months in 58 trial centres in Austria and Sweden. Patients were assigned by an interactive voice response system. The randomisation schedule used a randomly permuted block design with block sizes 2 and 4, stratified by type of hospital regarding Hologic device for DXA scans, previous aromatase inhibitor use, and baseline bone mineral density. Patients, treating physicians, investigators, data managers, and all study personnel were masked to treatment allocation. The primary endpoint was time from randomisation to first clinical fracture, analysed by intention to treat. As an additional sensitivity analysis, we also analysed the primary endpoint on the per-protocol population. Patients were treated until the prespecified number of 247 first clinical fractures was reached. This trial is ongoing (patients are in follow-up) and is registered with the European Clinical Trials Database, number 2005-005275-15, and with ClinicalTrials.gov, number NCT00556374. FINDINGS: Between Dec 18, 2006, and July 22, 2013, 3425 eligible patients were enrolled into the trial, of whom 3420 were randomly assigned to receive denosumab 60 mg (n=1711) or placebo (n=1709) subcutaneously every 6 months. Compared with the placebo group, patients in the denosumab group had a significantly delayed time to first clinical fracture (hazard ratio [HR] 0·50 [95% CI 0·39-0·65], p<0·0001). The overall lower number of fractures in the denosumab group (92) than in the placebo group (176) was similar in all patient subgroups, including in patients with a bone mineral density T-score of -1 or higher at baseline (n=1872, HR 0·44 [95% CI 0·31-0·64], p<0·0001) and in those with a bone mineral density T-score of less than -1 already at baseline (n=1548, HR 0·57 [95% CI 0·40-0·82], p=0·002). The patient incidence of adverse events in the safety analysis set (all patients who received at least one dose of study drug) did not differ between the denosumab group (1366 events, 80%) and the placebo group (1334 events, 79%), nor did the numbers of serious adverse events (521 vs 511 [30% in each group]). The main adverse events were arthralgia and other aromatase-inhibitor related symptoms; no additional toxicity from the study drug was reported. Despite proactive adjudication of every potential osteonecrosis of the jaw by an international expert panel, no cases of osteonecrosis of the jaw were reported. 93 patients (3% of the full analysis set) died during the study, of which one death (in the denosumab group) was thought to be related to the study drug. INTERPRETATION: Adjuvant denosumab 60 mg twice per year reduces the risk of clinical fractures in postmenopausal women with breast cancer receiving aromatase inhibitors, and can be administered without added toxicity. Since a main side-effect of adjuvant breast cancer treatment can be substantially reduced by the addition of denosumab, this treatment should be considered for clinical practice. FUNDING: Amgen.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias da Mama/complicações , Fraturas Ósseas , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Aromatase/uso terapêutico , Áustria , Densidade Óssea/fisiologia , Neoplasias da Mama/tratamento farmacológico , Denosumab , Método Duplo-Cego , Feminino , Fraturas Ósseas/complicações , Fraturas Ósseas/prevenção & controle , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Suécia , Resultado do Tratamento
7.
Arch Gynecol Obstet ; 288(5): 1081-6, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23649464

RESUMO

PURPOSE: The extent of conization seems to influence the risk of preterm birth. The aim of this study was to compare the cone volume after surgical resection with large loop excision of the transformation zone (LLETZ) and cold knife conization (CKC). METHODS: The present retrospective multi-center study comprises 804 consecutive women, who underwent LLETZ (n = 412) or CKC (n = 392) between 2004 and 2009. Univariate and multivariable analyses were performed to compare cone volumes removed by LLETZ and CKC and identify independent risk factors for large cone volume. RESULTS: The median resected cone volume after LLETZ was significantly smaller [1.6 cm(3) (0.8-2.9)] than after CKC [2.1 cm(3) (1.4-3.5)] (<0.0001). Complete resection rates were comparable in both groups. Conization method, cone depth, and institution type were independent risk factors for removal of a large cone volume. CONCLUSION: CKC removes larger cone volumes than LLETZ without the advantage of higher complete resection rates.


Assuntos
Neoplasia Intraepitelial Cervical/cirurgia , Colo do Útero/cirurgia , Conização/métodos , Neoplasias do Colo do Útero/cirurgia , Adulto , Fatores Etários , Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Cuidados de Saúde Secundários , Centros de Atenção Terciária , Neoplasias do Colo do Útero/patologia
8.
Wien Klin Wochenschr ; 124(11-12): 412-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22739650

RESUMO

The current knowledge and recommendations on the clinical use of granulocyte colony-stimulating factors (G-CSF) in gynecologic cancers including breast cancer, along with the clinical experience of the members of the working group of the Austrian Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO), have been summarized. G-CSF is either administered as primary or secondary prophylaxis of febrile neutropenia. The term "primary prophylaxis" denotes the prophylactic use of G-CSF as early as during the first cycle of a new chemotherapeutic regimen. Secondary prophylaxis, on the other hand, defines the use of G-CSF after development of grade 4 neutropenia or febrile neutropenia in a preceding cycle of a particular chemotherapeutic regimen. When chemotherapy regimens are associated with a > 20 % risk of febrile neutropenia such as TAC (docetaxel-doxorubicin-cyclophosphamide), primary prophylaxis with G-CSF is indicated. When chemotherapy regimens are associated with a 10-20 % risk of febrile neutropenia, the decision for primary prophylaxis with G-CSF is based upon patient-related risk factors such as age > 65 years, previous cytotoxic treatment(s) and/or radiation therapy, preexisting tumor-related neutropenia or bone marrow involvement, preexisting neutropenia, infections/open sores, reduced Karnofsky performance status/WHO performance status and reduced nutritional status, advanced malignant disease, history of prior febrile neutropenia, impaired kidney function, and hepatic failure particularly with hyperbilirubinaemia. The patient's individual overall febrile neutropenia risk should be assessed prior to each chemotherapy cycle.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/prevenção & controle , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Femininos/prevenção & controle , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Oncologia/normas , Prevenção Primária/normas , Antineoplásicos/administração & dosagem , Antineoplásicos/normas , Áustria , Feminino , Fator Estimulador de Colônias de Granulócitos/normas , Humanos
9.
J Clin Oncol ; 30(7): 722-8, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-22271481

RESUMO

PURPOSE: Anastrozole (ANA) alone delivers significant disease-free survival benefits over tamoxifen (TAM) monotherapy in postmenopausal women with early estrogen receptor-positive breast cancer. The ABCSG-8 (Austrian Breast and Colorectal Cancer Study Group 8) study is a large phase III clinical trial addressing the sequence strategy containing ANA in comparison with 5 years of TAM in a low- to intermediate-risk group of postmenopausal patients. PATIENTS AND METHODS: Endocrine receptor-positive patients with G1 or G2 tumors were eligible. After surgery, patients were randomly assigned to 5 years of TAM or 2 years of TAM followed by 3 years of ANA. Adjuvant chemotherapy and G3 and T4 tumors were exclusion criteria. Intention-to-treat and censored analyses of on-treatment recurrence-free survival (RFS) were performed, and exploratory survival end points and toxicity were investigated. RESULTS: Information from 3,714 patients, including 17,563 woman-years, with a median of 60 months of follow-up was available for this analysis. Median age was 63.8 years, 75% were node negative, and 75% had T1 tumors. Sequencing of ANA after identical 2-year treatment with TAM in both arms did not result in a statistically significant improvement of RFS (hazard ratio [HR], 0.80; 95% CI, 0.63 to 1.01; P = .06). Exploratory analyses of distant relapse-free survival indicated a 22% improvement (HR, 0.78; 95% CI, 0.60 to 1.00). On-treatment adverse events and serious adverse events were consistent with known toxicity profiles of ANA and TAM treatment. CONCLUSION: Despite a low overall rate of recurrence in a population with breast cancer at limited risk of relapse, the a priori sequence strategy of 2 years of TAM followed by 3 years of ANA led to small outcome and toxicity benefits.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Nitrilas/uso terapêutico , Tamoxifeno/uso terapêutico , Triazóis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastrozol , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Áustria , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Nitrilas/administração & dosagem , Nitrilas/efeitos adversos , Estudos Prospectivos , Taxa de Sobrevida , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Triazóis/administração & dosagem , Triazóis/efeitos adversos
10.
Clin Cancer Res ; 17(18): 6012-20, 2011 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-21807638

RESUMO

PURPOSE: According to current guidelines, molecular tests predicting the outcome of breast cancer patients can be used to assist in making treatment decisions after consideration of conventional markers. We developed and validated a gene expression signature predicting the likelihood of distant recurrence in patients with estrogen receptor (ER)-positive, HER2-negative breast cancer treated with adjuvant endocrine therapy. EXPERIMENTAL DESIGN: RNA levels assessed by quantitative reverse transcriptase PCR in formalin-fixed, paraffin-embedded tumor tissue were used to calculate a risk score (Endopredict, EP) consisting of eight cancer-related and three reference genes. EP was combined with nodal status and tumor size into a comprehensive risk score, EPclin. Both prespecified risk scores including cutoff values to determine a risk group for each patient (low and high) were validated independently in patients from two large randomized phase III trials [Austrian Breast and Colorectal Cancer Study Group (ABCSG)-6: n = 378, ABCSG-8: n = 1,324]. RESULTS: In both validation cohorts, continuous EP was an independent predictor of distant recurrence in multivariate analysis (ABCSG-6: P = 0.010, ABCSG-8: P < 0.001). Combining Adjuvant!Online, quantitative ER, Ki67, and treatment with EP yielded a prognostic power significantly superior to the clinicopathologic factors alone [c-indices: 0.764 vs. 0.750, P = 0.024 (ABCSG-6) and 0.726 vs. 0.701, P = 0.003 (ABCSG-8)]. EPclin had c-indices of 0.788 and 0.732 and resulted in 10-year distant recurrence rates of 4% and 4% in EPclin low-risk and 28% and 22% in EPclin high-risk patients in ABCSG-6 (P < 0.001) and ABCSG-8 (P < 0.001), respectively. CONCLUSIONS: The multigene EP risk score provided additional prognostic information to the risk of distant recurrence of breast cancer patients, independent from clinicopathologic parameters. The EPclin score outperformed all conventional clinicopathologic risk factors.


Assuntos
Neoplasias da Mama/patologia , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Estimativa de Kaplan-Meier , Metástase Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Fatores de Risco
11.
Ann Surg Oncol ; 18(6): 1691-7, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21249455

RESUMO

BACKGROUND: Most patients with a positive sentinel lymph node (SN) have no further metastases in the axillary lymph nodes and may therefore not benefit from axillary lymph node dissection. In patients with melanoma, evaluation of the centripetal depth of tumor invasion in the SN, also known as the S classification of SN, and microanatomic localization of SN metastases were shown to predict non-SN involvement. This phenomenon has been less extensively studied in breast cancer. We sought to validate the S classification and microanatomic location of SN metastases in breast cancer patients with regard to their predictive value for non-SN involvement and overall survival (OS). METHODS: A total of 236 patients with positive SN followed by axillary lymph node dissection were reevaluated according to the S classification and the microanatomic location of SN (subcapsular, parenchymal, combined subcapsular and parenchymal, multifocal, extensive) metastases to predict the likelihood of non-SN metastases and OS. RESULTS: S classification and the microanatomic location of SN metastases were significantly correlated with non-SN status (P < 0.001). Especially patients with a maximum depth of invasion ≤0.3 mm (stage I according to the S classification) and those with SN metastases only in subcapsular location had a low probability of further non-SN metastases (7.8 and 6.1%) and a good prognosis for OS. CONCLUSIONS: S classification and microanatomic location of SN metastases predicts the likelihood of non-SN involvement. Especially patients with subcapsular or S stage I metastases have a low probability of non-SN metastases and a good prognosis for OS.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Linfonodos/patologia , Estadiamento de Neoplasias/classificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/mortalidade , Carcinoma Intraductal não Infiltrante/secundário , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Lobular/mortalidade , Carcinoma Lobular/secundário , Carcinoma Lobular/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Prospectivos , Biópsia de Linfonodo Sentinela , Taxa de Sobrevida , Adulto Jovem
12.
Wien Klin Wochenschr ; 122(21-22): 649-52, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21072604

RESUMO

The Calypso trial showed an improved progression-free survival with PEG-liposomal doxorubicin (PLD) and carboplatin (P) as compared with the standard regimen paclitaxel (PCLTX) and P in the second- or third-line treatment of platinum-sensitive epithelial ovarian cancer [1]. A panel of Austrian gynecologic oncologists discussed the clinical consequences of the data from the Calypso study for the routine practice. PLD + P had a significantly lower rate of alopecia and neuropathy than the taxane regimen, both toxicities which compromise the quality of life. Due to possible significant thrombocytopenia, the blood counts of patients undergoing PLD + P therapy should be monitored weekly. Patients receiving PLD/P are at higher risk of nausea and vomiting. Palmoplantar erythrodysesthesia (hand-foot syndrome) is a significant toxicity of PLD + P most prevalent after the third or fourth cycle. Prophylaxis consists of avoiding pressure on feet and hands and other parts of the body. Similarly, prophylaxis of mucositis seems important and includes avoiding consumption of hot, spicy and salty foods and drinks. Mouth dryness should be avoided. Premedication with antiemetics and dexamethasone dissolved in 5% glucose is done to prevent hypersensitivity to PLD. In conclusion, the therapeutic index is more favorable for PLD + P than for PCTX + P.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prova Pericial , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Áustria/epidemiologia , Carboplatina/uso terapêutico , Doxorrubicina/análogos & derivados , Doxorrubicina/uso terapêutico , Feminino , Humanos , Paclitaxel/uso terapêutico , Polietilenoglicóis/uso terapêutico , Prevalência , Análise de Sobrevida , Taxa de Sobrevida , Resultado do Tratamento
13.
Vaccine ; 28(43): 6997-7008, 2010 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-20732466

RESUMO

Group B streptococcus is one of the most important pathogens in neonates, and causes invasive infections in non-pregnant adults with underlying diseases. Applying a genomic approach that relies on human antibodies we identified antigenic GBS proteins, among them most of the previously published protective antigens. In vitro analyses allowed the selection of conserved candidate antigens that were further evaluated in murine lethal sepsis models using several GBS strains. In active and passive immunization models, we identified four protective GBS antigens, FbsA and BibA, as well as two hypothetical proteins, all shown to contribute to virulence based on gene deletion mutants. These protective antigens have the potential to be components of novel vaccines or targets for passive immune prophylaxis against GBS disease.


Assuntos
Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Proteínas de Transporte/imunologia , Streptococcus agalactiae/genética , Adulto , Animais , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Proteínas de Transporte/genética , Feminino , Deleção de Genes , Genômica , Humanos , Imunização Passiva , Camundongos , Mutação , Coelhos , Sepse/imunologia , Sepse/microbiologia , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/imunologia , Streptococcus agalactiae/patogenicidade , Virulência
14.
Int J Gynecol Cancer ; 19(1): 94-102, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19258949

RESUMO

OBJECTIVE: The Austrian Association for Gynecologic Oncology initiated in 1998 a prospective quality assurance program for patients with ovarian cancer. The aim of this study was to evaluate factors predicting overall survival especially under consideration of department volume. METHODS: All Austrian gynecological departments were invited to participate in the quality assurance program. A questionnaire was sent out that included birth date, histology, date of diagnosis, stage, and basic information on primary treatment. Description of comorbidity was not requested. Patient life status was assessed in a passive way. We did record linkage between each patient's name and birth date and the official mortality data set collected by Statistics Austria. No data were available on progression-free survival. Patients treated between January 1, 1999 and December 31, 2004 were included in the analysis. Mortality dates were available to December 31, 2006. Data were analyzed by means of classical statistical methods. Cut-off point for departments was 24 patients per year. RESULTS: A total of 1948 patients were evaluable. Approximately 75% of them were treated at institutions with fewer than 24 new patients per year. Patient characteristics were grossly similar for both department types. Multivariate analysis confirmed established prognostic factors such as International Federation of Gynecologists and Obstetricians (FIGO) stage, lymphadenectomy, age, grading, and residual disease. In addition, we found small departments (<24 patients per year) to have a negative effect on overall survival (hazards ratio, 1.38: 95% confidence interval, 1.2-1.7; and P < 0.001). CONCLUSIONS: The results indicate that in Austria, rules prescribing minimum department case load can further improve survival for patients with ovarian cancer.


Assuntos
Ginecologia/estatística & dados numéricos , Neoplasias Ovarianas/mortalidade , Garantia da Qualidade dos Cuidados de Saúde/estatística & dados numéricos , Áustria/epidemiologia , Feminino , Humanos
15.
Breast Cancer Res Treat ; 115(2): 373-80, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-18661231

RESUMO

BACKGROUND: Endocrine therapy is the preferred treatment in oestrogen- and/or progesterone-receptor (ER/PgR) positive breast cancer. Fulvestrant is a pure ER-antagonist. We present results from the Austrian Fulvestrant Registry. METHODS: Three-hundred and fifty patients were included. Time to progression (TTP) was defined as primary endpoint. A multivariate analysis was performed to identify factors significantly associated with TTP. RESULTS: Fulvestrant was administered as first-line therapy in 26%, second-line in 49%, and third-line or beyond in 25%. TTP was median 7 months. We observed a response in 15% of patients and 41% had SD > or = 6 months. First-line treatment and non-visceral metastases were associated with longer TTP. One case of pulmonary embolism was reported. Grade 3 toxicities consisted of joint pain (1.4%), nausea (1.4%) and hot flashes (0.3%). CONCLUSIONS: Fulvestrant was effective and well tolerated. TTP was superior to other trials, due to the large proportion of first-line patients. Activity is apparently independent of Her2-status.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Estradiol/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Áustria , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Estradiol/uso terapêutico , Feminino , Fulvestranto , Genes erbB-2 , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Sistema de Registros
16.
Clin Cancer Res ; 14(7): 2082-7, 2008 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-18381948

RESUMO

PURPOSE: To determine the effects of anemia on local relapse-free, relapse-free, and overall survival (LRFS, RFS, and OS, respectively) in premenopausal, primary breast cancer patients receiving adjuvant polychemotherapy, and to determine which conventional prognostic factors affected these outcomes. EXPERIMENTAL DESIGN: Four hundred twenty-four premenopausal patients with early-stage primary breast cancer and hormone receptor-expressing tumors were treated with i.v. cyclophosphamide/methotrexate/5-fluorouracil (CMF) polychemotherapy as part of an adjuvant phase III trial (Austrian Breast and Colorectal Cancer Study Group Trial 5). The influence of anemia (hemoglobin <12 g/dL) on LRFS, RFS, and OS was evaluated in a retrospective analysis. RESULTS: Of 424 patients, 77 (18.2%) developed anemia on CMF chemotherapy. After a median follow-up time of 5 years, 8.9% of nonanemic patients had local relapse compared with 19.6% of anemic patients (P=0.0006). Although mastectomy was associated with anemia (26% versus 13.7% in breast conserving surgery; P=0.002), multivariate analysis did not show mastectomy per se to be a significant risk factor for LRFS. Age, lymph node status, and hemoglobin had an independent significant influence on LRFS (P<0.005). Anemic patients had a relative risk of 2.96 (95% confidence interval, 1.41-6.23) for developing local relapse in comparison with nonanemic patients. CONCLUSION: Premenopausal breast cancer patients who developed anemia during the CMF regimen had significantly worse LRFS. In Austrian Breast and Colorectal Cancer Study Group Trial 5, anemia may have contributed to an almost doubled incidence of local recurrence in the chemotherapy arm. Molecular targets associated with tumor hypoxia and distinct from erythropoiesis should receive further attention in experimental and clinical settings.


Assuntos
Anemia/complicações , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/complicações , Neoplasias da Mama/mortalidade , Adulto , Anemia/epidemiologia , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pré-Menopausa , Prognóstico , Radioterapia
17.
J Med Screen ; 13(3): 148-51, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17007656

RESUMO

OBJECTIVES: The prevalence of self-reported participation and frequency of prostate cancer screening (digital rectal examination (DRE), prostate-specific antigen (PSA)) in Austrian men aged 40-79 years in the year 2005 is reported. METHODS: In a population-based cross-sectional study, a representative sample of 500 men was asked whether they ever had heard of early detection of prostate cancer by DRE or PSA test and, if so, whether they had ever had a prostate cancer screening test during their life, and if so the number of tests and the type of physician. RESULTS: Overall, the prevalence of self-reported prostate cancer screening was 55.8% (23.7% DRE only). The highest prevalence was observed in the age group of 60-69 years with 68.8% (28.1% DRE only). The highest prevalence of PSA tests was observed in the age group 70-79 years (40.9%). About 75% of the screening tests were performed by urologists. CONCLUSIONS: More than half of the target population (men aged 40-79 years) have had at least one prostate cancer screening test. Nearly one-third of men have already had one or more PSA tests. One-fifth of the PSA tests were requested by general practitioners or internists.


Assuntos
Programas de Rastreamento/estatística & dados numéricos , Neoplasias da Próstata/prevenção & controle , Adulto , Idoso , Áustria/epidemiologia , Exame Retal Digital , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue
18.
Acta Cytol ; 50(2): 185-90, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16610687

RESUMO

OBJECTIVE: To analyze factors in preoperative management and cytologic screening leading to a conization specimen free of neoplasia. STUDY DESIGN: From January 2001 through December 2003, cervical conization was performed on 208 consecutive cases at the Gynecologic Department, Krankenhaus Lainz, Vienna. Indications for cone biopsy were based on suspicious internal and/or external conventional cytologic screening results followed by punch biopsies in selected cases. RESULTS: Benign cervical lesions were diagnosed in 22 women (10.6%). Histologic results in negative cone biopsies were cervicitis (n = 12), infection with HPV without cervical intraepithelial neoplasia (n = 1), tubal metaplasia (n = 4) and combined diagnoses indicating no neoplasia (n = 5). Regarding cytologic screening results prior to conization, long-lasting infections with HPV can cause repeated findings of cells of unknown origin or reversible mild to moderate dysplasia eventually leading to conization specimens free of neoplasia. Furthermore, tubal metaplasia is a frequent pitfall in misinterpretation of cytologic smears. CONCLUSION: Reevaluation of cytologic screening results after the final histologic diagnosis becomes available following cone biopsy is a key issue in continuous quality assurance for the diagnostic procedure. In this article we also present a method of stratifying screening results according to the correctness of the results. Along with other established measures of diagnostic performance, this may support benchmarking and interpretation of the overall cytologic screening quality.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/patologia , Adulto , Idoso , Biópsia/métodos , Neoplasia Intraepitelial Cervical/virologia , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Garantia da Qualidade dos Cuidados de Saúde , Controle de Qualidade , Estudos Retrospectivos , Sensibilidade e Especificidade
19.
Acta Oncol ; 44(2): 129-33, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15788291

RESUMO

Tumour anaemia is a common symptom in cancer patients, particularly in those receiving chemotherapy. The aim of the current study was to analyse the impact of haemoglobin levels on the prognosis of patients with primary breast cancer receiving adjuvant chemotherapy. A total of 129 patients were available for analysis. The estimated median five-year overall survival rate was 76.6%. Mean Hb prior to primary surgery was 13.8 g/dl (SD 1.09), pre-chemotherapy Hb 12.8 g/dl (SD 1.2), and nadir Hb during chemotherapy 11.0 g/dl (SD1.1), respectively. Hb values were analysed as continuous variables in the Cox model. Survival analyses did not show a correlation between preoperative and pre-chemotherapy Hb levels with patient outcome. However, univariate analysis identified low nadir Hb (p=0.008), larger tumours (p=0.042), and hormone-receptor-negative tumours (p=0.022) to be significantly associated with poor patient survival. This result was persistent when analysis was adjusted for relevant prognostic factors in a multivariate Cox proportional hazards model. Nadir Hb, 1.54-fold increased risk for death (95% CI 1.03-2.32), and tumour size, 3.2-fold increased risk (95% CI 1.17-8.77) remained as independent variables, whereas hormone-receptor status failed to retain significance. The present data showed anaemia during adjuvant chemotherapy to be associated with poor survival in patients with primary breast cancer. Prospective randomized trials are warranted to examine the value of correcting anaemia with regard to improve disease control and survival.


Assuntos
Anemia/induzido quimicamente , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Tamoxifeno/efeitos adversos , Taxoides/efeitos adversos , Idoso , Anemia/complicações , Antineoplásicos/uso terapêutico , Áustria , Neoplasias da Mama/sangue , Neoplasias da Mama/cirurgia , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Quimioterapia Adjuvante , Feminino , Hemoglobinas/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida , Tamoxifeno/uso terapêutico , Taxoides/uso terapêutico , Fatores de Tempo
20.
Breast Cancer Res Treat ; 79(3): 347-53, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12846419

RESUMO

Anaemia is frequent in breast cancer patients but often remains undiagnosed and untreated. To determine the incidence of anaemia a prospective survey of primary non-metastatic breast cancer patients who received at least four cycles of adjuvant, non-platinum multi-agent chemotherapy was conducted at 47 centres in Austria. Two hundred and forty seven patients were prospectively included between October 1999 and December 1999. Haemoglobin (Hb) levels were determined after surgery and prior to each cycle of chemotherapy. Treatment of anaemia (blood transfusion or epoetin alfa) during the observation period was at the physician's discretion. For the purpose of this study, patients were considered to be anaemic if their Hb was below 12 g/dl. At baseline (after surgery and before the first cycle of chemotherapy), 28.7% of all patients were anaemic. The only significant differentiating factor was the type of surgery. 37.9% of patients who underwent mastectomy were anaemic, whereas only 22.8% of patients who underwent breast conserving surgery were anaemic. Forty two percent of 176 patients with a Hb level of > or = 12 g/dl at baseline developed anaemia during adjuvant chemotherapy. The only factor that significantly influenced the development of anaemia during chemotherapy was the Hb level at baseline. The total incidence of anaemia in patients with primary breast cancer who underwent surgery followed by adjuvant multi-agent chemotherapy was 58.7%. Forty nine patients (20.2%), 48 patients (19.2%) and 48 patients (19.2%) showed a decrease in Hb levels by 1 g/dl, 1-2 g/dl and > 2 g/dl, respectively. Only 18.6% of the patients who were found to be anaemic received anaemia treatment. The two most important factors for developing anaemia are the kind of surgery and the Hb level prior to chemotherapy.


Assuntos
Anemia/induzido quimicamente , Anemia/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Hemoglobinas/análise , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...