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1.
Clin Cancer Res ; 26(21): 5682-5688, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32546648

RESUMO

PURPOSE: To assess the predictive value of molecular breast cancer subtypes in premenopausal patients with hormone receptor-positive early breast cancer who received adjuvant endocrine treatment or chemotherapy. EXPERIMENTAL DESIGN: Molecular breast cancer subtypes were centrally assessed on whole tumor sections by IHC in patients of the Austrian Breast and Colorectal Cancer Study Group Trial 5 who had received either 5 years of tamoxifen/3 years of goserelin or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Luminal A disease was defined as Ki67 <20% and luminal B as Ki67 ≥20%. The luminal B/HER2-positive subtype displayed 3+ HER2-IHC or amplification by ISH. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox models adjusted for clinical and pathologic factors. RESULTS: 185 (38%), 244 (50%), and 59 (12%) of 488 tumors were classified as luminal A, luminal B/HER2-negative and luminal B/HER2-positive, respectively. Luminal B subtypes were associated with poor outcome. Patients with luminal B tumors had a significantly shorter RFS [adjusted HR for recurrence: 2.22; 95% confidence interval (CI), 1.41-3.49; P = 0.001] and OS (adjusted HR for death: 3.51; 95% CI, 1.80-6.87; P < 0.001). No interaction between molecular subtypes and treatment was observed (test for interaction: P = 0.84 for RFS; P = 0.69 for OS). CONCLUSIONS: Determination of molecular subtypes by IHC is an independent prognostic factor for recurrence and death in premenopausal women with early-stage, hormone receptor-positive breast cancer but is not predictive for outcome of adjuvant treatment with tamoxifen/goserelin or CMF.See related commentary by Hunter et al., p. 5543.

2.
Eur J Cancer ; 127: 12-20, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31962198

RESUMO

PURPOSE: To investigate long-term results of patients with hormonal receptor-positive breast cancer treated with breast-conserving surgery (BCS) and consecutive endocrine therapy (ET) with or without whole breast irradiation (WBI). METHODS AND MATERIALS: Within the 8 A trial of the Austrian Breast and Colorectal Cancer Study Group, a total of 869 patients received ET after BCS which was randomly followed by WBI (n = 439, group 1) or observation (n = 430, group 2). WBI was applied up to a mean total dosage of 50 Gy (+/- 10 Gy boost) in conventional fractionation. RESULTS: After a median follow-up of 9.89 years, 10 in-breast recurrences (IBRs) were observed in group 1 and 31 in group 2, resulting in a 10-year local recurrence-free survival (LRFS) of 97.5% and 92.4%, respectively (p = 0.004). This translated into significantly higher rates for disease-free survival (DFS): 94.5% group 1 vs 88.4% group 2, p = 0.0156. For distant metastases-free survival (DMFS) and overall survival (OS), respective 10-year rates amounted 96.7% and 86.6% for group 1 versus 96.4% and 87.6%, for group 2 (ns). WBI (hazard ratio [HR]: 0.27, p < 0.01) and tumour grading (HR: 3.76, p = 0.03) were found as significant predictors for IBR in multiple cox regression analysis. CONCLUSIONS: After a median follow-up of 10 years, WBI resulted in a better local control and DFS compared with ET alone. The omission of WBI and tumour grading, respectively, were the only negative predictors for LRFS.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Braquiterapia/mortalidade , Neoplasias da Mama/tratamento farmacológico , Mastectomia Segmentar/mortalidade , Recidiva Local de Neoplasia/tratamento farmacológico , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Taxa de Sobrevida
3.
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
4.
Ann Surg Oncol ; 19(6): 1808-17, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22207051

RESUMO

PURPOSE: The number of removed axillary lymph nodes and the ratio of involved to removed lymph nodes are described as independent prognostic factors beside the absolute number of involved lymph nodes in breast cancer patients. The correlation between these factors and prognosis were investigated in trials of the Austrian Breast and Colorectal Cancer Study Group (ABCSG). METHODS: This retrospective analysis is based on the data of 7052 patients with endocrine-responsive breast cancer who were randomized in four trials of the ABCSG in the years 1990-2006 and underwent axillary lymph node dissection. The prognostic value of number of removed nodes (NRN), number of involved nodes (NIN), and ratio of involved to removed nodes (lymph node ratio, LNR) concerning recurrence-free survival and overall survival was analyzed. RESULTS: A total of 2718 patients had node-positive disease. No correlation was found between NRN and prognosis. Increasing NIN and LNR were significantly associated with worse recurrence-free survival and overall survival in univariate and multivariate analyses (P < .001). Only in the subgroup of patients with one to three positive lymph nodes and treated with mastectomy (n = 728) was LNR an additional prognostic factor in univariate and multivariate analyses. CONCLUSIONS: For breast cancer patients stringently medicated in the framework of prospective adjuvant clinical trials and requiring a mandatory minimum of removed nodes, NRN does not influence prognosis, and LNR is not superior to NIN as prognostic factor. In patients with one to three positive lymph nodes and mastectomy, LNR could play a role as an additional prognostic factor.


Assuntos
Neoplasias da Mama/patologia , Linfonodos/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
5.
Lancet Oncol ; 12(7): 631-41, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21641868

RESUMO

BACKGROUND: Analysis of the Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG-12) at 48 months' follow-up showed that addition of zoledronic acid to adjuvant endocrine therapy significantly improved disease-free survival. We have now assessed long-term clinical efficacy including disease-free survival and disease outcomes in patients receiving anastrozole or tamoxifen with or without zoledronic acid. METHODS: ABSCG-12 is a randomised, controlled, open-label, two-by-two factorial, multicentre trial in 1803 premenopausal women with endocrine-receptor-positive early-stage (stage I-II) breast cancer receiving goserelin (3.6 mg every 28 days), comparing the efficacy and safety of anastrozole (1 mg per day) or tamoxifen (20 mg per day) with or without zoledronic acid (4 mg every 6 months) for 3 years. Randomisation (1:1:1:1 ratio) was computerised and based on the Pocock and Simon minimisation method to balance the four treatment arms across eight prognostic variables (age, neoadjuvant chemotherapy, pathological tumour stage; lymph-node involvement, type of surgery or locoregional therapy, complete axillary dissection, intraoperative radiation therapy, and geographical region). Treatment allocation was not masked. The primary endpoint was disease-free survival (defined as disease recurrence or death) and analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00295646; follow-up is ongoing. FINDINGS: At a median follow-up of 62 months (range 0-114.4 months), more than 2 years after treatment completion, 186 disease-free survival events had been reported (53 events in 450 patients on tamoxifen alone, 57 in 453 patients on anastrozole alone, 36 in 450 patients on tamoxifen plus zoledronic acid, and 40 in 450 patients on anastrozole plus zoledronic acid). Zoledronic acid reduced risk of disease-free survival events overall (HR 0.68, 95% CI 0.51-0.91; p=0.009), although the difference was not significant in the tamoxifen (HR 0.67, 95% CI 0.44-1.03; p=0.067) and anastrozole arms (HR 0.68, 95% CI 0.45-1.02; p=0.061) assessed separately. Zoledronic acid did not significantly affect risk of death (30 deaths with zoledronic acid vs 43 deaths without; HR 0.67, 95% CI 0.41-1.07; p=0.09). There was no difference in disease-free survival between patients on tamoxifen alone versus anastrozole alone (HR 1.08, 95% CI 0.81-1.44; p=0.591), but overall survival was worse with anastrozole than with tamoxifen (46 vs 27 deaths; HR 1.75, 95% CI 1.08-2.83; p=0.02). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw. Bone pain was reported in 601 patients (33%; 349 patients on zoledronic acid vs 252 not on the drug), fatigue in 361 (20%; 192 vs 169), headache in 280 (16%; 147 vs 133), and arthralgia in 266 (15%; 145 vs 121). INTERPRETATION: Addition of zoledronic acid improved disease-free survival in the patients taking anastrozole or tamoxifen. There was no difference in disease-free survival between patients receiving anastrozole and tamoxifen overall, but those on anastrozole alone had inferior overall survival. These data show persistent benefits with zoledronic acid and support its addition to adjuvant endocrine therapy in premenopausal patients with early-stage breast cancer. FUNDING: AstraZeneca; Novartis.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Adulto , Anastrozol , Antineoplásicos Hormonais/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nitrilas/uso terapêutico , Pré-Menopausa , Tamoxifeno/uso terapêutico , Resultado do Tratamento , Triazóis/uso terapêutico , Ácido Zoledrônico
6.
Clin Cancer Res ; 15(18): 5888-94, 2009 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-19723645

RESUMO

PURPOSE: Previously, we have shown that p27 may be a potential predictive biomarker for the selection of premenopausal women with early-stage hormone-responsive breast cancer for adjuvant endocrine therapy. The purpose of the present study was to assess the clinical relevance of p27 expression in postmenopausal hormone receptor-positive breast cancer patients who were treated with adjuvant tamoxifen therapy. EXPERIMENTAL DESIGN: We determined the expression of p27 by immunohistochemistry in the surgical specimens of breast carcinoma patients who had been enrolled in Austrian Breast and Colorectal Cancer Study Group Trial 06 and received tamoxifen for 5 years. Early relapse and death within the first 5 years of follow-up were analyzed using Cox models adjusted for clinical and pathologic factors. RESULTS: p27 expression was high (>70% p27-positive tumor cells) in 252 of 483 (52%) tumor specimens and was associated with favorable outcome of the patients. Women with high p27 expression had a significantly longer disease-free survival (adjusted hazard ratio for relapse, 0.22; 95% confidence interval, 0.11-0.42; P < 0.001) and overall survival (adjusted hazard ratio for death, 0.39; 95% confidence interval, 0.21-0.72; P = 0.002) as compared with women with low p27 expression. CONCLUSION: Low p27 expression independently predicts early relapse and death in postmenopausal women with early-stage, hormone receptor-positive breast cancer who received adjuvant tamoxifen for 5 years.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Inibidor de Quinase Dependente de Ciclina p27/biossíntese , Pós-Menopausa , Receptores de Progesterona/análise , Tamoxifeno/uso terapêutico , Idoso , Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Receptores de Progesterona/genética , Recidiva , Análise de Sobrevida , Taxa de Sobrevida , Tamoxifeno/administração & dosagem , Resultado do Tratamento
7.
N Engl J Med ; 360(7): 679-91, 2009 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-19213681

RESUMO

BACKGROUND: Ovarian suppression plus tamoxifen is a standard adjuvant treatment in premenopausal women with endocrine-responsive breast cancer. Aromatase inhibitors are superior to tamoxifen in postmenopausal patients, and preclinical data suggest that zoledronic acid has antitumor properties. METHODS: We examined the effect of adding zoledronic acid to a combination of either goserelin and tamoxifen or goserelin and anastrozole in premenopausal women with endocrine-responsive early breast cancer. We randomly assigned 1803 patients to receive goserelin (3.6 mg given subcutaneously every 28 days) plus tamoxifen (20 mg per day given orally) or anastrozole (1 mg per day given orally) with or without zoledronic acid (4 mg given intravenously every 6 months) for 3 years. The primary end point was disease-free survival; recurrence-free survival and overall survival were secondary end points. RESULTS: After a median follow-up of 47.8 months, 137 events had occurred, with disease-free survival rates of 92.8% in the tamoxifen group, 92.0% in the anastrozole group, 90.8% in the group that received endocrine therapy alone, and 94.0% in the group that received endocrine therapy with zoledronic acid. There was no significant difference in disease-free survival between the anastrozole and tamoxifen groups (hazard ratio for disease progression in the anastrozole group, 1.10; 95% confidence interval [CI], 0.78 to 1.53; P=0.59). The addition of zoledronic acid to endocrine therapy, as compared with endocrine therapy without zoledronic acid, resulted in an absolute reduction of 3.2 percentage points and a relative reduction of 36% in the risk of disease progression (hazard ratio, 0.64; 95% CI, 0.46 to 0.91; P=0.01); the addition of zoledronic acid did not significantly reduce the risk of death (hazard ratio, 0.60; 95% CI, 0.32 to 1.11; P=0.11). Adverse events were consistent with known drug-safety profiles. CONCLUSIONS: The addition of zoledronic acid to adjuvant endocrine therapy improves disease-free survival in premenopausal patients with estrogen-responsive early breast cancer. (ClinicalTrials.gov number, NCT00295646.)


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Difosfonatos/uso terapêutico , Gosserrelina/uso terapêutico , Imidazóis/uso terapêutico , Pré-Menopausa , Adulto , Anastrozol , Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Difosfonatos/efeitos adversos , Intervalo Livre de Doença , Quimioterapia Combinada , Antagonistas de Estrogênios/efeitos adversos , Antagonistas de Estrogênios/uso terapêutico , Feminino , Seguimentos , Humanos , Imidazóis/efeitos adversos , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Nitrilas/uso terapêutico , Receptores de Estrogênio/análise , Tamoxifeno/efeitos adversos , Tamoxifeno/uso terapêutico , Triazóis/efeitos adversos , Triazóis/uso terapêutico , Ácido Zoledrônico
8.
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
9.
Clin Cancer Res ; 14(6): 1767-74, 2008 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-18347178

RESUMO

PURPOSE: The objective of our study was to determine the clinical relevance of cyclin D1 expression in hormone receptor-positive breast cancer patients who were treated with tamoxifen-based therapy. EXPERIMENTAL DESIGN: We assessed expression of cyclin D1 in surgical specimens of breast carcinoma by means of immunohistochemistry. Patients had been enrolled in either Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 05 or ABCSG Trial 06 and received tamoxifen as part of their adjuvant treatment. Overall survival and relapse-free survival were analyzed with Cox models adjusted for clinical and pathologic factors. RESULTS: Cyclin D1 was expressed in 140 of 253 (55%) tumors of ABCSG Trial 05 and in 569 of 948 (60%) tumors of ABCSG Trial 06. Expression of cyclin D1 was associated with poor outcome in both cohorts. Overall survival was significantly shorter in patients with cyclin D1-positive tumors compared with patients with cyclin D1-negative tumors [adjusted hazard ratio (HR) for death (ABCSG Trial 05), 2.47; 95% confidence interval (95% CI), 1.08-5.63; P = 0.03; adjusted HR for death (ABCSG Trial 06), 1.78; 95% CI, 1.36-2.34; P < 0.0001]. Relapse-free survival was also shorter in patients with cyclin D1-positive tumors than in patients with cyclin D1-negative tumors [adjusted HR for relapse (ABCSG Trial 05), 2.73; 95% CI, 1.50-4.96; P = 0.001; adjusted HR for relapse (ABCSG Trial 06), 1.52; 95% CI, 1.14-2.04; P = 0.005]. CONCLUSION: Cyclin D1 expression is an independent poor prognostic factor in women with early-stage, hormone receptor-positive breast cancer who received adjuvant tamoxifen-based therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Ciclina D1/metabolismo , Tamoxifeno/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminoglutetimida/administração & dosagem , Neoplasias da Mama/diagnóstico , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Gosserrelina/administração & dosagem , Humanos , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Prognóstico , Receptores Citoplasmáticos e Nucleares/metabolismo , Recidiva , Tamoxifeno/administração & dosagem , Resultado do Tratamento
10.
Breast Cancer Res Treat ; 112(2): 309-16, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18080748

RESUMO

PURPOSE: To evaluate the impact that pre- and postoperatively administered chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF) and postoperative chemotherapy vs. postoperative chemotherapy alone have on long-term prognosis. PATIENTS AND METHODS: The ABCSG conducted a nationwide randomized phase III trial in high-risk endocrine non-responsive breast cancer patients comparing pre- and postoperative chemotherapy containing CMF as preoperative treatment vs. postoperative chemotherapy alone between 1991 and 1999. From 1996 the ABCSG-07 protocol was amended to also allow randomization of high-risk endocrine-responsive patients. Of 423 eligible patients with high-risk primary breast cancer, 203 patients were randomly assigned to preoperatively receive three cycles of CMF (cyclophosphamide, methotrexate, fluorouracil; 600/40/600 mg/m(2)) intravenously on day 1 and 8, while 195 patients received postoperative chemotherapy alone. In both groups, three cycles of CMF were given initially, and another three cycles of CMF were administered in node-negative patients, whereas node-positive patients received three cycles of EC (epirubicin, cyclophosphamide; 70/600 mg/m(2)). RESULTS: Overall response rate to preoperative chemotherapy with three cycles of CMF was 56.2%; complete pathological response was achieved in 12 patients (5.9%). Recurrence-free survival was significantly better in patients receiving chemotherapy postoperatively (HR 0.7, 0.515-0.955; P = 0.024). No survival difference was observed between the two therapy groups (HR 0.800, 0.563-1.136; P = 0.213). DISCUSSION: Preoperative chemotherapy with CMF has to be considered as insufficient in high-risk breast cancer patients. Delayed surgery and anthracycline-based chemotherapy result in shorter recurrence-free survival but not overall survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Neoplasias Colorretais/metabolismo , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/patologia , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Oncologia/métodos , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Resultado do Tratamento
11.
J Natl Cancer Inst ; 99(24): 1845-53, 2007 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-18073378

RESUMO

BACKGROUND: Clinical trial data have shown that among breast cancer patients who were disease free after 5 years of adjuvant treatment with tamoxifen, further extended treatment with the nonsteroidal aromatase inhibitor letrozole reduces breast cancer recurrence. We examined the efficacy and tolerability of extended adjuvant therapy with another aromatase inhibitor, anastrozole, for 3 years among women who had completed 5 years of adjuvant therapy. METHODS: Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 6a is an extension of ABCSG Trial 6, in which hormone receptor-positive postmenopausal patients received 5 years of adjuvant tamoxifen, with or without the aromatase inhibitor aminoglutethimide, for the first 2 years of therapy. For ABCSG Trial 6a, patients who were disease free at the end of Trial 6 were randomly assigned to receive either 3 years of anastrozole or no further treatment. Efficacy data were analyzed with the use of a Cox proportional hazards regression model with two-sided P values and Kaplan-Meier curves, and tolerability data were estimated using logistic regression analysis with odds ratios and 95% confidence intervals (CIs). RESULTS: ABCSG Trial 6a included 856 patients. At a median follow-up of 62.3 months, women who received anastrozole (n = 387) had a statistically significantly reduced risk of recurrence (locoregional recurrence, contralateral breast cancer, or distant metastasis) compared with women who received no further treatment (n = 469; hazard ratio = 0.62; 95% CI = 0.40 to 0.96, P = .031). Anastrozole was well tolerated, and no unexpected adverse events were reported. CONCLUSIONS: These data confirm the benefit of extending adjuvant tamoxifen therapy beyond 5 years with anastrozole compared with no further treatment. Further research is required to define the optimum length of extended adjuvant therapy and to investigate the possibility of tailoring this period to suit different disease types.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Nitrilas/uso terapêutico , Pós-Menopausa , Triazóis/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Aminoglutetimida/uso terapêutico , Anastrozol , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Áustria , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Nitrilas/administração & dosagem , Nitrilas/efeitos adversos , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Prospectivos , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Projetos de Pesquisa , Tamoxifeno/uso terapêutico , Resultado do Tratamento , Triazóis/administração & dosagem , Triazóis/efeitos adversos
12.
J Clin Oncol ; 25(15): 2012-8, 2007 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-17513805

RESUMO

PURPOSE: Preoperative (neoadjuvant) chemotherapy for operable breast cancer downstages tumors initially not suitable for breast-conserving surgery. A pathologic complete response (pCR) to neoadjuvant chemotherapy may be a surrogate for longer overall survival, but this beneficial effect remains to be established. This phase III trial evaluated whether doubling the number of cycles of neoadjuvant treatment increased the pCR rate. PATIENTS AND METHODS: Patients with biopsy-proven breast cancer (T1-4a-c, N+/-, M0; stage I to III) were eligible and randomly assigned to either three or six cycles of epirubicin 75 mg/m2 and docetaxel 75 mg/m2 on day 1 and granulocyte colony-stimulating factor on days 3 through 10 (ED+G), every 21 days. The primary end point was the pCR rate of the breast tumor. Secondary end points were pathologic nodal status after surgery and the rate of breast-conserving surgery. RESULTS: A total of 292 patients were accrued, and 288 patients were assessable for efficacy and safety. Groups were well balanced for known prognostic factors. Six cycles of ED+G, compared with three cycles, resulted in a significantly higher pCR rate (18.6% v 7.7%, respectively; P = .0045), a higher percentage of patients with negative axillary status (56.6% v 42.8%, respectively; P = .02), and a trend towards more breast-conserving surgery (75.9% v 66.9%, respectively; P = .10). Rates of adverse events were similar, and no patients died on treatment. CONCLUSION: Doubling the number of neoadjuvant ED+G cycles from three to six results in higher rates of pCR and negative axillary nodal status with no excess of adverse effects. Thus, six cycles of ED+G should be the standard neoadjuvant treatment for operable breast cancer if this combination is chosen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Axila/patologia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/secundário , Quimioterapia Adjuvante , Docetaxel , Epirubicina/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Estudos Prospectivos , Taxoides/administração & dosagem
13.
Acta Oncol ; 46(2): 208-13, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17453371

RESUMO

A phase II trial was performed to investigate the efficacy and tolerance of combined gemcitabine and liposomal doxorubicin +/- recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with chemotherapeutically pretreated metastatic breast cancer. Thirty-four patients were entered in this trial. Chemotherapy consisted of gemcitabine and liposomal doxorubicin +/- G-CSF. Twenty seven patients received this regimen as 2nd line therapy, five patients as 3rd line and two patients as 4th line therapy after having failed taxane- and/or anthracycline-based chemotherapy or other drug combinations. After a median of six courses, an overall response rate of 26% (9 PR in 34 enrolled patients) was observed; 14 patients had disease stabilization (41%), and eight (24%) progressed. Three patients were not evaluable for response due to anaphylaxis after the first course and protracted thrombocytopenia. The median TTP was 7.5 months, and median overall survival was 15 months. Myelosuppression was the most frequently observed toxicity. Non-haematological side effects were generally mild to moderate. Our data suggest that gemcitabine and liposomal doxorubicin +/- G-CSF is an effective and fairly well tolerated regimen for chemotherapeutically pretreated patients with advanced breast cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Doxorrubicina/análogos & derivados , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , Sobrevida , Resultado do Tratamento
14.
Int J Radiat Oncol Biol Phys ; 68(2): 334-40, 2007 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-17363187

RESUMO

PURPOSE: In women with favorable early breast cancer treated by lumpectomy plus tamoxifen or anastrazole, it remains unclear whether whole breast radiotherapy is beneficial. METHODS AND MATERIAL: Between January 1996 and June 2004, the Austrian Breast and Colorectal Cancer Study Group (ABCSG) randomly assigned 869 women to receive breast radiotherapy +/- boost (n = 414) or not (n = 417) after breast-conserving surgery (ABCSG Study 8A). Favorable early breast cancer was specified as tumor size <3 cm, Grading 1 or 2, negative lymph nodes, positive estrogen and/or progesterone receptor status, and manageable by breast-conserving surgery. Breast radiotherapy was performed after lumpectomy with 2 tangential opposed breast fields with mean 50 Gy, plus boost in 71% of patients with mean 10 Gy, in a median of 6 weeks. The primary endpoint was local relapse-free survival; further endpoints were contralateral breast cancer, distant metastases, and disease-free and overall survival. The median follow-up was 53.8 months. RESULTS: The mean age was 66 years. Overall, there were 21 local relapses, with 2 relapses in the radiotherapy group (5-y rate 0.4%) vs. 19 in the no-radiotherapy group (5.1%), respectively (p = 0.0001, hazard ratio 10.2). Overall relapses occurred in 30 patients, with 7 events in the radiotherapy group (5-y rate 2.1%) vs. 23 events in the no-radiotherapy group (6.1%) (p = 0.002, hazard ratio 3.5). No significant differences were found for distant metastases and overall survival. CONCLUSION: Breast radiotherapy +/- boost in women with favorable early breast cancer after lumpectomy combined with tamoxifen/anastrazole leads to a significant reduction in local and overall relapse.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia Segmentar , Nitrilas/uso terapêutico , Tamoxifeno/uso terapêutico , Triazóis/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anastrozol , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Prospectivos , Dosagem Radioterapêutica , Taxa de Sobrevida
15.
Lancet ; 366(9484): 455-62, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16084253

RESUMO

BACKGROUND: Tamoxifen has been the standard adjuvant treatment for postmenopausal women with hormone-responsive early breast cancer for more than 20 years. However, the third-generation aromatase inhibitor anastrozole has proven efficacy and tolerability benefits compared with tamoxifen when used as initial adjuvant therapy. We investigate whether women who have received a period of adjuvant tamoxifen would benefit from being switched to anastrozole. METHODS: We present a combined analysis of data from two prospective, multicentre, randomised, open-label trials with nearly identical inclusion criteria. Postmenopausal women with hormone-sensitive early breast cancer who had completed 2 years' adjuvant oral tamoxifen (20 or 30 mg daily) were randomised to receive 1 mg oral anastrozole (n=1618) or 20 or 30 mg tamoxifen (n=1606) daily for the remainder of their adjuvant therapy. The primary endpoint was event-free survival, with an event defined as local or distant metastasis, or contralateral breast cancer. Analysis was by intention to treat. FINDINGS: 3224 patients were included in analyses. At a median follow-up of 28 months, we noted a 40% decrease in the risk for an event in the anastrozole group as compared with the tamoxifen group (67 events with anastrozole vs 110 with tamoxifen, hazard ratio 0.60, 95% CI 0.44-0.81, p=0.0009). Both study treatments were well tolerated. There were significantly more fractures (p=0.015) and significantly fewer thromboses (p=0.034) in patients treated with anastrozole than in those on tamoxifen. INTERPRETATION: These data lend support to a switch from tamoxifen to anastrozole in patients who have completed 2 years' adjuvant tamoxifen.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Nitrilas/uso terapêutico , Tamoxifeno/uso terapêutico , Triazóis/uso terapêutico , Idoso , Anastrozol , Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Nitrilas/efeitos adversos , Pós-Menopausa , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Estrogênio/análise , Tamoxifeno/efeitos adversos , Triazóis/efeitos adversos
16.
Thromb Haemost ; 89(6): 1098-106, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12783124

RESUMO

Platelet count has been reported to have predictive value in various cancer entities. In the case of breast cancer, evidence about involvement of platelets is still incomplete. Our objective was to assess the influence of pretreatment thrombocytosis on survival and establish its prognostic relevance for breast cancer patients. We performed a retrospective, multivariate analysis of 4,300 patients with early-stage breast cancer. All subjects participated in one of five prospective, randomized, multicenter trials conducted by the Austrian Breast and Colorectal Cancer Study Group. Thrombocytosis was defined as a platelet count exceeding 400 G/L. Median follow-up was 52 months. Univariate and multiple Cox regression models were calculated for overall survival (OS), breast cancer-related survival and disease-free survival (DFS). Pretreatment thrombocytosis was observed in 161 patients (3.7%). Estimated median OS, breast cancer-related survival and DFS for patients with versus those without thrombocytosis was 71.0 versus 99.5, 72.0 versus 100.9, and 80.4 versus 88.4 months, respectively (p = 0.0054, p = 0.0095, p = 0.0199). A multiple Cox regression model including tumor and nodal status, grading, age, hormone receptor status and pretreatment thrombocytosis identified pretreatment thrombocytosis as an independent predictive factor for OS (p = 0.0064) and breast cancer-related survival (p = 0.0162). Multivariate analysis failed to identify pretreatment thrombocytosis as an independent risk factor for DFS (p = 0.1355). In our retrospective study, elevated platelet counts at time of diagnosis were associated with poor prognosis in breast cancer. We hypothesize that platelets may contribute to the pathophysiology of hematogenous metastasis.


Assuntos
Neoplasias da Mama/complicações , Neoplasias da Mama/mortalidade , Trombocitose/mortalidade , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Taxa de Sobrevida , Trombocitose/etiologia
17.
Ann Surg ; 237(4): 556-64, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12677153

RESUMO

OBJECTIVE: To confirm evidence that breast-conserving treatment (BCT) does not impair the prognosis in breast cancer patients as compared to mastectomy and to argue that it be regarded as the treatment of choice in stage I and II disease. SUMMARY BACKGROUND DATA: Scientifically, survival rates in breast cancer have been shown to be stage-dependent, but independent of the extent of surgical breast tissue removal, as long as the resection margins are free of tumor infiltration. METHODS: Between 1984 and 1997, six different trials conducted by the Austrian Breast & Colorectal Cancer Study Group accrued a total of 4,259 women with hormone-responsive disease. The authors selected and compared three patient groups (n = 3,316) according to pathologic stage, age, and the surgical procedure applied. RESULTS: Over this interval, the BCT rate in the premenopausal node-positive subgroup experienced a highly significant increase from 27.2% to 73.2% overall. In the group of postmenopausal node-negative patients, the BCT rate grew significantly by 37.3% to 77.3% in total. With an overall BCT rate growing from 22.5% to 56.8% in postmenopausal node-positive women, those presenting with T1 tumors saw a significant increase from 35.1% to 65.9%. Mortality and local recurrence rates proved stable or even decreased considerably over time and in all subgroups. CONCLUSIONS: The presented outcome of BCT rates, significantly improved over this 16-year period and in no way counterbalanced by higher local recurrence or death rates, reflects an excellent example of surgical quality control. BCT can safely be regarded as the standard of therapy for T1 and increasingly for T2 disease. Especially in multi-institutional adjuvant breast cancer trials, the highest priority should be given to breast-conserving procedures.


Assuntos
Neoplasias da Mama/cirurgia , Mastectomia/métodos , Mastectomia/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Áustria , Ensaios Clínicos como Assunto , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Pós-Menopausa , Pré-Menopausa , Fatores de Tempo
18.
J Clin Oncol ; 21(6): 984-90, 2003 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-12637461

RESUMO

PURPOSE: To determine whether the addition of aminoglutethimide to tamoxifen is able to improve the outcome in postmenopausal patients with hormone receptor-positive, early-stage breast cancer. PATIENTS AND METHODS: A total of 2,021 postmenopausal women were randomly assigned to receive either tamoxifen for 5 years alone or tamoxifen in combination with aminoglutethimide (500 mg/d) for the first 2 years of treatment. Tamoxifen was administered at 40 mg/d for the first 2 years and at 20 mg/d for 3 years. RESULTS: All randomized and eligible patients were included in the analysis according to the intention-to-treat principle. After a median follow-up of 5.3 years, the 5-year disease-free survival in the aminoglutethimide plus tamoxifen group was 83.6% versus 83.7% in the monotherapy group (P =.89). The corresponding data for overall survival at 5 years were 91.4% and 91.2%, respectively (P =.74). More patients failed to complete combination treatment (13.7%) because of side effects as compared to tamoxifen alone (5.2%; P =.0001). CONCLUSION: Aminoglutethimide given for 2 years in addition to tamoxifen for 5 years does not improve the prognosis of postmenopausal patients with receptor-positive, lymph node-negative or lymph node-positive breast cancer.


Assuntos
Aminoglutetimida/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Moduladores de Receptor Estrogênico/uso terapêutico , Pós-Menopausa , Tamoxifeno/uso terapêutico , Idoso , Aminoglutetimida/administração & dosagem , Aminoglutetimida/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Áustria , Neoplasias da Mama/química , Quimioterapia Adjuvante , Progressão da Doença , Esquema de Medicação , Moduladores de Receptor Estrogênico/administração & dosagem , Moduladores de Receptor Estrogênico/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Segunda Neoplasia Primária/etiologia , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Análise de Sobrevida , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Resultado do Tratamento
19.
J Clin Oncol ; 20(24): 4621-7, 2002 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-12488405

RESUMO

PURPOSE: Effective adjuvant treatment modalities in premenopausal breast cancer patients today include chemotherapy, ovariectomy, and tamoxifen administration. The purpose of Austrian Breast and Colorectal Cancer Study Group Trial 5 was to compare the efficacy of a combination endocrine treatment with standard chemotherapy. PATIENTS AND METHODS: Assessable trial subjects (N = 1,034) presenting with hormone-responsive disease were randomized to receive either 3 years of goserelin plus 5 years of tamoxifen or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Stratification criteria included tumor stage and grade, number of involved nodes, type of surgery, and steroid hormone receptor content. Relapse-free survival (RFS) was defined as time from randomization to first relapse, local recurrence, or contralateral incidence, and overall survival (OS) as time to date of death. RESULTS: With a 60-month median follow-up, 17.2% of patients in the endocrine group and 20.8% undergoing chemotherapy developed relapses. Local recurrences emerged in 4.7% and 8.0%, respectively. RFS and local recurrence-free survival differed significantly in favor of endocrine therapy (P =.037 and P =.015), with a similar trend observed in OS (P =.195). CONCLUSION: Overall, our data suggest that the goserelin-tamoxifen combination is significantly more effective than CMF in the adjuvant treatment of premenopausal patients with stage I and II breast cancer.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/terapia , Ciclofosfamida/uso terapêutico , Fluoruracila/uso terapêutico , Gosserrelina/administração & dosagem , Metotrexato/uso terapêutico , Pré-Menopausa , Tamoxifeno/administração & dosagem , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Feminino , Humanos , Recidiva Local de Neoplasia , Ovariectomia , Taxa de Sobrevida
20.
Clin Cancer Res ; 8(6): 1831-7, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12060624

RESUMO

PURPOSE: Hypoxia-inducible factor (HIF)-1alpha is a transcription factor that supports the adaptation of human cancer cells to hypoxia and is involved in various pathways supporting tumor growth and progression. The aim of this study was to determine the prognostic influence of HIF-1alpha expression in patients with advanced-stage breast cancer, evident by positive lymph nodes. EXPERIMENTAL DESIGN: Expression of HIF-1alpha was determined immunohistochemically in 206 patients with lymph node-positive breast cancer. Furthermore, the interrelationship of HIF-1alpha with p53 and HER-2 protein expression, estrogen receptor density, and survival was analyzed. Colocalization of p53 and HIF-1alpha proteins was analyzed by confocal laser scanning microscopy. RESULTS: Strong nuclear expression of HIF-1alpha by invasive cancer cells was found in 48 patients (23.3%), moderate expression was found in 74 patients (35.9%), and weak expression was found in 35 patients (17%); no expression was observed in 49 patients (23.8%). HIF-1alpha protein overexpression was associated with significantly shorter overall and disease-free survival time (P = 0.003 and P = 0.001, respectively; Cox regression analysis). No correlation of HIF-1alpha and HER-2 expression or estrogen receptor density was observed. CONCLUSIONS: This study shows that HIF-1alpha is an independent prognostic factor for an unfavorable prognosis in patients with lymph node-positive breast cancer. Our results indicate that patients with advanced-stage breast cancers might profit from future therapies targeting HIF-1alpha.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Fatores de Transcrição/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia , Técnicas Imunoenzimáticas , Linfonodos/patologia , Metástase Linfática , Microscopia Confocal , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Prognóstico , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Taxa de Sobrevida , Proteína Supressora de Tumor p53/metabolismo
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