RESUMO
BACKGROUND: The protease uPA and its inhibitor PAI-1 play major roles in hemostasis and are also involved in cancer progression. This is mainly caused by their ability to degrade extracellular matrix-facilitating tumor cell migration. This study aimed to investigate the impact of uPA/PAI-1 and disseminated cytokeratin-positive cells (dCK+) on the outcome and the existence of synergistic effects. METHODS: We retrospectively analyzed a cohort of 480 breast cancer cases with known uPA/PAI-1 and dCK+ status. uPA/PAI-1 was tested on fresh tumor samples using a commercial ELISA test. Bone marrow aspirates were investigated immunocytochemically for CK18. RESULTS: DCK+ cells were identified in 23% of cases. uPA positivity was significantly associated with the occurrence of dCK+ cells (P = 0.028). uPA and PAI-1 were significantly associated with outcome in the subgroup of early-stage cases without chemotherapy. DCK+ cells alone were not prognostic. However, we found synergistic effects. In the subgroup of node-negative cases with and without chemotherapy, the prognostic impact of uPA and PAI-1 was enhanced in cases with additional dCK-positivity (triple +). In cases without chemotherapy, triple-positive status was independently prognostic (HR: 9.3 CI: 1.1-75) next to T stage. CONCLUSIONS: uPA and PAI-1 seem to influence the metastatic potential of dCK+ cells, which underlines its important role in tumor progression.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Queratinas/metabolismo , Células Neoplásicas Circulantes/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
We retrospectively investigated concordance of EndoPredict (EPclin) with urokinase plasminogen activator and plasminogen activator inhibitor-1 (uPA/PAI-1) in 72 breast cancer patients and compared the results with grading, molecular subtype and chemotherapy recommendation. Compared to uPA/PAI-1, EPclin proved to be more conservative concerning correlation with clinicopathological parameters and was significantly associated with the recommendation of adjuvant chemotherapy.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Regulação Neoplásica da Expressão Gênica , Inibidor 1 de Ativador de Plasminogênio/análise , Ativador de Plasminogênio Tipo Uroquinase/análise , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: HER-2/neu overexpression appears to be associated with improved response to anthracycline-based chemotherapy, but its association with response to taxane-based chemotherapy is unclear. In this retrospective subset analysis of patients with metastatic breast cancer enrolled in a randomized treatment trial, we investigated the response of patients with known HER-2/neu status to treatment with taxane-based epirubicin-paclitaxel (ET) chemotherapy compared with treatment with epirubicin-cyclophosphamide (EC) chemotherapy. METHODS: HER-2/neu status (positive [i.e., HER-2/neu amplification] or negative [i.e., no HER-2/neu amplification]) of archival specimens of primary tumors from 297 patients with metastatic breast cancer was determined by use of fluorescence in situ hybridization. Associations between HER-2/neu status and the efficacy of randomly assigned chemotherapy (ET versus EC) were investigated. All statistical tests were two-sided. RESULTS: Patients with HER-2/neu-positive tumors had a statistically significantly greater objective response rate than patients with HER-2/neu-negative tumors to treatment with ET (76% versus 50%, respectively; P =.005) but not to treatment with EC (46% versus 33%; P =.130). The objective response rate associated with ET was greater than that associated with EC for both HER-2/neu-positive tumors (76% versus 46%; P =.004) and HER-2/neu-negative tumors (50% versus 33%; P =.002). However, the improvement in the objective response rate associated with ET, compared with that associated with EC, was greater for patients with HER-2/neu-positive tumors (adjusted odds ratio [OR] = 3.64, 95% confidence interval [CI] = 1.48 to 8.92; P=.005) than for patients with HER-2/neu-negative tumors (adjusted OR = 1.92, 95% CI = 1.01 to 3.64; P=.046). Among patients with HER-2/neu-positive tumors, those who received ET had better progression-free survival and overall survival than those who received EC (for progression-free survival, adjusted relative risk [RR] = 0.65, 95% CI = 0.42 to 1.02; P=.062; for overall survival, adjusted RR = 0.60, 95% CI = 0.36 to 1.02; P=.059). However, among patients with HER-2/neu-negative tumors, those who received ET and those who received EC had similar progression-free survival and overall survival. CONCLUSIONS: HER-2/neu amplification does not adversely influence response to first-line chemotherapy with either ET or EC. Furthermore, a taxane-containing regimen such as ET may provide a preferential benefit to patients with HER-2/neu-positive tumors.