RESUMEN
BACKGROUND: Several studies in solid tumors have shown that expression of excision repair cross-complementation group 1 (ERCC1) and class III ß-tubulin (TUBB3) can predict response to chemoradiotherapy and might be prognostic factors. We assessed the role of ERCC1 and TUBB3 expressions as predictive and prognostic factors in locally advanced cervical squamous cell carcinoma (LACSCC) patients treated with different neoadjuvant regimens. METHODS: ERCC1 and TUBB3 were detected in 88 patients with LACSCC by immunohistochemical analysis. Sixty-two patients were included in 3 different prospective trials and grouped as follows: vinorelbine or docetaxel (group A, n = 44) and ifosfamide-vinorelbine-cisplatin (group B, n = 18). Both groups were compared with standard cisplatin chemoradiotherapy (group C, n = 26). Clinical data at baseline, disease-free survival (DFS) and overall survival (OS) were also collected. Univariate and multivariate Cox models were used to analyze the risk factors. RESULTS: Thirty-five patients (39.8%) and 18 (20.5%) had high ERCC1 and TUBB3 expression, respectively. Both proteins were overexpressed in tumors with unfavorable characteristics. High ERCC1 was associated with advanced FIGO stage (p = 0.034) and progressive disease (49% vs. 28%). Poor DFS (p = 0.021) and OS (p = 0.005) were observed in group C patients with high ERCC1 expression. Multivariate analysis showed that ERCC1 expression, FIGO stage and pretreatment hemoglobin level were significant prognostic factors (p = 0.002, p = 0.008 and p = 0.005, respectively). CONCLUSIONS: ERCC1 expression could be a predictive and prognostic factor in LACSCC patients who receive cisplatin monotherapy. Conversely, TUBB3 had no impact on survival in patients treated with antimicrotubule agents.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Proteínas de Unión al ADN/análisis , Endonucleasas/análisis , Proteínas de Neoplasias/análisis , Tubulina (Proteína)/análisis , Neoplasias del Cuello Uterino/metabolismo , Adulto , Anciano , Antineoplásicos Alquilantes/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Braquiterapia , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Ensayos Clínicos Fase II como Asunto , Proteínas de Unión al ADN/biosíntesis , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Endonucleasas/biosíntesis , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Histerectomía , Ifosfamida/administración & dosificación , Estimación de Kaplan-Meier , Mesna/administración & dosificación , Persona de Mediana Edad , Proteínas de Neoplasias/biosíntesis , Cuidados Paliativos , Pronóstico , Radioterapia Adyuvante , Tubulina (Proteína)/biosíntesis , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/terapia , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , VinorelbinaRESUMEN
Most cases of breast cancer are diagnosed at early stage of disease; therefore, treatment is oriented to increase the disease-free interval (DFI) and overall survival (OS). The prognosis, in comparison with other malignancies, has improved in the last decades as a result of mammographic screening. The aim of the study was to report the incidence of local and distant recurrence, DFI and OS in patients (pts) with stage I and stage II breast cancer over a period of 26 years divided into three groups. From January 1978 to December 2004, 927 women with early breast cancer (EBC) were included, 350 were stage I and 577 Stage II (AJCC 2002). Patients were divided according to the year of diagnosis into three periods of 10 years: Group A (1978-1987) 135 pts, Group B (1988-1997) 412 pts, and Group C (1998-2004) 380 pts. DFI was analyzed from the date of initial diagnosis to the date of local or distant recurrence. OS was estimated from the date of initial diagnosis to the last follow-up or date of death. Median age was 51 years (28-92). Conservative surgery was performed in 69% of pts, adjuvant radiation therapy in 78%, adjuvant chemotherapy in 29%, and adjuvant hormone therapy in 18%. The median follow-up was 8.4 years (0.3-30). The mean tumor size in Group A was 2.7 cm, in Group B 2.2 cm, and in Group C 1.94 cm (p = 0.0001). The percentage of pts with stage I increased from 13% in Group A to 38% in Group B and to 47% in Group C (p = 0.0001). Local recurrence was documented in 5% of all pts, whereas 28% developed metastatic disease. The DFI and OS showed a statistically significant difference among the three groups (p = 0.005). DFI rate at 5, 10, 15, 20, and 25 years was 71%, 67%, 65%, 65%, and 64%, respectively. OS at 5, 10, 15, 20, and 25 years was 82%, 62%, 49%, 39%, and 28%, respectively. Factors that had an effect in OS demonstrated by the multivariate regression analysis were: Tumor size, ER status, and nodal involvement (p < 0.001). Clinical outcomes in EBC in our experience are similar to those reported in international literature. The DFI and OS showed a statistically significant difference among the three groups. This group of pts continues to have a good prognosis as shown by the OS rate at 5, 10, 15, 20, and 25 years, although a high percentage of pts still to have recurrence and die from breast cancer after 5, 10, 15, 20, and 25 years of follow-up.