ABSTRACT
BACKGROUND AND OBJECTIVE: The aim of the El Alamo project was to define the demographic and clinic characteristics, treatment and evolution of women with invasive breast cancer diagnosed in hospitals of the GEICAM group (Spanish Breast Cancer Research Group) between 1990 and 1993. PATIENTS AND METHOD: Data from 4,532 patients were included. Forms were completed according to the medical history of patients, and collected in the GEICAM scientific office, where they were added to a data base. RESULTS: 32 hospitals from 19 provinces and 11 regional communities participated in the study. Mean age of the 4,532 patients was 56.72 years, 1,428 (31.5%) were premenopausal and 2,988 (65.9%) were postmenopausal. Stage II tumors were most frequent (55.5%). Among patients with stage I, II and III at diagnosis, surgery was the first treatment in most (90.7%), radical mastectomy being the most frequent procedure performed (79.7%). 70.4% of 1941 patients with positive axillary node and 37.4% of 1,806 patients without axillary affection received adjuvant chemotherapy with or without hormone therapy. CONCLUSIONS: El Alamo project represents the largest data base on breast cancer in Spain and the results are similar to those observed in other countries such as the USA.
Subject(s)
Breast Neoplasms/epidemiology , Adult , Aged , Aged, 80 and over , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Female , Humans , Middle Aged , Spain/epidemiology , Survival RateABSTRACT
FUNDAMENTO Y OBJETIVO: El objetivo del proyecto "El Álamo" fue definir las características demográficas y clínicas, los tratamientos y la evolución de las mujeres diagnosticadas de cáncer de mama invasivo en hospitales del Grupo Español de Investigación en Cáncer de Mama entre los años 1990 y 1993. PACIENTES Y MÉTODO: Se incluyeron datos de 4.532 pacientes, recogidos entre diciembre de 1999 y diciembre de 2000. Los formularios completados a partir de las historias clínicas se incorporaron a una base de datos. RESULTADOS: En el estudio participaron 32 hospitales de 11 comunidades autónomas. La edad media de las 4.532 pacientes incluidas era de 56,72 años, de las que 1.428 (31,5 por ciento) eran premenopáusicas y 2.988 (65,9 por ciento) posmenopáusicas. Los tumores de estadio II fueron los más frecuentes (55,5 por ciento). Entre las enfermas con estadios I, II y III en el momento del diagnóstico, la cirugía fue el tratamiento de inicio de la mayoría (90,7 por ciento), siendo la mastectomía radical la intervención más frecuente (79,7 por ciento). El 70,4 por ciento de las 1.941 pacientes con ganglios axilares positivos y el 37,4 por ciento de las 1.806 sin afectación axilar recibieron quimioterapia adyuvante con o sin hormonoterapia. La mediana de supervivencia global de las 4.532 pacientes aún no se ha alcanzado. CONCLUSIONES: El proyecto "El Álamo" constituye una base de datos extensa sobre el cáncer de mama en España. La distribución por estadios en el momento del diagnóstico fue desfavorable respecto a la observada en otros países occidentales en el mismo período; sin embargo, los resultados terapéuticos por estadio son prácticamente similares (AU)
Subject(s)
Middle Aged , Adult , Aged , Aged, 80 and over , Female , Humans , Spain , Survival Rate , Breast NeoplasmsABSTRACT
Breast cancer (BCA) represents the highest incidence of death in 35- to 60-year-old women. Above all, hormone unresponsive BCA is still associated with poorer prognosis than hormone receptor expressing malign, mammary tumors. There is a consistent need for effective compounds to treat especially the first variant of this disease. Therefore, we investigated the cytotoxic effects of the marine polyether triterpenoid dehydrothyrsiferol (DT) in four BCA cell lines. Annexin V labeling revealed higher rates of DT-induced apoptosis in hormone insensitive than in estrogen receptor expressing cells. Flow cytometric analysis of combined DNA fragmentation and total DNA labeling allowed us to ascribe apoptotic cells to their cell cycle stage. Although, high cell mortality was detected in mitogen dependent G(1)-phase, time, concentration, and cell line dependent populations of apoptotic cells were also found to be of S-phase and G(2)/M-phase origin. These results suggest that the induction of apoptosis by DT might be transduced through more than one effector pathway. Cell cycle distributions and 5-bromo-2'-deoxyuridine incorporation varied in a treatment dependent manner and differed from control experiments with colchicine and doxorubicin which exclude that DT functions as a mitosis inhibitor. In summary, we propose that DT might be an interesting candidate for an antitumor drug development regimen.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis , Pyrans/pharmacology , Breast Neoplasms/pathology , Bromodeoxyuridine/metabolism , Camptothecin/pharmacology , Cell Cycle/drug effects , Cell Division/drug effects , Colchicine/pharmacology , DNA/biosynthesis , DNA/drug effects , Doxorubicin/pharmacology , Estrogens/metabolism , Humans , Phosphatidylserines/metabolism , Tumor Cells, CulturedABSTRACT
We had shown previously that the novel, marine, anticancer compound dehydrothyrsiferol (DHT) does not modulate P-glycoprotein (P-gp) dependent drug efflux. Many chemotherapeutics with clinical impact are substrates for the structurally distant related membrane transport protein MRP1 (multidrug resistance-associated protein 1). Thus, we were interested in analysing the behaviour of DHT and control compounds in specific drug transport of MRP1 overexpressing cells. We established a fluorescence based drug efflux system for specific, functional detection of interference of a test compound in MRP1 mediated drug extrusion. Briefly, MRP1 overexpressing HL60/Adr cells were incubated to uptake and then efflux fluorescent 5(6)-carboxyfluorescein diacetate (CFDA), rhodamine 123 (Rh123), or 3,3-diethylocarbocyanine iodide (DiOC2), respectively. Changes in cell fluorescence intensity after coincubation with the compound of interest were determined by flow cytometry. MRP1 mediated efflux of CFDA was analysed in the presence of DHT, the known substrates genistein, probenecid, and the specific inhibitor MK-571. To exclude unknown P-gp related interference in drug transport, efflux of the fluorescent P-gp substrate DiOC2 and specific inhibition by cyclosporin A (CsA) were analysed. Cytotoxicity of DHT in resistant HL60/Adr cells was found to be even superior to that in the parental HL60 leukaemia cell line. Consequently, DHT did not interfere in MRP1 mediated drug transport. In contrast to DiOC2, rhodamine 123 was not specifically effluxed by P-gp but also by MRP1. Therefore, we propose the MRP1 specific CFDA efflux model as a screening and/or excluding system for MRP1 substrates. Together with previous data our results suggest DHT to be an interesting candidate for further investigation directed towards a drug development regimen.
