ABSTRACT
BACKGROUND: Topoisomerase II-α is a molecular target of anthracyclines; several studies have suggested that topoisomerase II-α expression is related to response to anthracycline treatment. The objective of this study was to evaluate if topoisomerase II-α overexpression predicts response to anthracycline treatment in locally advanced breast cancer patients. MATERIAL AND METHODS: Topoisomerase II-α, HER2, estrogen receptor (ER) and progesterone receptor (PR) expression were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded breast tumors from 111 patients presenting with locally advanced breast cancer between 1995 and 2002. The prognostic value of these markers was analyzed using a multivariate proportional hazards regression model and an interaction analysis between topoisomerase II-α status and dose intensity. RESULTS: Tumors from 40 patients (36%) showed topoisomerase II-α overexpression, 62 patients (56%) for ER, 39 (35%) for PR and 26 (23%) for HER2. There were no significant correlations between topoisomerase II-α expression and response to therapy, progression-free survival (PFS) or overall survival (OS). Anthracycline dose intensity had a significant impact on PFS and OS in patients overexpressing topoisomerase II-α (P=0.010 and 0.027, respectively). Negative PR (P=0.041), positive HER2 (P=0.013) were identified as risk factors in the multivariate model. The multivariate analysis in patients topoisomerase II-α negative shown no significance (HR=0.92, IC 95% 0.39-2.15, P=0.839) while the multivariate analysis in topoisomerase II-α positive, dose intensity shown to be statistically significant (HR=2.725, IC 95% 1.07-6.95, P=0.036). CONCLUSIONS: Our data do not support a correlation between topoisomerase II-α expression in breast cancer patients and improved clinical benefit with anthracycline therapy. However, they do suggest that tumors overexpressing topoisomerase II-α may experience better clinical benefit with higher anthracycline dose intensity.
Subject(s)
Antigens, Neoplasm/analysis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/analysis , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , DNA Topoisomerases, Type II/analysis , DNA-Binding Proteins/analysis , Doxorubicin/administration & dosage , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/chemistry , Cyclophosphamide/administration & dosage , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Proportional Hazards Models , Receptor, ErbB-2/analysis , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: This study was conducted to determine the prognostic effect hormone receptor (HR) status in early HER2 positive (HER2+) breast cancer patients, since it has not yet been established whether HR status can be used in the prognosis of patients with (HER2+) breast cancer. PATIENTS AND METHODS: We obtained data from 299 patients with early HER2+ breast cancer who underwent surgery and received standard adjuvant chemotherapy, hormonal therapy and/or radiation between 2000 and 2002 at the Instituto Nacional De Enfermedades Neoplasicas, Perú. Clinical and pathological features were compared. Endpoints analyzed were disease free survival (DFS) and overall survival (OS). RESULTS: Overall, 155 patients were HR-positive (HR+) and 144 were negative (HR-). The two groups had similar characteristics except for histologic grade and extracapsular extension. With a median follow-up of 93 months, 5-year DFS was statistically different between the two groups: 65.0% for (HER2+/ HR-) and 74.6% for the (HER2+/ HR+) patients (p=.045). OS at 5 years was not statistically different between the two groups with 75.5% for (HER2+/ HR-) patients and 82.4% for the (HER2+/ HR+)(p=.140). CONCLUSIONS: Patients with (HER2+/ HR-) breast cancers treated with surgery and standard adjuvant chemotherapy exhibited a statistically worse DFS compared to those with (HER2+/ HR+) tumors. However, OS was similar in both groups.
Subject(s)
Breast Neoplasms/metabolism , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Adult , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Chemotherapy, Adjuvant , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Kaplan-Meier Estimate , Middle Aged , Neoplasm Staging , Outcome Assessment, Health Care/statistics & numerical data , Prognosis , Proportional Hazards Models , Radiotherapy , Receptor, ErbB-2/genetics , Retrospective StudiesABSTRACT
BACKGROUND: Molecular classification is an excellent prognostic and predictive method in breast cancer (BC). In this study. we evaluated differences in clinicopathologic features and overall survival (OS) in four BC molecular subtypes: luminal A, luminal B, basal cell-like, and HER2/neu. PATIENTS AND METHODS: Immunohistochemical evaluation of estrogen receptor (ER), progesterone receptor (PgR), and HER2 was performed using a Peruvian hospital database of 1198 BC patients who were diagnosed between 2000 and 2002. Overall survival was calculated. RESULTS: Out of 1198 patients with invasive BC, 49.3% were luminal A; 13.2%, luminal B; 21.3%, basal-like; and 16.2%, HER2. The mean of age at diagnosis was 51.5 years for luminal A; 49.6 for luminal B; 49.5 for basal-like; and 49.4 for HER2. The HER2 subtype showed 63.7% positive lymph nodes, 42.3% stage III and 9.7% stage IV cases. Basal subtypes showed the highest prevalence of a poorly differentiated phenotype (70.3%). Average follow-up was 60 months. Five-year OS was significantly different between all 4 groups (P < .0001); luminal A had the highest OS, followed by luminal B, basal-like; and HER2. Results are compared with other population studies. CONCLUSION: This study shows significant differences between the distribution of molecular subtypes and clinicopathologic features. Immunohistochemistry is useful in the clinical management of BC patients.
Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/classification , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Adult , Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Databases, Factual , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Middle Aged , Neoplasm Staging , Peru , Receptor, ErbB-2/biosynthesis , Receptor, ErbB-2/genetics , Receptors, Estrogen/biosynthesis , Receptors, Estrogen/genetics , Receptors, Progesterone/biosynthesis , Receptors, Progesterone/geneticsABSTRACT
Background: was to investigate the predictors of injection of the nipple areola complex in breast cancer patients to define the indications for mastectomy with immediate reconstruction preserving the skin and nipple areola complex, at Instituto Nacional de Enfermedades Neoplásicas. Methods: randomly reviewed 100 clinical records of patients diagnosed with breast cancer undergoing mastectomy, including patients with diagnosis in Instituto Nacional de Enfermedades Neoplasicas, excluding patients treated with surgery in another institution or tratmiento neoadjuvant chemotherapy or radiotherapy. Results: only 76 patients met the inclusion Criterior. The average age 47.32, the most common location in the breast was tunor the outer surface quadrants, the average distance from the nipple is 33,25 mm. .The average size of tumors is of 30.66 mm (range, 2 to 70 mm). The most common histological type is ductal cancer, 52 breast (68.4%). 25% of this undertaking paceintes nipple areola complex. Multicentricity correlate with the state of the nipple. Conclusions: We found a significant association between nipple areola commitment multicentricity.
Subject(s)
Humans , Adult , Female , Middle Aged , Mastectomy , Breast Neoplasms/surgery , NipplesABSTRACT
OBJETIVOS: Evaluar los resultados de las cirugías ambulatorias realizadas como manejo de cáncer de mama en el Instituto Nacional de Enfermedades Neoplásicas. MATERIALES Y MÉTODOS: Estudio retrospectivo, analítico, de una población de pacientes sometidas a cirugía mamaria por cáncer durante el año 2006 en el Departamento de Senos y Tumores Mixtos del Instituto Nacional de Enfermedades Neoplásicas, de las cuales 514 fueron sometidas a Mastectomía directa o Tumorectomía en forma hospitalizada. Se incluyen 207 pacientes que inicialmente tuvieron manejo ambulatorio. RESULTADOS: Del total de cirugías realizadas, el 25% fueron con anestesia local, 65.1% con anestesia general en forma ambulatoria y 9.9% en forma hospitalizada. El 33.3% de las pacientes tuvieron una sola cirugía, 53.6% tuvo 2 cirugías y 13.1% tuvieron 3 cirugías. La estancia hospitalaria, comparada con el año 1996, disminuyó de 7.7 a 5.3 días. Los tratamientos con anestesia local y hospitalización tuvieron costos aproximados de 126 y 928 soles respectivamente. CONCLUSIONES: El manejo ambulatorio puede ofrecer un ahorro sustancial. El manejo quirúrgico de las pacientes con cáncer de mama puede ser en su gran mayoría de forma ambulatoria y creemos que este puede ser reproducido en otras partes del país, disminuyendo la estancia hospitalaria y abaratando costos.
Subject(s)
Humans , Adult , Female , Young Adult , Middle Aged , Aged, 80 and over , Breast Neoplasms , Breast Neoplasms/surgery , Ambulatory Surgical Procedures , Analytical Epidemiology , Retrospective StudiesABSTRACT
PURPOSE: This phase II trial of pemetrexed explored potential correlations between treatment outcome (antitumor activity) and molecular target expression. EXPERIMENTAL DESIGN: Chemonaïve patients with advanced breast cancer received up to three cycles of pemetrexed 500 mg/m2 (10-minute i.v. infusion) on day 1 of a 21-day cycle, with folic acid and vitamin B12 supplementation. Tumors were surgically removed after the last cycle of pemetrexed as clinically indicated. Biopsies were taken at baseline, 24 hours after infusion in cycle 1, and after cycle 3. RESULTS: Sixty-one women (median age, 46 years; range, 32-72 years) were treated and were evaluable for response. Objective response rate was 31%. Simple logistic regression suggested a potential relationship between mRNA expression of thymidylate synthase (TS) and pemetrexed response (P = 0.103). Based on threshold analysis, patients with "low" baseline TS (< or = 71) were more likely to respond to pemetrexed than patients with "high" baseline TS (>71). Expression of baseline dihydrofolate reductase and glycinamide ribonucleotide formyl transferase tended to be higher in responders but this association was not significant (P > 0.311). TS expression increased significantly between baseline and biopsy 2 (P = 0.004) and dropped to near baseline levels at biopsy 3. Conversely, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase decreased after pemetrexed chemotherapy. CONCLUSIONS: Our results suggest a potential association between "low" pretreatment TS expression levels and response to pemetrexed chemotherapy. Future trials examining expression levels of other genes important to the folate pathway and/or breast cancer may identify a more robust multigene profile that can better predict response to this novel antifolate.
Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Glutamates/therapeutic use , Guanine/analogs & derivatives , Phosphoribosylglycinamide Formyltransferase/genetics , Tetrahydrofolate Dehydrogenase/genetics , Thymidylate Synthase/genetics , Adult , Aged , Breast Neoplasms/enzymology , Female , Guanine/therapeutic use , Humans , Middle Aged , Neoplasm Staging , Pemetrexed , Phosphoribosylglycinamide Formyltransferase/drug effects , RNA, Messenger/drug effects , RNA, Messenger/genetics , Tetrahydrofolate Dehydrogenase/drug effects , Thymidylate Synthase/drug effects , Treatment OutcomeABSTRACT
Objetivo: Se ha comparado el tratamiento estándar de conservación en cáncer de mama estadío clínico II (Tumorectomía + Disección Radical de Axila y Radioterapia a la Mama), con quimioterapia de inducción y tratamiento estándar, y un tercer tratamiento de quimioterapia de inducción + tumorectomía y disección radical de axila sin radioterapia a la mama. Este es un trabajo piloto de investigación clínica, prospectivo, randomizado eil 3 grupos de intervención, descriptivo y analítico. Materiales y Métodos: ingresaron al presente estudio 112 pacientes que fueron randomizados en los tres brazos con 41, 34, 37 pacientes respectivamente, la evaluación estadística demostró de que los tres brazos eran comparables. Se investigó respuesta clínica, radiológica y patológica a la quimioterapia neoadyuvante, así se comparó recurrencia local, sobrevida libre de enfermedad y sobrevida total con un seguimiento mínimo de 30 meses y máxima de 65 meses. Resultados y Conclusiones: La respuesta clínica a la quimioterapia fué: parcial 49.2 por ciento, completa 15,4 por ciento y en 35.2 por ciento no se obtuvo respuesta. La respuesta radiológica fue: parcial 45.6 por ciento y completa 19.5 por ciento. Desde el punto de vista anatomopatológico, en el 5.6 por ciento no se encontró neoplasia residual en la mama y en el 2.8 por ciento solo había carcinoma intraductal. La recurrencia local fue menor en las pacientes que tuvieron tratamiento de conservación estándar 7.3 por ciento si se compara con los brazos que tuvieron quimioterapia neodyuvante. Las pacientes que no tuvieron radioterapia a la mama recurrieron en el 48.3 por ciento de los casos. Tuvieron mayor recurrencia las pacientes en las que se encontró bordes infiltrados de tumor y metástasis axilar masiva (10 a más ganglios tomados). La sobrevida total y la sobrevida libre de enfermedad es similar en los tres brazos estudiados mediante curvas de Kaplan-Meyer.
Subject(s)
Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Mastectomy, Radical , Drug Therapy , Breast Neoplasms/surgery , Mastectomy, Segmental , Prospective Studies , Hospitals, State , Neoplasm Recurrence, Local , Clinical ProtocolsABSTRACT
El fluoruracilo (5-FU) ha sido asociado ocasionalmente a la ocurrencia de angina de pecho o infarto de miocardio. La frecuencia ha sido estimada en 1.6 por ciento, pero aumenta a 4.5 por ciento en los pacientes con historia previa de cardiomiopatía. Los estudios prospectivos monitorizando la administración de 5-FU con trazados electrocardiográficos han demostrado alteración hasta en 68 por ciento de pacientes. Se ha sugerido que la causa más probable de la angina y el infarto es el espasmo coronario. El cambio del esquema de administración diaria a semanal; el empleo de bloqueadores de los canales de calcio, y la administración de vasodilatadores coronarios han sido sugeridos para contrarrestar este efecto colateral indeseable del 5-fluoruracilo
Subject(s)
Humans , Male , Aged , Fluorouracil/adverse effects , Myocardial Ischemia/diagnosis , Myocardial Ischemia/etiology , Fluorouracil/administration & dosage , FluorouracilABSTRACT
Se reporta 11 casos de melanoma maligno de partes blandas (sarcoma de células claras) diagnosticados entre 1980 y 1992 en el Instituto Nacional de Enfermedades Neoplásicas (INEN). La edad de los pacientes estuvo entre 15 y 52 años. Predominó el sexo masculino (7 de 11 casos). La localización en todos los casos fue en la extremidad inferior y de preferencia en el pie (6 de 11 casos). La forma de presentación tumor en todos los casos y dolor en el 55 por ciento. El diagnóstico se hizo en base a los criterios de Enzinger en preparaciones de hematoxilina-eosina y se hizo tinciones especiales para anticuerpo melanoma específico (HMB-45) y proteína S-100. Siete pacientes tuvieron algún tratamiento previo. En el INEN el tratamiento fue amputación en 7 casos, resección local amplia en 2 casos, quimioterapia en un caso y ningún tratamiento adicional en un caso. Nueve pacientes fallecieron entre 2 y 49 meses, uno está vivo a los 24 meses y uno se perdió de vista. Se concluye que melanoma maligno de partes blandas tiene una baja incidencia, se presenta como tumor de crecimiento lento de localización preferente en extremidades inferiores, un número importante de casos se presenta con metástasis (6/11) al momento del diagnóstico, el tratamiento debería ser cirugía radical, por la frecuencia de recurrencias y considerar la disección ganglionar regional por la alta posibilidad de metástasis ganglionar. La mortalidad es alta.
