Validación externa de un nomograma para predecir una subsecuente metástasis cerebral en pacientes con cáncer de mama metastásico / External validation of a nomogram to predict subsequent brain metastases in patient with metastatic breast cancer

Introducción: Graesslin et al. (JCO2002; 12:2032-37) desarrollaron un monograma para predecir una subsecuente metástasis cerebral en pacientes con cáncer de mama metastásico. Nuestro objetivo fue evaluar la capacidad predictiva de este monograma en nuestra población. Métodos: se incluyeron 327 pacientes con cáncer de mama unilateral sin metástasis cerebral como primer sitio de metástasis. Se calculó la probabilidad de recurrencia cerebral de cada paciente de acuerdo al monograma propuesto por Graesslin et al. La curva de la característica operativa del receptor (ROC) derivada del área bajo la curva (AUC) fue usada para cuantificar la capacidad predictiva del nomograma. Resultados: Con una mediana de seguimiento de 6.5 años, 51 pacientes desarrollaron metastásicos cerebral (15.6%). Con los 327 pacientes, construimos una curva ROC y el modelo predictivo tuvo una pobre discriminación con una AUC de 0.586 (IC 95%, 0.498 – 0.675). Conclusiones: El nomograma propuesto por Graesslin et al. Mostró una baja capacidad discriminativa para predecir una subsecuente metástasis cerebral en nuestros pacientes.

Introduction: Graesslin et al. (JCO2002; 12:2032-37) developed a nomogram to predict subsequent brain metastases in metastatic breast cancer. Our aim was evaluate the predictive ability of this nomogram in our population. Methods: We included 327 patients with unilateral breast cancer without brain metastases as first metastatic site. We calculated the probability of brain recurrence of each patient according to nomogram proposed by Graesslin et al. The receptor operation characteristic (ROC) curve derived from the area under the curve (AUC) was used to quantify the predictive capability of the nomogram. Results: With a median of follow up of 6.5 years, 51 patients developed brain metastases (15.6%). With the 327 patients, we constructed a ROC curve and the model had a poor discrimination with an AUC of 0.586 (CI95%, 0.498-0.675). Conclusions: The nomogram proposed by Graesslin et al. showed a low discriminative ability to predict a subsequent brain metastases in our patients.

Patrones clínicos de los tumores de mama de acuerdo a su fenotipo en la población peruana / Clinical patterns of breast tumors according to their phenotype in the Peruvian population

Introducción: La clasificación de los tumores de mama estuvo basada en características histológicas, mientras que variables clinicopatológicos eran usadas como factores predictivos del curso clínico de la enfermedad. Los estudios de los perfiles genéticos consiguieron una clasificación molecular mucho más exacta. El objetivo de este estudio fue evaluar los patrones clínicos y de recurrencia de los tumores de mama de acuerdo a su fenotipo determinado por inmunohistoquímica. Material y métodos:Evaluamos un cohorte de 1044 pacientes diagnosticados con cáncer de mama operable entre los años 2000-2002 diagnosticados y tratados en el Instituto Nacional de Enfermedades Neoplásicas. Los fenotipos fueron caracterizado por inmunohistoquímica en [RE+ y/o RP+, HER2+], triple negativo [RE-, RP-, HER2-] y HER2+ [HER2+, sin importar el estado de los receptores hormonales]. Se evaluó la significancia pronóstica del fenotipo. Resultados: En nuestros casos, el 519 (49.7%) presentaron tumores [RE+ y/o RP+, HER2-], 212 (20.3%) presentaron tumores triple negativo y 313 (30.0%) presentaron tumores HER2+. El 23.2% (242) de los casos presentaron recurrencia local o a distancia y el 22.5% (235) fallecieron. El fenotipo [RE+ y/o RP+, HER2+] mostró una frecuencia más elevada de metástasis ósea (38.9%), seguido del fenotipo HER2 (27.2%) y triple negativo(23.6%). El fenotipo triple negativo mostró una baja tendencia a producir metástasis hepática (1.8%) comparado con [RE+ y/o RP+, HER2+] y HER2+ (21.1% y 19.6%, respectivamente). Se encontraron diferencias entre fenotipos en la sobrevida libre de enfermedad (P=0.001) y sobrevida global (P=0.005) los riesgos relativos de recurrencia y muerte fueron tiempo dependientes. Conclusiones: El fenotipo triple negativo y HER2+ se comportan como tumores altamente agresivos. La determinación del fenotipo por inmunohistoquímica es una excelente herramienta del pronóstico del curso de la enfermedad.

Introduction: The classification of breast tumors was based on histologic features, while clinicopa-thologic variables were used as predictors of clinical course of the disease. Studies of genetic profiles obtained a more accurate molecular classification. The objective of this study was to evaluate the clinical patterns and recurrence of breast tumors according to their phenotype determined by immunohistochemistry. Material and methods: We evaluated a cohort of 1044 patients diagnosed with operable breast cancer diagnosed between 2000-2002 and treated at the Instituto Nacional de Enfermedades Neo-plasicas. The phenotypes were characterized by immunohistochemistry in [ER + and / or PR +, HER2+], triple negative [ER-, PR-, HER2-] and HER2 + [HER2 +, regardless of the status of hormone recep-tors]. We assessed significant prognostic phenotype. Results: In our cases, 519 (49.7%) had tumors [ER + and / or PR +, HER2-], 212 (20.3%) had triple-negative tumors and 313 (30.0%) had HER2 + tumors. 23.2% (242) of cases had local or distant recurrence and 22.5% (235) died. The phenotype [ER + and / or PR +, HER2 +] showed a higher frequency of bone metastasis (38.9%), followed by HER2 phenotype (27.2%) and triple negative (23.6%). The triple negative phenotype showed a low tendency to produce liver metastases (1.8%) compared with [ER + and / or PR +, HER2 +] and HER2 + (21.1% and 19.6%, respectively). Differences were found between phenotypes in disease free survival (P = 0.001) and overall survival (P = 0.005) relative risks of recurrence and death were time dependent. Conclusions: Triple negative phenotype and HER2 + tumors behave as highly aggressive. The determination of the phenotype by immunohistochemistry is an excellent tool for predicting the course of the disease.

Prognostic effect of hormone receptor status in early HER2 positive breast cancer patients.

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.

Breast cancer classification according to immunohistochemistry markers: subtypes and association with clinicopathologic variables in a peruvian hospital database.

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.

Clasificación del cáncer de acuerdo a marcadores por inmunohistoquímica: distribución de subtipos y asociación con variables clínico patológicas / Classification according to cancer markers by immunohistochemistry: distribution of subtypes and association with clinicopathologic variables

Antecedentes: El cáncer de mama es la segunda neoplasia más común entre las mujeres en Perú. La clasificación molecular ha demostrado ser la mejor variable pronóstica y predictiva. El objetivo de este estudio fue evaluar las diferencias en las características clínico-patológicas y la sobrevida global en los cuatro subtipos moleculares de cáncer de mama: Luminal A (RE+ y/o RP+, HER2-); Luminal B (RE+ y/o RP+, HER2+); Tipo Basal (RE-, RP-,HER2-) Y Her2/neu (RE-,RP-,HER2+). Métodos: Se revisaron las historias clínicas de 1198 pacientes diagnosticados de cáncer de mama y tratados en el Instituto Nacional de Enfermedades Neoplásicas (Lima, Perú) entre el 2000 y 2002. La evaluación de RE, RP y HER2 se realizó por inmunohistoquímica, en tejidos fijados en formol e incluidos en parafina; la sobrevida global se calculó mediante el método de Kaplan-Meier. La prueba de log-rank se utilizó para determinar la significación estadística. Resultados: De 1198 canceres de mama invasivos, 591 (49.3%) fueron Luminal A, 158 (13.2%) Luminal B,255 (21.3%) Tipo Basal y 194 (16.2%) HER2/neu. La media de edad en el momento del diagnóstico fue 51.5 años para Luminal A,49.6 para Luminal B;49.5 para el Tipo Basal y el 49.4 para HER2/neu. El subtipo HER2/neu mostró un mayor porcentaje de; ganglios linfáticos positivos (63.7%), casos enestadio III (42.3%) y casos en estadio IV (9.7%). El subtipo Basal presentó una mayor prevalencia de fenotipo histológico pobremente diferenciado (70.3%). La mediana de seguimiento fue de 60 meses. La Sobrevida Global de 5 años mostró diferencias significativas entre los cuatro grupos (p <0.0001). Los Luminal A tiene la mayor Sobrevida Global, seguido de los Luminal B, Tipo Basal y HER2. Comparamos nuestros resultados con estudios de otras poblaciones y encontramos que las frecuencias relativas de los subtipos moleculares de nuestros pacientes son similares a las reportadas por la población de Carolina del Norte.

Background: Breast Cancer (BC) is the second most common neoplasm among women in Perú. The molecular classification has shown to be the best prognostic and predictive variable. The aim of this study was to evaluate differences in the clinicopathologic features and the overall survival (OS) in the four BC molecular subtypes: Luminal A (ER+ and/or PR+, HER2-); luminal B (ER+ and/or PR+, HER2+); Basal cell like (ER-,PR-, HER2-) and Her2/neu (ER-,PR-,HER2+) Methods: We reviewed the clinical records of 1198 BC patients diagnosed and treated at the Instituto Nacional de Enfermedades Neoplásicas (Lima, Peru) from 2000 to 2002. Evaluation of ER, PR and HER2 was performed by IHC in formalin-fixed, paraffin-embedded tumor samples; OS was calculated using the Kaplan-Meier method. The log-rank test was used to examine the statistical significance. Results: Of 1198 invasive Be, 591 (49.3%) were luminal A, 158 (13.2%) luminal B, 255 (21.3%) basal like and 194 (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 cel llike and 49.4 for Her2. Her2 subtype showed the highest percentage of positive lymph nodes (63.7%), stage III cases (42.3%) and stage IV cases (9.7%). Basal Cell Like cases showed the highest prevalence of poorly differentiated phenotype (70.3%). The median follow-up was 60 months. The 5-year OS was different between the four groups (p<0.0001). Luminal A had the highest OS followed by Luminal B, Basal Cell like and the HER2. We compared our results with other populations and we found that the relative frequencies of molecular subtypes of our patients are similar to that reported by the population of North Carolina, but different from Southern Switzerland (Ticino)and the Polish population. Conclusions: This study shows that there are significant differences between the distribution of molecular subtypes of breast cancer and clinicopathologic features.

Identificación de pacientes con cáncer de mama en riesgo de metástasis al sistema nervioso central / Identifying breast cancer patients at risk for central nervous system metastases

Introducción.- Se han propuesto que ciertas sub poblaciones de pacientes con cáncer de mama tendrían un riesgo incrementado de desarrollar metástasis en el sistema nervioso central (SNC). El objetivo de este trabajo es describir factores de riesgo para metástasis en el SNC en pacientes portadoras de cáncer de mama. Pacientes y Métodos.- Se realizó una revisión retrospectiva de 1081 casos de cáncer de mama diagnosticados y tratados en el Instituto Nacional de Enfermedades Neoplásicas (Lima, Perú) durante los años 2000 al 2002, en estadios clínicos I, II, III o IV al momento del diagnóstico. La determinación de los marcadores: receptor de estrógeno, progesterona y Her2 se realizó por inmunohistoquímica. Se evaluó la incidencia acumulada de metástasis cerebrales de acuerdo a cada variable clínica o patológica. Resultados.- Un total de 1025 pacientes fueron diagnosticados en los estadios I, II o III. Dentro de este grupo 304 (29.7%) pacientes tuvieron una diseminación de la enfermedad local, regional o a distancia. Se identificaron un total de 56 pacientes con estadio IV, de los cuales 11 (19.6%) tuvieron metástasis al SNC en algún momento hasta la fecha del último control, mientras que 4 (7.1%) pacientes tuvieron en el SNC al diagnóstico. Se encontró relación significativa en términos de incidencia acumulativa entre primera metástasis al SNC y estado nodal, receptor de estrógeno, receptor de progesterona, Her2, sub tipo molecular y estadío clínico (P<0.01 para todas las variables). Conclusiones.- A pesar de observarse factores de riesgo significativos para el desarrollo de metástasis en el SNC, no se pueden discriminar aquellos pacientes que presentan alto riesgo de metástasis en el SNC.

Introduction.- It has been proposed that certain sub populations of breast cancer patients have an increased risk to develop central nervous system (CNS) metastases. The aim of this study is to describe risk factors to develop CNS metastases in breast cancer patients. Patients and Methods.- A retrospective review of 1081 cases of breast cancer patients with clinical stages I, II, III and IV was performed. Determination of estrogen and progesterone receptors and Her2 markers was done by immunohistochemistry. The accumulative incidence of CNS metastases was evaluated according to each clinico pathologic variable. Results.- A total of 1025 patients were diagnosed with breast cancer in stages I, II, III. In this group 304 (29.7%) had local, regional or distant disease. 56 patients were diagnosed with stage IV, in this group 11 (19.6%) had CNS metastases at some point until the date of last follow up, while 4 (7.1%) of patients had CNS metastases at diagnosis. There were significant differences in terms of accumulative incidence between CNS metastases and nodal status, estrogen receptor, progesterone receptor, Her2, molecular subtype, and clinical stage (P<0.01 for each variable). Conclusions.- Despite the observation of significant risk factors for the development of CNS metastases, it is not possible to determine those patients with high risk to develop CNS metastases.