Cáncer de mama Her2-positivo: Terapias sistémicas actuales y experiencia local

El cáncer de mama (CM) es la primera causa de muerte por cáncer en mujeres tanto a nivel mundial como en Chile. Basados en características clínicas, histológicas y moleculares, múltiples estudios han identificado cuatro subtipos básicos de CM, los cuales están asociados a estrategias de tratamiento específicas y diferenciadas. El CM HER2-positivo representa un 15%-25% de todas las neoplasias mamarias y se caracteriza por su agresividad, recurrencia temprana y mayor tendencia a presentar compromiso del sistema nervioso central. En las últimas décadas, nuevas terapias dirigidas se han posicionado como el estándar de tratamiento y han cambiado la historia natural de esta enfermedad, transformándola en una enfermedad potencialmente curable incluso en etapas avanzadas. Esta revisión busca entregar un resumen de las bases biológicas de esta enfermedad. Por otro lado, dada la aparición de un creciente número de nuevas estrategias de manejo sistémico, nos proponemos revisar sus mecanismos de acción analizando reportes de datos clínicos publicados y la experiencia de nuestro grupo.

Breast cancer (BC) is the leading cause of cancer death for women both worldwide and in Chile. Based on clinical, histological, and molecular features, studies have identified four BC subtypes that correlate with treatment sensitivity. Human Epidermal growth factor Receptor type 2-positive (HER2+) BC represents 15%-25% of newly diagnosed breast neoplasms; HER2+ BC is characterized by its aggressive behavior, early recurrence, and higher risk of brain metastasis. In recent years, HER2-targeted therapies have become the mainstay of treatment and have redefined the natural history of this subtype, reducing relapse rates for early-stage patients and increasing survival in advanced-stage patients. Herein we review novel treatment strategies and their mechanisms of action, along with clinical and real-world data. We also provide a summary of currently available treatments for this subtype and our local experience regarding the management of this disease.

Cáncer de mama triple negativo: terapias sistémicas actuales y experiencia local / Triple negative breast cancer: current systemic therapy and local experience

Resumen El cáncer de mama (CM) es la principal causa de muerte por cáncer en mujeres chilenas. Es una enfermedad heterogénea, en la cual se han identificado cuatro subtipos básicos, determinados según características clínicas, histológicas y moleculares, los que se relacionan a estrategias terapéuticas. El CM triple negativo (CMTN) se caracteriza por su agresividad, recaída temprana y mayor tendencia a presentarse en etapas avanzadas. Frecuentemente afecta a mujeres jóvenes o con antecedentes familiares de CM u ovario. La única terapia sistémica aprobada para el CMTN es la quimioterapia; sin embargo, recientemente terapias moleculares con inhibidores de puntos de control inmune e inhibidores de la poli-adenosina difosfato ribosa polimerasa, han mostrado eficacia en pacientes seleccionados, y se han agregado al arsenal terapéutico para CMTN. Dada la aparición de estas nuevas estrategias, parece relevante entender la heterogeneidad de esta enfermedad, los mecanismos de acción de las nuevas terapias, resultados clínicos y criterios de selección de pacientes para terapias moleculares. Presentamos una revisión de la terapia sistémica actual del CMTN.

Breast cancer is the leading cause of cancer death in Chilean women and worldwide. It is a heterogeneous disease and four different subtypes have been identified based on clinical, histological and molecular features, which correlate with different treatment tumor sensitivity. Triple negative breast cancer is characterized by its aggressiveness, early relapse, and a greater tendency to present in advanced stages. It frequently affects young women, with cancer family history, especially breast or ovarian cancer. The approved systemic therapy for triple negative breast cancer is chemotherapy; however, recently, targeted therapies with checkpoint inhibitors and polyadenosine diphosphate ribose polymerase inhibitors have been shown to be effective in selected patients and have been added to the therapeutic arsenal for triple negative breast cancer. Given the appearance of these new strategies, it seems relevant to understand the heterogeneity of this disease, the mechanisms of action behind new therapies, clinical results, and the criteria to select patients for molecular therapies. We present a review of the current systemic therapy of this breast cancer subtype.

Linfoma anaplásico de células grandes asociado a implantes mamarios diagnosticado mediante punción por aguja fina. Caso clínico

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare type of non-Hodgkin T-cell lymphoma, recently defined in the 2016 World Health Organization (WHO) classification of lymphoid neoplasms. It occurs more commonly when textured implants are used and appears clinically as a late seroma. Cytologically, these lesions are composed of large atypical cells with pleomorphic nucleus and an immunophenotype positive for T cell markers and CD30, and negative for ALK1. We report a 56-years-old woman with breast implants who developed a periprosthetic seroma three years after surgery. A fine needle aspiration of the lesion was carried out. Cytology and the immunocytochemical study revealed cells compatible with BIA-ALCL. The flow cytometric study was negative. Excisional biopsy of the capsule was performed, observing that the neoplastic cells were confined to the inner surface of the capsule. Imaging studies did not find evidence of disseminated disease. The present case demonstrates the importance of the study of any late periprosthetic effusion, which can be performed using fine needle aspiration.

[Anaplastic large cell lymphoma associated with breast implants, diagnosed by fine needle aspiration. Report of one case]. / Linfoma anaplásico de células grandes asociado a implantes mamarios diagnosticado mediante punción por aguja fina. Caso clínico.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare type of non-Hodgkin T-cell lymphoma, recently defined in the 2016 World Health Organization (WHO) classification of lymphoid neoplasms. It occurs more commonly when textured implants are used and appears clinically as a late seroma. Cytologically, these lesions are composed of large atypical cells with pleomorphic nucleus and an immunophenotype positive for T cell markers and CD30, and negative for ALK1. We report a 56-years-old woman with breast implants who developed a periprosthetic seroma three years after surgery. A fine needle aspiration of the lesion was carried out. Cytology and the immunocytochemical study revealed cells compatible with BIA-ALCL. The flow cytometric study was negative. Excisional biopsy of the capsule was performed, observing that the neoplastic cells were confined to the inner surface of the capsule. Imaging studies did not find evidence of disseminated disease. The present case demonstrates the importance of the study of any late periprosthetic effusion, which can be performed using fine needle aspiration.

Cáncer de mama avanzado receptor de estrógeno positivo: manejo sistémico actual / Systemic therapy for estrogen receptor positive advanced breast cancer

El cáncer de mama es la primera causa de muerte por cáncer en mujeres chilenas. Mientras la mayoría de las personas logra curarse de esta enfermedad, un 5% de los casos se presenta inicialmente con enfermedad avanzada y hasta un 20-30% de pacientes con enfermedad localizada pueden sufrir recurrencias sistémicas. La mayoría de las neoplasias mamarias son dependientes del estímulo estrogénico, de allí que la deprivación de estrógenos es la principal estrategia terapéutica. Recientemente, el uso de terapias molecularmente dirigidas en combinación con la terapia endocrina ha logrado mejorar los resultados de sobrevida del cáncer de mama avanzado, con menos efectos colaterales que aquellos producidos por la quimioterapia convencional. El conocimiento de los mecanismos de acción de estas nuevas terapias, sus toxicidades, vías de resistencia y selección de pacientes para lograr los mejores beneficios terapéuticos son aspectos relevantes en el manejo de la enfermedad. Presentamos una revisión del estado actual del manejo del cáncer de mama metastásico hormonodependiente con enfásis en el uso de terapias endocrinas combinadas con terapias moleculares.

Breast cancer is the leading cause of cancer death in Chilean women. While most patientes are cured, five percent of cases present with advanced disease initially and up to 20-30% of patients with localized disease may suffer systemic recurrences. The majority of breast neoplasms are dependent on the estrogenic stimulus, hence the deprivation of estrogen is the main therapeutic strategy. Recently, the use of molecular targeted therapies in combination with endocrine therapy has been successful in improving the survival outcomes of advanced breast cancer, with fewer side effects than those produced by conventional chemotherapy. Knowledge of the mechanisms of action of these new therapies, their toxicities, resistance pathways and patient selection to achieve the best therapeutic benefits are relevant aspects in the management of the disease. We present a review of the current state of management of hormone-dependent metastatic breast cancer with emphasis on the use of endocrine therapies combined with molecular therapies.

Aplicación de tres modelos pronósticos en cáncer de mama precoz / Application of three prognostic models in T1N0M0 breast cancer

Resumen Objetivo Aplicar tres modelos pronósticos "online" (índice pronóstico de Nothingham (NPI), Adjuvantonline! (AO) y PREDICT utilizados en la práctica oncológica para estratificar a pacientes y definir el uso de terapias adyuvantes en pacientes con cáncer de mama (CM) precoz, para evaluar su correlación y predicción de sobrevida en nuestra población. Métodos Obtuvimos datos clínicos de pacientes con CM invasor T1N0M0, tratados en el Centro de Cáncer de la Pontificia Universidad Católica de Chile, Santiago, Chile, desde enero de 1997 hasta diciembre de 2003. Resultados Analizamos datos de 125 pacientes. Edad mediana fue 55 años (35-80). La mayoría de los tumores fueron carcinomas ductales infiltrantes (72,8%), receptor de estrógeno (RE) positivos (88,8%), 80% recibieron terapia endocrina (TE). El beneficio estimado de la TE y la quimioterapia (QT) en la sobrevida global (SG), determinadas según AO y PREDICT, no fueron significativamente diferentes (1,3% y 1% para QT, p = 0,13; 0,9% y 1% para TE, p = 0,8; respectivamente). El modelo NPI estimó una mediana de SG superior (96%) a la calculada por AO (90,9%) y PREDICT (92,5%). La mortalidad específica por CM fue de 3%, similar a lo observado (3,2%). La mediana de SG estimada por todos los modelos en el grupo de pacientes fallecidos no fue estadísticamente diferente al grupo de sobrevivientes (p = 0,85). Conclusión Los modelos pronósticos predicen apropiadamente la SG en pacientes con CM precoz; sin embargo, en esta serie, no discriminaron pacientes de mal pronóstico.

Objective Apply three prognostic models "online" (Nothingham index (NPI), Adjuvantonline! (AO) and PREDICT used in routine oncology practice in order to stratify patients and define the use of adjuvant therapies in patients with stage I breast cancer (BC) to evaluate its correlation and overall survival (OS) in our population. Methods We obtained patients' medical records data with invasive BC T1N0M0, treated at the Cancer Center of the Pontificia Universidad Católica de Chile, Santiago, Chile, from January 1997 to December 2003. Results We analyzed data from 125 patients. Median age was 55 years (35 80). Most tumors were infiltrating ductal carcinoma (72.8%), estrogen receptor positive (88.8%), 80% received endocrine therapy (ET). The estimated ET and chemotherapy benefit was not significantly different according to the AO and PREDICT models (1.3% and 1% for CT, p = 0.13, 0.9% and 1% for ET p = 0.8, respectively). The estimated median OS on NPI (96%) was higher than calculated by AO (90.9%) and PREDICT (92.5%). Interestingly disease specific mortality estimated was 3%, similar to that observed (3.2%). While the estimated median OS by all models in the group of deceased patients was lower than in surviving, this difference did not reach statistical significance (p = 0.85). Conclusion The prognostic models applied effectively predict OS in Chilean patients with T1N0M0 BC, but in this series, they do not sufficiently discriminate patients with poor prognosis. The addition of co -morbidities to AO does not alter the results.

Programa pionero de simulación en sutura para estudiantes de medicina de pregrado / A pioneer simulation curriculum of suture technique training for medical students

Introduction: Simulation has demonstrated utility in suture skills training on surgical residents. Objective: Evaluate validity of a simulated training curriculum of basic suture skills for medical students. Methods: Study conducted on 2013. Medical students were selected from the School of Medicine of Pontificia Universidad Católica de Chile (EMPUC). The program included four theoretical sessions and six practical sessions in order to training basic surgical tasks (five in total) on a simulated rubber model: one handed knot-tying, simple suture, vertical mattress suture, subcuticular interrupted suture and subcuticular running suture. A survey was applied to the participants to qualify each element of the program, on a scale of 1 to 7 (face-validity). One task (simple suture) was recorded on video, before and after training, to be evaluated by two experts on a blind fashion (content validity). Experts measure participant skills using an OSATS (Objective Structured Assessment of Technical Skills) and operative time. Statistical analysis for non-parametric variables, median and interquartile range, significant p-value < 0.05. Results: Thirty-six medical students participated, with assistance percentage was over 80 percent. Students qualified the experience favorably: simulated bench-model 6.0 [5.0-6.0], assistant-students 6.5 [6.0-7.0], practical sessions 7.0 [6.0-7.0], and general evaluation 6.5 [6.0-7.0]. In the evaluation of simple suture, there was a significant improvement on OSATS (10 [5-17] vs 19 [17-21]; p < 0.001) and decrease of operative time (138 seg [101-185] vs 77 seg [67-89]; p < 0.001) after training in every participant. Conclusion: This simulated curriculum delivers an alternative method for the development of technical competencies in medical students and could be incorporated on medical schools curricula.

Introducción: La simulación ha demostrado ser útil en la enseñanza de técnicas de sutura en cirujanos en formación. Objetivo: Evaluar la validez de un programa de entrenamiento simulado de técnica básica de sutura para estudiantes de pregrado de medicina. Material y Métodos: Estudio experimental realizado el año 2013, se seleccionó estudiantes de pregrado de la Escuela de Medicina de la Pontificia Universidad Católica de Chile (EMPUC). El programa incluye 4 sesiones teóricas y 6 prácticas, entrenando 5 tareas en modelo simulado de goma: nudo manual y puntos simple, Donati, intradérmico interrumpido e intradérmico continuo. Se entregó una encuesta a los participantes para calificar cada elemento del curso, en escala de 1 a 7 (validez de apariencia). Se grabó en vídeo una tarea (punto simple), pre y post entrenamiento, para ser evaluadas por 2 cirujanos en forma ciega (validez de contenido). Se utilizó escalas OSATS y medición de tiempo operatorio. Análisis estadístico para variables no paramétricas, mediana y rango interquartil, valor significativo p < 0,05. Resultados: Participaron 36 estudiantes, con un porcentaje de asistencia mayor a un 80 por ciento. Los alumnos calificaron favorablemente la experiencia: simulador de mesa 6,0 [5,0-6,0], ayudantes-alumnos 6,5 [6,0-7,0], clases prácticas 7,0 [6,0-7,0] y evaluación general 6,5 [6,0-7,0]. Respecto al punto simple, hubo mejoría significativa en OSATS (10 [5-17] vs 19 [17-21]; p < 0,001) y disminución de tiempo operatorio (138 seg [101-185] vs 77 seg [67-89]; p < 0,001) al finalizar el entrenamiento. Conclusión: Este programa simulado plantea un método alternativo para el desarrollo de competencias técnicas y podría ser incorporado en los currículos formales de las escuelas de medicina.

Cuándo y cómo realizar una biopsia de las lesiones cutáneas frecuentes: lo que el cirujano debe saber / How and when to perform a skin biopsy of a pigmented lesion: what the surgeon need to know

At present times, general surgeons are continuously faced to evaluate patients with pigmented lesions. Thus, is very important that surgeons acquire adequate knowledge not only to distinguish between suspicious lesion and non suspicious lesion, but also to correctly assess when and how to perform a skin biopsy. The early detection of melanoma and non melanoma skin cancer is one of the most important factors to achieve a better prognosis. The main objective of this article is to provide surgeons some tips and pitfalls to help accurate the evaluation and diagnosis of pigmented lesions. The authors also want to stress out the importance of the team work between surgeons and dermatologist, due that is well documented that multidisciplinary approach to skin cancer raises the possibilities of early diagnosis, adequate treatment and better results for patients with skin cancer.

En la actualidad, el cirujano continuamente se ve enfrentado a evaluar distintos tipos de lesiones cutáneas en los pacientes, por lo que debe tener conocimientos de las características que hacen que una lesión sea sospechosa o no, para evaluar correctamente cuándo y cómo realizar una biopsia de una lesión cutánea. El diagnóstico precoz, tanto del melanoma como del cáncer de piel no melanoma, ha demostrado ser clave para mejorar el pronóstico de nuestros pacientes. Este artículo pretende entregar algunas claves para afinar la evaluación y diagnóstico de las lesiones pigmentadas. Es muy importante también, recalcar la importancia del trabajo conjunto de los cirujanos con los dermatólogos, ya que la evaluación y manejo multidisciplinario mejora sustancialmente el diagnóstico, tratamiento y resultados de los pacientes con cáncer de piel.

Patología benigna de la mama / Benign breast disease

Las enfermedades benignas de la mama son mucho más frecuentes que las malignas y pueden representar un importante motivo de consulta para los especialistas en patología mamaria. La mayoría de las pacientes con patología mamaria benigna, dependiendo de su lugar habitual de control de salud, son evaluadas inicialmente por la matrona en su chequeo rutinario o por el médico general o familiar. Otras consultan a su ginecólogo y algunas pocas consultan de manera espontánea al especialista en enfermedades mamarias. Cualquiera de estos profesionales recibe a una paciente que, con frecuencia, está ansiosa por la posibilidad de alguna alteración maligna de la mama. Las unidades de patología mamaria se han ido organizando en un trabajo multidisciplinario, con una participación importante del radiólogo mamario. En este capítulo se mostrarán las principales enfermedades mamarias, ordenadas por los motivos de consulta más habituales, que son dolor mamario, nódulo mamario palpable, lesiones mamarias no palpables detectadas en exámenes radiológicos y en biopsias mamarias, secreción por el pezón y anomalías del desarrollo mamario.

Clinicopathologic subtypes and compromise of lymph nodes in patients with breast cancer.

UNLABELLED: Breast cancer (BC) is currently a heterogeneous disease with variations in clinical behaviour. Classification according to subtypes has allowed progress in the individualisation of treatment. The objective of this study is to evaluate the risk of axillary node compromise in patients with BC, according to clinicopathologic subtypes. Materials and methods are a retrospective, descriptive-analytical study. All patients that had undergone surgery for invasive BC were included, with the study of sentinel lymph nodes (SLNs) at Hospital Clínico de la Pontificia Universidad Católica, between May 1999 and December 2012. The results showed 632 patients fulfilled the inclusion criteria, with the median age being 55 years (range: 28-95), and 559 (88.4%) patients presented with estrogen receptor and/or progesterone receptor positive tumours. Luminal A: 246 patients (38.9%), luminal B: 243 (38.4%), luminal not otherwise specified: 70 (11.1%) triple negative (TN): 60 (9.5%) and over expression of epidermal growth factor type 2 receptor (HER2 positive): 13 (2.1%). Luminal tumours displayed a greater risk of metastasis in the SLNs, but this difference was not statistically significant (p = 0.67). TN and HER2 positive tumours presented the greatest proportion of metastatic compromise in non-sentinel lymph nodes (non-SLNs) (57.1% and 50%, respectively). The presence of macrometastasis (MAM) in the SLN was associated with a greater risk of compromise of the non-SLN. CONCLUSIONS: Luminal tumours are the most frequent and present a greater proportion of axillary lymph node compromise, without being statistically significant. TN and HER2 positive tumours tend to have a higher axillary compromise; however, this was not statistically significant in either. Only the presence of MAM in SLNs displayed a statistically significantly association in the compromise of non-SLNs.

[Survival of patients with metastatic breast cancer according to pathological types of tumors]. / Cáncer de mama metastásico: Caracterización de una cohorte según subtipos.

BACKGROUND: The prognosis of breast cancer (BC) is in part determined by the stage at diagnosis and its pathological characteristics. AIM: To evaluate the association between survival of women with metastatic breast cancer and pathological features of the tumor. PATIENTS AND METHODS: We obtained clinical and pathological data from patients diagnosed with a metastatic BC between 1999 and 2013. The expression of estrogen (ER) and progesterone (PR) receptors and human epidermal growth factor receptor 2 (HER2) was determined by immunohistochemistry. Clinicopathological subtypes were defined as: Luminal A: ER or PR positive, HER2 negative, histological grade (HG) 1 or 2; Luminal B: ER or PR positive, HER2 negative or positive or HG 3; triple negative (TN): ER, PR and HER2 negative, independent of the HG, positive HER2: ER, PR negative and HER2 positive, independent of HG. We analyzed survival based on these subtypes. RESULTS: We identified 54 patients aged 24 to 85 years, with metastatic BC at diagnosis. Seventy five percent had luminal tumors; 19.6% HER2 positive and 7.8% were TN. In 61% of evaluable tumors, HG was classified as 3. The frequency of HER2 positive and high HG tumors was greater in these patients with metastatic BC than in a non-metastatic local BC cohort. Survival was higher among patients with Luminal tumors than in women with non-Luminal cancer (56.4 and 11.4 months, respectively, p = 0.04). CONCLUSIONS: Patients with metastatic BC at diagnosis often had HER2 positive tumors and high HG. As in other studies, ER positive tumors had a better survival.

Características clínico-patológicas y sobrevida de pacientes con cáncer de mama bilateral sincrónico / Clinicopathological features and survival of patients with bilateral synchronous breast cancer

Introduction: Bilateral synchronous breast cancer (BSBC) has a variable incidence and conflicting data on prognosis. Our goal is to evaluate the characteristics and survival of patients with BSBC treated at Cancer Center of the Pontificia Universidad Católica de Chile. Patients and Methods: Descriptive study. We identified patients treated between January 1999 and May 2013. We evaluated and compared characteristics from BSBC patients with a local cohort of non-synchronous breast cancer. Results: The incidence of BSBC was 1.8 percent (n = 28). Three patients were excluded because of missing data. Therefore we analyzed 25 patients (50 tumors). Median age: 50 years (33-84). The dominant tumor's diagnosis was clinical in 47.6 percent of cases, and imaging in 90.5 percent of the contra-lateral non-dominant (p = 0.04). Average tumor size of invasive tumors was 2.5 cm for dominant tumor versus 1.7 cm for the non-dominant (p = 0.02). 81.4 percent of invasive tumors were estrogen receptor (ER) positive. Histological and subtype concordance between both tumors was 88 percent and 72 percent respectively. 54 percent of patients with BSBC were managed with total mastectomy versus 28.4 percent in the control group no BSBC (p = 0.0001). The estimated overall survival at 10 years was 76.5 percent in patients with no BSBC versus 62 percent in those with BSBC (p = 0.08). Conclusions: The BSBC is rare. Frequently they are ER positive tumors, mostly diagnosed through images and managed with less conservative surgery.

Introducción: La incidencia y pronóstico del Cáncer de mama (CM) bilateral sincrónico (CMBS), no son bien conocidos. Evaluamos las características y sobrevida de pacientes con CMBS tratadas en el Centro de Cáncer de la Pontificia Universidad Católica de Chile. Pacientes y Método: Estudio descriptivo. Identificamos pacientes con CMBS tratadas entre enero de 1999 y mayo de 2013. Evaluamos sus características y las comparamos con una cohorte local de CM no sincrónico. Resultados: La incidencia de CMBS fue de 1,8 por ciento (n = 28). Se excluyeron 3 pacientes por falta de datos. Analizamos por tanto, 25 pacientes (50 tumores). Mediana de edad: 50 años (33-84). El diagnóstico del tumor dominante fue clínico en el 47,6 por ciento de los casos, y por imágenes en 90,5 por ciento de los contra-laterales no dominantes (p = 0,04). Tamaño tumoral promedio de los tumores invasores fue de 2,5 cm en tumores dominantes vs 1,7 cm en los no dominantes (p = 0,02). Un 81,4 por ciento de los tumores invasores fueron receptor de estrógenos (RE) positivos. La concordancia histológica y de subtipo histológico entre ambos tumores fue de 88 por ciento y 72 por ciento respectivamente. Un 54 por ciento de las pacientes con CMBS fueron manejadas con mastectomía total versus un 28,4 por ciento en el grupo control de CM no BS (p = 0,0001). La sobrevida global estimada a 10 años fue de un 76,5 por ciento en pacientes con CM no BS versus 62 por ciento en aquellos con CMBS (p = 0,08). Conclusiones: El CMBS es poco frecuente. Usualmente son tumores RE positivos que reciben con menos frecuencia manejo conservador de la mama.

Cáncer de mama metastásico: Caracterización de una cohorte según subtipos / Survival of patients with metastatic breast cancer according to pathological types of tumors

Background: The prognosis of breast cancer (BC) is in part determined by the stage at diagnosis and its pathological characteristics. Aim: To evaluate the association between survival of women with metastatic breast cancer and pathological features of the tumor. Patients and Methods: We obtained clinical and pathological data from patients diagnosed with a metastatic BC between 1999 and 2013. The expression of estrogen (ER) and progesterone (PR) receptors and human epidermal growth factor receptor 2 (HER2) was determined by immunohistochemistry. Clinicopathological subtypes were defined as: Luminal A: ER or PR positive, HER2 negative, histological grade (HG) 1 or 2; Luminal B: ER or PR positive, HER2 negative or positive or HG 3; triple negative (TN): ER, PR and HER2 negative, independent of the HG, positive HER2: ER, PR negative and HER2 positive, independent of HG. We analyzed survival based on these subtypes. Results: We identified 54 patients aged 24 to 85 years, with metastatic BC at diagnosis. Seventy five percent had luminal tumors; 19.6% HER2 positive and 7.8% were TN. In 61% of evaluable tumors, HG was classified as 3. The frequency of HER2 positive and high HG tumors was greater in these patients with metastatic BC than in a non-metastatic local BC cohort. Survival was higher among patients with Luminal tumors than in women with non-Luminal cancer (56.4 and 11.4 months, respectively, p = 0.04). Conclusions: Patients with metastatic BC at diagnosis often had HER2 positive tumors and high HG. As in other studies, ER positive tumors had a better survival.

Impacto de las metástasis del linfonodo centinela y su tamaño, en el tratamiento del cáncer de mama / Impact of sentinel lymph node metastases in the treatment of breast cancer

Introducción: La importancia de las metástasis encontradas en linfonodos centinelas (LC) de pacientes con cáncer de mama ha sido cuestionada, por lo que frente al hallazgo de éstas, la observación sin disección axilar (DA), asociada a terapias adyuvantes, ha sido considerada como una alternativa en los últimos años. Objetivo: Evaluar las macro (MA), micro (MI) y submicrometástasis (SM) de cáncer de mama en LC, y su impacto en la DA posterior. Materiales y Métodos: Se revisaron los resultados de las biopsias de pacientes con cáncer de mama invasor con MA, MI y SM encontradas en el LC operadas en nuestra institución, entre mayo de 1999 y diciembre de 2011. Resultados: Se encontraron 134 pacientes con MA, 33 pacientes con MI y 30 SM, dentro de 632 pacientes con cáncer de mama invasor a los que se les realizó LC. De estos se operaron 130, 24 y 17 pacientes, respectivamente. La frecuencia de Linfonodos No Centinelas (LNC) con metástasis encontradas en la DA fue de 46,9 por ciento (61/130) para MA, 33,3 por ciento (8/24) para MI y 23,5 por ciento (4/17) para SM. Las metástasis del LNC provenientes de MA modificaron el TNM en 26,9 por ciento (35/130), las provenientes de MI en 20,8 por ciento (5/24) pacientes, mientras que las SM sólo lo modificaron en un paciente (5,9 por ciento). Conclusiones: La frecuencia del compromiso linfonodal en la DA es significativamente mayor en las pacientes con MA. El número de DA sin claro aporte terapéutico es alto y aumenta al disminuir el tamaño de las metástasis en el LC. Los resultados apoyan no realizar la DA en pacientes con MI y SM en el LC, que hayan recibido tratamiento quirúrgico conservador y vayan a recibir adyuvancia sistémica.

Introduction: The importance of sentinel lymph nodes (SL) metastasis at breast cancer patients has been questioned and observation without axillary dissection (AD) associated with adjuvant therapies has been the recommendation in recent years. Objective: To evaluate the macro (MA), micro (MI) and submicrometastasis (SM) of breast cancer in SL, and their impact on the posterior AD. Methods: We reviewed results of biopsies from patients with invasive breast cancer with MA, MI and SM found in the SL operated at our institution between May 1999 and December 2011. Results: We found 134 patients with MA, 33 patients with MI and 30 patients with SM, in a total of 632 patients with invasive breast cancer in those who underwent SL. These were operated 130, 24 and 17 patients respectively. The frequency of no sentinels lymph nodes (NSL) with metastases found on AD was 46.9% (61/130) for MA, 33.3% (8/24) for MI and 23.5% (4/17) for SM. The NSL metastasis from MA modified the TNM in 26.9% (35/130), those from MI in 20.8% (5/24) patients, while the SM only modified in one patient (5.9%). Conclusions: The frequency of lymph nodal involvement in AD is significantly higher in patients with MA. The number of AD without clear therapeutic input is high and increases with decreasing size of SL metastases. The results support to not perform AD in patients with MI and SM in the SL, who received conservative surgery and adjuvant therapy.

Cáncer de mama en mujeres adultas mayores, características clínicas e histopatológicas y resultados del tratamiento con intención curativa / Characteristics and results of breast cancer in elderly females treated with curative inten

Background: Aging is the main risk factor to acquire breast cancer (BC). Nevertheless BC in elderly patients is sub-represented in clinical trials. Aim: To describe the clinical characteristics and long term treatment results of localized BC in older women. Material and Methods: Review of medical records of 65 women aged 70 to 88 years, with localized BC, treated with surgery, postoperative radiotherapy or systemic therapy at a Clinical Hospital in Chile. Results: The presence of symptoms or abnormal findings on physical examination were the main reasons for consulting in 65% of cases. Compared with tumors detected on physical examination, those detected using screening mammogram were smaller and were in stage 1 with a higher frequency (18 and 59% respectively, p < 0.01). The pathological type was luminal in 80% of cases. Overall survival was better for luminal pathological type. All patients completed radiotherapy without interruptions developing minor acute toxicity. The most common co-morbidity was high blood pressure occurring in 46% of patients. Thirteen percent of patients had three or more co-morbidities. After a median follow up of 7 years, 23 (35%) patients had died and the cause of death was BC in 43% of cases. Two patients died of lung cancer. No patient had a local breast relapse. Conclusions: Screening mammogram in older women detected smaller tumors and it was associated with a better survival. BC is the ultimate cause of death in approximately half of cases.

Cáncer medular de tiroides: Experiencia quirúrgica en 10 años / Medullary thyroid cancer: Review of 28 patients

Background: Medullary thyroid cancer (MTC) represents approximately 5% of all thyroid cancers. Surgery is the only curative treatment, which includes total thyroidectomy and in most cases, neck dissection. Aim: To report our 10-year experience with surgical treatment of MTC. Material and Methods: Review of medical records and pathology reports of a university hospital. We retrieved data from 28 patients aged 47.2 ± 16 years (21 women) operated for a MTC treated between June 2002 and June 2012. Results: In 20 patients, MTC was diagnosed in the preoperative period. Total thyroidectomy was performed in all cases and included a neck dissection in 24 patients. Median follow-up was 48 (2-120) months. Twenty-five patients (89.2%) achieved complete remission of the disease and three had disease recurrence. There were no deaths during the follow up. Conclusions: The diagnosis of MTC is mainly based on cytology. Total thyroidectomy with neck dissection is the treatment of choice. An early-stage diagnosis is associated with low rates of recurrence and absence of mortality.

Rendimiento de la biopsia intraoperatoria por congelación en el estudio del linfonodo centinela en cáncer de mama / Intraoperative frozen section of the sentinel lymph nodes in breast cancer

Introduction: The sentinel lymph node (SN) biopsy has become the standard technique for staging the axillary involvement in breast cancer. The intraoperative diagnosis of lymph node metastatic involvement can immediately decide the need for axillary dissection. The main objective of this study was to determine the accuracy of intraoperative frozen section in the investigation of metastases in the SN, in patients with breast cancer, between 1999 and 2011. Materials and Methods: A retrospective study of patients operated for invasive breast cancer, in which the SN was studied with intraoperative frozen section. Results: 503 patients biopsy was performed with intraoperative frozen section. One hundred fifty-four (30.6 percent) patients had metastases in the SN, of these 103 (66.9 percent) were detected on frozen section. No significant difference in the ability to detect metastases for tumors up to 2 cm and tumors more than 2 cm was observed (p = 0.86). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of frozen section for detection of metastases in the SN was 66.9 percent, 99.7 percent, 99 percent and 87 percent, respectively. Conclusions: The accuracy of intraoperative biopsy for detection of metastases in the SN in our center is comparable to that described in the literature, being effective only for the investigation of macrometastases (MA). Given the low frequency of metastases in the SN in tumors up to 2 cm, associated with a relatively high number of micro (MI) and submicrometastasis (SM) and false negatives, it seems that in these tumors intraoperative biopsy is unnecessary.

Introducción: La biopsia del linfonodo centinela (LC) se ha convertido en la técnica estándar para estadificar el compromiso axilar en el cáncer de mama. El diagnóstico intraoperatorio del compromiso metas-tásico del linfonodo permite decidir en forma inmediata la necesidad de disección axilar. El objetivo general de este estudio fue determinar el rendimiento de la biopsia intraoperatoria por congelación en la pesquisa de metástasis en el LC, en pacientes con cáncer de mama, entre 1999 y 2011. Material y Métodos: Estudio retrospectivo de las pacientes operadas por cáncer de mama invasor, en que se realizó biopsia del LC, con estudio intraoperatorio por congelación. Resultados: 503 pacientes con biopsia del LC con estudio intrao-peratorio. Ciento cincuenta y cuatro (30,6 por ciento) pacientes tuvieron metástasis en el LC, de estos 103 (66,9 por ciento) fueron detectadas en la biopsia rápida. No hubo diferencias significativas en la capacidad de detección para los tumores de hasta 2 cm y los tumores mayores de 2 cm (p = 0,86). La sensibilidad, especificidad, valor predictivo positivo (VPP) y valor predictivo negativo (VPN) de la biopsia intraoperatoria para la detección de metástasis en el LC fue de 66,9 por ciento, 99,7 por ciento, 99 por ciento y 87 por ciento, respectivamente. Conclusiones: El rendimiento obtenido es comparable al descrito en la literatura, siendo efectiva sólo para la pesquisa de macrometástasis (MA). Dada la baja frecuencia de metástasis en el LC en tumores de hasta 2 cm, asociado a un número relativamente alto de micro (MI) y submicrometástasis (SM) y de falsos negativos, nos parece que, en estos casos, la utilización de la biopsia intraoperatoria del LC es innecesaria.

[Medullary thyroid cancer: review of 28 patients]. / Cáncer medular de tiroides: experiencia quirúrgica en 10 años.

BACKGROUND: Medullary thyroid cancer (MTC) represents approximately 5% of all thyroid cancers. Surgery is the only curative treatment, which includes total thyroidectomy and in most cases, neck dissection. AIM: To report our 10-year experience with surgical treatment of MTC. MATERIAL AND METHODS: Review of medical records and pathology reports of a university hospital. We retrieved data from 28 patients aged 47.2 ± 16 years (21 women) operated for a MTC treated between June 2002 and June 2012. RESULTS: In 20 patients, MTC was diagnosed in the preoperative period. Total thyroidectomy was performed in all cases and included a neck dissection in 24 patients. Median follow-up was 48 (2-120) months. Twenty-five patients (89.2%) achieved complete remission of the disease and three had disease recurrence. There were no deaths during the follow up. CONCLUSIONS: The diagnosis of MTC is mainly based on cytology. Total thyroidectomy with neck dissection is the treatment of choice. An early-stage diagnosis is associated with low rates of recurrence and absence of mortality.

[Characteristics and results of breast cancer in elderly females treated with curative intent]. / Cáncer de mama en mujeres adultas mayores, características clínicas e histopatológicas y resultados del tratamiento con intención curativa.

BACKGROUND: Aging is the main risk factor to acquire breast cancer (BC). Nevertheless BC in elderly patients is sub-represented in clinical trials. AIM: To describe the clinical characteristics and long term treatment results of localized BC in older women. MATERIAL AND METHODS: Review of medical records of 65 women aged 70 to 88 years, with localized BC, treated with surgery, postoperative radiotherapy or systemic therapy at a Clinical Hospital in Chile. RESULTS: The presence of symptoms or abnormal findings on physical examination were the main reasons for consulting in 65% of cases. Compared with tumors detected on physical examination, those detected using screening mammogram were smaller and were in stage 1 with a higher frequency (18 and 59% respectively, p < 0.01). The pathological type was luminal in 80% of cases. Overall survival was better for luminal pathological type. All patients completed radiotherapy without interruptions developing minor acute toxicity. The most common co-morbidity was high blood pressure occurring in 46% of patients. Thirteen percent of patients had three or more co-morbidities. After a median follow up of 7 years, 23 (35%) patients had died and the cause of death was BC in 43% of cases. Two patients died of lung cancer. No patient had a local breast relapse. CONCLUSIONS: Screening mammogram in older women detected smaller tumors and it was associated with a better survival. BC is the ultimate cause of death in approximately half of cases.

Carcinoma in situ dentro de un fibroadenoma de mama: tres casos clínicos / Carcinoma within a fibroadenoma of the breast: report of three cases

El fibroadenoma (FA) es un tumor frecuente de la mama que se presenta usualmente en la segunda y tercera década de la vida. Los carcinomas de la mama raramente se desarrollan dentro de un FA, existiendo alrededor de 200 casos descritos en la literatura. Nosotros reportamos la presencia de carcinoma ductal in s/fu(CDIS) al interior de un FA en tres pacientes mujeres de 31, 45 y 47 años. La presencia de microcalcificaciones en dos pacientes y la sospecha de un papiloma intraductal en la tercera, determinaron la necesidad de mastectomía parcial y el consiguiente hallazgo de CDIS al interior de un FA. En dos casos hubo presencia de CDIS extenso en el parénquima mamario adyacente y fueron sometidas finalmente a una mastectomía total. Recomendamos un seguimiento estricto en mujeres con FA a partir de la cuarta década de la vida. En pacientes con lesiones mamarias pro I iterativas o con CDIS que presentan además un FA, se recomienda vigilancia del FA o resección de éste al momento de extirpar el CDIS.

The fibroadenoma (FA) is a common tumor of the breast that usually occurs in the second or third decade of Ufe. The carcinomas of the breast rarely arising within a FA, with around 200 cases reported in the literature. We report the presence of DCIS within a FA on three female patients of 31, 45 and 47 years old. Due to the presence of microcalcifications in two patients and the suspicion of an intraductal papilloma in the third, they underwent a partial mastectomy with the consequent finding of DCIS inside a FA. In two cases there were extensive DCIS in the adjacent breast parenchyma and finally they underwent a total mastectomy. We recommend a strict follow up in women with FA from the fourth decade of life. In patients with proliferatives breast lesions or DCIS that simultaneously presenting a FA, we recommend surveillance of FA or remove it at the same time of the resection of DCIS.