Patrón de recurrencia local en el carcinoma ductal in situ de mama según su inmunofenotipo / Pattern of local recurrence in ductal carcinoma in situ according to the inmunophenotype

Introducción En el carcinoma intraductal o carcinoma ductal in situ (cdis), la sobreexpresión del her2 neu (her2 neu+), alcanza un 60 a 70% de los casos y se asocia con la presencia de alto grado nuclear, comedo-necrosis y baja expresión de receptores hormonales. La asociación entre la sobreexpresión de her2 neu, receptor de estrógeno negativo (re) y alta expresión de factor de proliferación Ki67 (>14%) en pacientes con cdis tendría mayor riesgo de recurrencia local. Objetivos Determinar la frecuencia de sobreexpresión del factor de membrana epidérmico her2 neu en los carcinomas ductales in situ de mama y su relación con la recurrencia local de la enfermedad. Asimismo, determinar la relación entre la sobreexpresión del her2 neu y la supervivencia libre de enfermedad (sle), la supervivencia global (sg), los receptores hormonales y Ki67, y el tipo de recurrencia. Material y método Estudio retrospectivo que incluye pacientes con diagnóstico de cdis de mama en el Servicio de Mastología del Hospital Británico de Buenos Aires operadas entre enero de 2006 y diciembre de 2014. Las variables analizadas fueron la edad, el estado menopáusico, la forma de presentación, el tratamiento quirúrgico y adyuvante, el diagnóstico anátomo-patológico y la inmunohistoquímica, la supervivencia libre de enfermedad y la supervivencia global. Resultados Se incluyeron en el estudio 252 pacientes que cumplían con los criterios de inclusión, agrupándolas según la sobreexpresión o no del receptor de membrana her2 neu en el resultado anátomo-patológico de la pieza operatoria. Sobreexpresaron el receptor de membrana her2 neu (her2 neu+) 86 pacientes (34,1%), mientras que 166 pacientes (65,9%) fueron her2 neu negativo (her2 neu­). Se observó menor número de re negativo en el grupo her2 neu­ (8,4%) vs las pacientes del grupo her2 neu+ (39,5%) (p<0,001). Se registraron 24 recurrencias locales (9,52%), 8 de ellas del grupo her2 neu­ (4,8%) y las 16 restantes del grupo her2 neu+ (18,6%). Se halló una asociación estadísticamente significativa entre la recurrencia local y la sobreexpresión de her2 neu: p=0,04. Conclusiones Se encontró que la sobreexpresión del her2 neu se asoció a una mayor tasa de recurrencia local del carcinoma ductal in situ, con una menor sle en este grupo. También hubo un mayor número de tumores con receptores hormonales negativos en el grupo her2 neu+. En cuanto a la sg, no encontramos diferencias entre ambos grupos

Introduction The incidence of human epidermal growth factor 2 (her2 neu) overexpression or amplification in ductal carcinoma in situ (dcis) is between 60 to 70%, and is associated with the presence of high nuclear grade, comedonecrosis, and low expression of hormonal receptors. There is a higher risk of local recurrence in patients with dcis that overexpress her2 neu, have negative estrogen receptor and high Ki67 (>14%). Objectives Identify patients diagnosed with dcis that overexpressed her2 neu, and its association with local recurrence. Likewise, determine the relationship between her2 neu amplification and disease free survival (dfs), overall survival (os), and expression of hormonal receptors, Ki67 and the type of recurrence. Materials and method Retrospective study, that included patients with dcis diagnosed and surgically treated in the Breast Service of Hospital Britanico de Buenos Aires between January 2006 and December 2014. Demographic information analyzed included age, menopausal status, type of presentation, surgery and adjuvant therapy, histopathological analysis and immunohistochemistry (ihc), dfs and os. Results 252 patients were included and divided in two groups according to the her2 neu expression in the histopathologic result after surgery. The overexpression of her2 neu (her2 neu positive/her2 neu+) was found in 86 patients (34.1%) and 166 patients (65,9%) were her2 neu negative (her2 neu­). In the her2 neu­ group we found less negative estrogen receptor (8.4%) than in the her2 neu+ group (39.5%) (p<0.001). There were 24 local recurrence (9.52%): 8 were her2 neu­ (4.8%) and 16 were her2 neu+ (18.6%). The association between local recurrence and her2 neu overexpression was statistically significant in our analysis: p=0.04. Conclusions The her2 neu overexpression was related with a higher recurrence rate, less dfs. There was also a higher number of tumors with negative estrogen receptor that overexpressed her2 neu. No difference was found in the os between groups

Clinical progress and future of targeted therapy for breast cancer / 中国肿瘤临床

Targeted therapy is one of the most important treatments for breast cancer. In recent years, an increasing number of target-ed therapeutic drugs have been developed for different subtypes of breast cancer. The clinical application of these drugs has greatly improved the efficacy and changed the clinical practice for breast cancer. Overcoming drug resistance and developing new drugs that can go beyond the efficacy of traditional targeted drugs are two of the most important research directions in the future.

Recurrencia y supervivencia en cáncer mamario temprano con inmunofenotipo triple-negativo / Recurrence and survival rates among early breast cancer cases with triple negative immunophenotype

Antecedentes: El estado ganglionar axilar, la expresión de los receptores hormonales y del HER2 son importantes factores pronóstico en cáncer de mama temprano. El inmunofenotipo triple negativo (HER2 y receptores hormonales negativos) se ha asociado con mayor frecuencia de recurrencia y menor tiempo de supervivencia. El objetivo de esta investigación fue evaluar el comportamiento clínico, recurrencia y supervivencia en mujeres con cáncer de mama temprano-triple negativo y otros inmunofenotipos. Material y métodos: Estudio retrospectivo de mujeres en etapas IIIB, mayores de 18 años, en quienes se determinó la expresión de la proteína HER2, receptores de estrógeno y de progesterona a través de inmunohistoquímica. Se identificaron cinco grupos: triple negativo, triple positivo, HER2 negativo y receptores hormonales positivos, HER2 positivo y receptores hormonales negativos, HER2 negativo y un receptor hormonal positivo. En cada caso se analizó la edad, fecha del diagnóstico, etapa clínica, tamaño tumoral, estado ganglionar axilar, receptores de estrógenos, progesterona, HER2, p53, angiogénesis, Ki67, tipo de cirugía realizada, tratamiento adyuvante, tiempo a la recurrencia, número y sitios de la recurrencia, así como el tiempo de sobrevida global. Resultados: 17 pacientes (15.4%) manifestaron el fenotipo triple negativo; 14 (12.7%), triple positivo; 52 (47.3%) en el grupo 3, 11 (10%) en el 4 y 16 (14.5%) en el grupo 5. El fenotipo triple negativo se asoció con proliferación celular aumentada (p<0.000), menor edad (mediana 43 años), mayor tamaño tumoral (mediana 2.5 cm) y menor proporción de pacientes en etapa I, así como mayor frecuencia de expresión positiva de la proteína p53 (78.5%). Observamos mayor frecuencia de recurrencia y de muerte en el grupo triple negativo y en HER2 positivo con receptores hormonales negativos. Conclusiones: El cáncer de mama triple negativo se presenta en mujeres jóvenes y se asocia con proliferación celular aumentada, induce mayor incidencia de recurrencia y de mortalidad. El comportamiento biológico del cáncer de mama con fenotipo triple negativo es agresivo y similar al observado en pacientes con HER2 positivo y receptores hormonales negativos.

BACKGROUND: Axillary lymph node status, hormonal receptors (HR) and HER2 expression are significant prognostic factors for early breast cancer. Triple negative immunophenotype (HER2 and HR negative) is associated with a high frequency of recurrence and lower overall survival. The objective was assess clinical behavior, recurrence and survival of patients with triple negative early breast cancer and patients with other immunophenotypes. MATERIAL AND METHODS: We carried out a retrospective study among women with stages I-IIB over 18 years with determination of HR and HER2 expression by immunohistochemical assay. We identified 5 groups: triple negative, triple positive, HER2 negative & HR positive, HER2 positive & HR negative, HER2 negative & 1 HR positive. We recorded age, date of diagnosis, clinical stage, tumor size, axillary lymph node status, ER, PR, HER2, p53, angiogenesis, Ki67, type of surgery, adjuvant treatment, time to recurrence, number and recurrence site and overall survival. RESULTS: 17 patients (15.4%) had triple negative phenotype, 14 (12.7%) triple positive, 52 (47.3%) were localized in group 3, 11 (10%) in 4 and 16 (14.5%) in group 5. Triple negative phenotype was associated with increased cellular proliferation (p < 0.000); being young (median 43 years), large tumor size (median size 2.5 cm) lower proportion of patients in stage I and high frequency of p53 positive (78.5%). We observed a high frequency of recurrence and death among the triple negative group and among the HER2 positive and HR negative cases. CONCLUSIONS: Triple negative breast cancer is more common among young women and is associated with a high frequency of recurrence and mortality. Clinical behavior among triple negative breast cancer cases is aggressive and displays a similar clinical profile that observed among HER2 positive and HR negative patients.

Characteristics of Late Recurrent Breast Cancers More than 5 Years after Primary Treatment

PURPOSE: The conventional prognostic factors for breast cancer reflect the early short-term prognosis. However, many of these factors cannot predict the long-term prognosis accurately. Therefore, this study evaluated the characteristics of breast cancer that would indicate the development of delayed recurrences after primary treatment. METHODS: Eight hundred and forty nine female breast cancer patients were divided into two groups, an early recurrent (within 5 years) and a late recurrent group (after 5 years). Each conventional prognostic factor including the histological grade (HG), nuclear grade (NG), lympho-vascular invasion (LVI), status of hormonal receptor, p53 and c-erbB2 were compared to identify any factor that would show significant difference. RESULTS: The overall recurrence rate was 14.2% (121/849), which was significantly higher in patients with a high TNM stage, high HG and NG, positive LVI, negative receptor status and expression of p53 (P0.05). However, the positive rate of the hormonal receptor was significantly higher in the late recurrent group (P=0.019). All these factors, except for c-erbB2 over-expression, were independent prognostic factors for a recurrence within 5 years (P0.05). CONCLUSION: The positive hormone receptor of breast cancer is a good early prognostic factor that can also predict late recurrences.