Research progress on targeted therapy of breast cancer with low expression of HER2 / 国际肿瘤学杂志

Breast cancer has become the malignant tumor with the highest incidence rate among women, of which human epidermal growth factor receptor 2 (HER2) positive breast cancer accounts for about 15%-20%. With the development of anti HER2 targeted drugs, the survival and prognosis of HER2 positive breast cancer has significantly benefited. About 45%-55% of breast cancer patients have low HER2 expression, and these patients usually do not receive anti HER2 treatment. However, there is a significant difference between the biological behavior and prognosis of breast cancer with low HER2 expression and breast cancer with zero HER2 expression. It is helpful to differentiate and adopt corresponding treatment strategies to improve the prognosis of patients. At present, there have been many advances in targeted therapy of breast cancer with low HER2 expression, which provides a useful reference for precision treatment of breast cancer with low HER2 expression.

Análisis de la coexpresión de HER2/GRB7 y su asociación con variables clinicopatológicas en un grupo de mujeres colombianas con diagnóstico de cáncer de mama invasivo / Analysis of HER2/GRB7 co-expression and its association with clinicopathological variables in a group of Colombian women diagnosed with invasive breast cancer

Objetivo. Analizar las diferencias en la presentación de variables clínico-patológicas, de acuerdo con la expresión proteica de GRB7, en tumores HER2 positivos en mujeres colombianas con cáncer de mama invasivo, diagnosticado entre los años 2013 y 2015 en el Instituto Nacional de Cancerología E.S.E (INC). Métodos. Se incluyeron 158 pacientes con diagnóstico confirmado de cáncer de mama ductal invasivo. Se evaluó la expresión de los receptores hormonales (receptor de estrógeno (RE) y de progesterona (RP)), HER2, Ki67 y GRB7, mediante inmunohistoquímica (IHQ), y a partir de estos, se clasificaron los tumores en subtipos intrínsecos. Los análisis estadísticos incluyeron las pruebas de Chi-cuadrado/test exacto de Fisher para las variables categóricas, y la prueba U Mann Whitney/ Kruskal Wallis para las variables cuantitativas. Se evaluó la supervivencia global (SG) y libre de enfermedad (SLR) según la coexpresión de HER2/GRB7 usando el método de Kaplan-Meier y el test de log-rank. Resultados. La expresión de GRB7 se observó exclusivamente en tumores HER2-positivos (luminal B/HER2+ y HER2-enriquecidos: p<0,001). Los casos HER2+/GRB7+ mostraron una mayor expresión de Ki67 (40% vs. 27,5%, p=0,029), pero una tendencia a presentar un menor tamaño tumoral (30 mm vs. 51 mm, p=0,097), comparado con los tumores HER2+/GRB7-. No obstante, no se observaron diferencias en la supervivencia según la coexpresión de HER2/GRB7 (SG: p=0,6; SLR: p=0,07). Conclusiones. En nuestra muestra de estudio, la expresión de GRB7 en tumores HER2+ no se asoció con características clínico-patológicas de pronóstico desfavorable.

Objective: To analyze differences in the presentation of clinicopathological variables according to GRB7 protein expression in HER2-positive tumors in Colombian patients with invasive ductal breast carcinomas diagnosed between 2013 and 2015 at the Instituto Nacional de Cancerología (Bogotá, Colombia).Methods: A total of 158 breast cancer patients were included with a confirmed diagnosis of invasive ductal carcinoma. A single pathologist evaluated the protein expression of hormone receptors (estrogen (ER) and progesterone receptor (PR)), HER2, Ki67, and GRB7 by immunohistochemistry (IHC). The chi-square and Fisher's exact tests were used to assess differences between categorical variables, as well as the Mann-Whitney/Kruskal-Wallis U test for numerical variables. Overall (OS) and disease-free (DFS) survival were evaluated according to HER2/GRB7 co-expression using the Kaplan-Meier method and log-rank test.Results:GRB7 expression was observed exclusively in HER2-positive tumors (luminal B/HER2+ and HER2-enriched: p<0.001). HER2+/GRB7+ cases showed higher Ki67 expression (40% vs. 27.5%, p=0.029) and a tendency to present a smaller tumor (30 mm vs. 51 mm, p=0.097) compared to HER2+/GRB7- tumors. However, no differences in OS or DFS were observed by HER2/GRB7 co-expression (OS: p=0.6; DFS: p=0.07).Conclusions:Our results in Colombian patients indicate that GRB7 expression in HER2-positive breast tumors is not associated with unfavorable clinicopathological features.

Tratamiento sistémico para el cáncer de mama HER2 positivo avanzado. Revisión de la evidencia y abordaje terapéutico en el Instituto Nacional de Cancerología - Colombia / Systemic treatment for advanced HER2 positive breast cancer. Review of the evidence and therapeutic approach at the Instituto Nacional de Cancerología - Colombia

El cáncer de mama es la neoplasia más frecuente y de mayor mortalidad en las mujeres en todo el mundo. El receptor 2 del factor de crecimiento epidérmico humano (HER2) se sobreexpresa en aproximadamente el 20% de las pacientes con cáncer de mama y se asocia a mayor riesgo de recidiva tumoral y mortalidad. Antes del desarrollo de los anticuerpos monoclonales dirigidos contra HER2, el cáncer de mama HER2 positivo estaba asociado con un pronóstico desfavorable. El uso de las terapias dirigidas anti HER2 ha mejorado significativamente las tasas de supervivencia global tanto en el escenario adyuvante como en la enfermedad metastásica. En los últimos años han surgido nuevos medicamentos que bloquean esta vía de señalización, lo cual ha permitido establecer varias líneas de tratamiento con terapia anti HER2 en las pacientes con enfermedad metastásica. Por esta razón, las unidades funcionales de Oncología Clínica/Seno y Tejidos Blandos tomaron la decisión de realizar una revisión de la evidencia científica disponible a octubre de 2021, para establecer las recomendaciones en el abordaje terapéutico de las pacientes con cáncer de mama metastásico HER2 positivo en el Instituto Nacional de Cancerología (INC).

Breast cancer is the most common neoplasm and the one with the highest mortality in women worldwide. Human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 20% of breast cancer patients and is associated with an increased risk of tumor recurrence and mortality. Before the development of monoclonal antibodies directed against HER2, HER2-positive breast cancer was associated with a poor prognosis. The use of anti-HER2 targeted therapies has significantly improved overall survival rates both in the adjuvant setting and in metastatic disease. In recent years, new drugs have emerged that block this signaling pathway, which has made it possible to establish several lines of treatment with anti-HER2 therapy in patients with metastatic disease. For this reason, the clinical oncology/breast and soft tissue functional units made the decision to conduct a review of the available scientific evidence as of October 2021 to establish recommendations for the therapeutic approach to patients with HER2-positive metastatic breast cancer in the National Cancer Institute (INC).

Indicaciones para el uso de pertuzumab en cáncer de mama HER2 positivono metastásico en los escenarios neoadyuvante y adyuvante. Revisión de la evidencia y abordaje terapéutico en el Instituto Nacional de Cancerología - Colombia / Indications for the use of pertuzumab in non-metastatic HER2-positive breast cancer in the neoadjuvant and adjuvant. Review of the literature and therapeutic approach at the Instituto Nacional de Cancerología - Colombia

La adición de la terapia dirigida a la quimioterapia citotóxica en pacientes con cáncer de mama ha mejorado significativamente los desenlaces oncológicos en las pacientes con tumores HER2 positivo. El uso de pertuzumab durante el manejo neoadyuvante incrementa significativamente la respuesta patológica completa y en la actualidad permite emplear regímenes libres de antraciclinas con una eficacia similar y menores efectos cardiovasculares (en especial sobre la fracción de eyección). El beneficio en supervivencia libre de enfermedad invasiva, de adicionar pertuzumab en el escenario adyuvante en las pacientes sin tratamiento anti HER2 previo, está limitado a aquellas con ganglios positivos. La implementación de esquemas con bloqueo dual anti HER2, durante el tratamiento inicial del cáncer de mama HER2 positivo, mejora significativamente el pronóstico oncológico en este grupo de pacientes.

The addition of targeted therapy to cytotoxic chemotherapy in patients with breast cancer has significantly improved oncologic outcomes in patients with HER2-positive tumors. The use of pertuzumab during neoadjuvant management significantly increases the complete pathological response and currently allows the use of anthracycline-free regimens with similar efficacy and fewer cardiovascular effects (especially on ejection fraction). The benefit of pertuzumab in disease-free survival in the adjuvant setting for patients without prior anti-HER2 treatment is limited to those with positive nodes. The implementation of schemes with dual anti-HER2 blockade during the initial treatment of HER2-positive breast cancer significantly improves the oncological outcomes in this group of patients.

Study on the efficacy and influencing factors of pyrotinib in treatment of patients with human epidermal growth factor receptor 2-positive metastatic breast cancer / 肿瘤研究与临床

Objective:To evaluate the efficacy of oral pyrotinib in treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in the real world, and to explore its influencing factors.Methods:The clinical data of 148 patients with HER2-positive metastatic breast cancer treated with oral pyrrolitinib in Shanxi Cancer Hospital from September 2018 to December 2020 were retrospectively analyzed. The efficacy was evaluated according to the efficacy evaluation criteria for solid tumors, version 1.1, and the adverse effects were graded according to the National Cancer Institute common terminology criteria of adverse effects, version 4.0. The Kaplan-Meier method was used to draw progression-free survival (PFS) curves, the patients were stratified by different clinical characteristics, and log-rank test was used for univariate analysis of PFS; the multivariate analysis of PFS was performed using Cox proportional hazards model.Results:The objective response rate (ORR) of 148 patients was 71.6% (106/148), and the disease control rate (DCR) was 89.2% (132/148). The overall median PFS time was 11.0 months (95% CI 10.1-11.9 months), and the median PFS of 19 patients with brain metastases was 10.0 months (95% CI 7.4-12.6 months). The differences in PFS between patients stratified by disease-free interval (DFI), the number of metastatic site and Eastern Cooperative Oncology Group (ECOG) score were statistically significant (all P < 0.05), but the difference in PFS between patients with negative and positive hormone receptor was not statistically significant ( P > 0.05). Multivariate Cox regression analysis showed that DFI (>1 year vs. ≤1 year: HR = 5.254, 95% CI 0.728-37.933, P = 0.046) and ECOG score (≥2 points vs. 0-1 point: HR = 2.454, 95% CI 1.261-4.788, P = 0.008) were independent influencing factors of PFS. The most common ≥grade 3 adverse effects were diarrhea (31 cases, 20.9%) and hand-foot syndrome (38 cases, 25.8%). Conclusions:The pyrotinib has definite efficacy and good safety in the treatment of HER2-positive metastatic breast cancer in the real world, especially for patients with DFI > 1 year and ECOG score 0-1 point, the efficacy and safety are particularly good.

Progress of human epidermal growth factor receptor 2 expression in breast cancer and its detection methods / 肿瘤研究与临床

Positively expressed human epidermal growth factor receptor 2 (HER2) occurs in 20%-30% of breast cancer patients, and the prognosis of them is generally poor. Fortunately, the application of HER2-targeted drugs has bright hopes for these patients. The comprehensive detection strategy of immunohistochemistry (IHC) for detecting HER2 protein overexpression combined with fluorescence in situ hybridization (FISH) for detecting HER2 gene amplification is widely used in HER2 breast cancer. However, this strategy applied in some patients with specially expressed HER2 in clinic is still controversial. RNAscope technique can make in situ analysis of HER2 mRNA expression and can be used as a complementary method. This paper summarizes the detection methods of HER2 on protein, DNA and RNA levels in order to provide references for accurate HER2 detection methods in breast cancer.

Cardiotoxicity of anti-human epidermal growth factor receptor 2 monoclonal antibody in breast cancer treatment / 肿瘤研究与临床

Targeted therapy characterized with high specificity and low toxicity, is an important treatment method for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which can prolong the disease-free survival and the overall survival time of HER2-positive early breast cancer patients, and prolong the progression-free survival and the overall survival time of HER2-positive advanced patients with breast cancer. However, targeted drugs blocked the normal signaling pathway outside the target organs, and some patients experienced treatment-related adverse reactions, resulting in dose reduction, treatment delay and interruption, or even life-threatening consequences. Cardiotoxicity is one of the potentially serious side effects of targeted-HER2 drugs. Currently the targeted drugs for treatment of HER2-positive breast cancer patients include macromolecular monoclonal antibody drugs such as trastuzumab and pertuzumab, antibody-drug conjugates such as T-DM1 and T-DXd, and small-molecule tyrosine kinase inhibitors. This paper reviews the cardiotoxicity of HER2 targeted drugs including antibody-drug conjugates monoclonal antibody drugs in targeted therapy for breast cancer in order to provide references for clinical treatment.

Research progress in HER2-low breast cancer / 中国医师杂志

The latest statistics show that breast cancer (BC) has become the cancer with the highest incidence in the world, seriously affecting women′s physical and mental health, and has become a hot research topic in the medical field. Accordingly, its treatment has also entered the molecular era. According to its molecular classification, BC is mainly divided into Luminal A, Luminal B, simple human epidermal growth factor receptor 2 (HER2)-positive and triple negetive breast cancer (TNBC). Obviously, correct judgment of HER2 expression status is very important for cancer typing and treatment of breast cancer. With the further development of research, some scholars have recently put forward new viewpoints and views on the interpretation of HER2 expression and cancer typing in breast cancer. This review will introduce the HER2-low breast cancer combined with the current frontier viewpoint and research findings, hoping to provide a reference for the precision treatment of breast cancer in the later stage and related further research.

Tratamiento Neoadyuvante en cáncer de mama HER2 positivo. La era de la terapia dirigida / Neoadjuvant treatment in HER2 positive breast cancer. The Age of Targeted Therapy

Introducción: El tratamiento neodyuvante del cáncer de mama HER2 positivo ha ido evolucionando a través del tiempo, con la implementación de nuevas estrategias de manejo terapéutico. Es de esta manera como el trastuzumab, un anticuerpo monoclonal anti-HER2sigue siendo el tratamiento estándar en este subtipo de cáncer, los primeros estudios en los que se evidencia su eficacia son el realizado por el Dr. Buzdar y el estudio NOAH en los cuales las pacientes alcanzaron mayores tasas de respuesta patológica completa en comparación con quimioterapia sola, así como también un mayor número de cirugías conservadoras de mama en lugar de mastectomía.Con el paso de los años se han ido desarrollando nuevas estrategias de manejo terapéutico, así tenemos el doble bloqueo anti-HER2 con los anticuerpos monoclonales trastuzumab y pertuzumab que han mejorado las tasas de respuesta patológica completa. Además se ha incluido al lapatinib un inhibidor de tirosina quinasa como parte de las terapias dirigidas. Se ha dilucidado si las antraciclinas confieren un beneficio adicional al tratamiento neoadyuvante y los estudios demuestran que el beneficio es el mismo queotros esquemas de quimioterapia. Es en realidad la quimioterapia indispensable en la neoadyuvancia, el estudio PHERGain demuestra que existen pacientes que pueden alcanzar respuesta patológica completa solo con el doble bloqueo anti-her2 (trastuzumab y pertuzumab) lo que evitaría la toxicidad innecesaria por quimioterapia, y se podrían desarrollar estrategias para el manejo de aquellas pacientes que no alcanzaron una respuestapatológica completa posterior al doble bloqueo. Aún queda un campo amplio por explorar y con estudios en curso al momento. Palabras claves:DsCS:Receptor ErbB-2, Trastuzumab, Neoplasias de la Mama, Quimioterapia Adyuvante, Ado-Trastuzumab Emtansina

Introduction:The neodyuvanttreatment of HER2 positive breast cancer has evolved over time, with the implementation of new therapeutic management strategies. It is in this way that trastuzumab, an anti-HER2 monoclonal antibody continues to be the standard treatment in this subtype of cancer, the first studies in which its efficacy is evidenced are the one carried out by Dr. Buzdar and the NOAH study in which patients achieved higher rates of complete pathological response compared to chemotherapy alone, as well as a higher number of breast-conserving surgeries rather than mastectomy.Over the years, new therapeutic management strategies have been developed, thus we have the double anti-HER2 blockade with the monoclonal antibodies trastuzumab and pertuzumab that have improved the ratesof complete pathological response. In addition, lapatinib, a tyrosine kinase inhibitor, has been included as part of targeted therapies. It has been elucidated whether anthracyclines confer an additional benefit to neoadjuvant treatment and studies show that the benefit is the same as other chemotherapy regimens.It is actually the essential chemotherapy in neoadjuvant therapy, the PHERGain study shows that there are patients who can achieve a complete pathological response only with the double anti-her2 blockade (trastuzumab and pertuzumab), which would avoid unnecessary toxicity due to chemotherapy, and strategies could be developed for the management of those patients who did not achieve a complete pathological response after double blockade. There is still a wide field to explore and with studies underway at the moment. Keywords:MESH:Receptor, ErbB-2;Trastuzumab; Breast Neoplasms; Chemotherapy, Adjuvant; Ado-Trastuzumab Emtansine

Diagnóstico y tratamiento del cáncer de mama HER2+: Guía de Práctica Clínica de la Sociedad Peruana de Cancerología / Diagnosis and treatment of HER2 + breast cancer: Clinical Practice Guide of the Peruvian Society of Cancerology

RESUMEN Introducción. En Perú, el cáncer de mama representa el tipo de cáncer más frecuente en mujeres y el sexto tipo de cáncer más letal en la población general. La sobreexpresión del receptor del factor de crecimiento epidérmico (HER2+) ocurre en 20% a 30% de los cánceres de mama, y se asocia con tumores más agresivos, con mayor recurrencia y mayor mortalidad. Objetivo. Elaborar un conjunto de recomendaciones basadas en evidencias para el diagnóstico y tratamiento del cáncer de mama HER2+, con la finalidad de contribuir a reducir la mortalidad, progresión de la enfermedad y mejorar la calidad de vida. Métodos. Se conformó un panel de especialistas clínicos y metodólogos, quienes identificaron preguntas clínicas relevantes sobre el diagnóstico y tratamiento del cáncer de mama HER2+. Se desarrolló una búsqueda sistemática de GPC en Medline (PubMed), y en organismos elaboradores y recopiladores. Para la formulación de recomendaciones, el panel de especialistas discutió la evidencia y elementos del contexto de implementación de la recomendación, siguiendo la metodología propuesta por el Ministerio de Salud del Perú. Resultados. Se priorizó nueve preguntas clínicas. Se formuló un total de 25 recomendaciones clínicas. Conclusiones. Se elaboró una GPC basada en evidencias, a través de un proceso sistemático, riguroso y transparente desarrollado por un equipo multidisciplinario.

ABSTRACT Introduction. In Peru, breast cancer represents the most common type of cancer in women and the sixth most lethal type of cancer in the general population. Overexpression of the epidermal growth factor receptor (HER2 +) occurs in 20% to 30% of breast cancers, and is associated with more aggressive tumors, with greater recurrence and greater mortality. Objective. Prepare a set of evidence-based recommendations for the diagnosis and treatment of HER2 + breast cancer, in order to help reduce mortality, disease progression and improve quality of life. Methods. A panel of clinical specialists and methodologists was formed, who identified relevant clinical questions about the diagnosis and treatment of HER2 + breast cancer. A systematic search for CPGs was carried out in Medline (PubMed), and in developing and compiling agencies. For the formulation of recommendations, the panel of specialists discussed the evidence and elements of the context of implementation of the recommendation, following the methodology proposed by the Ministry of Health of Peru. Results. Nine clinical questions were prioritized. A total of 25 clinical recommendations were made. Conclusions. An evidence-based CPG was developed through a systematic, rigorous and transparent process developed by a multidisciplinary team.

Tratamiento del Cáncer de Mama Metastásico, Receptor Hormonal Positivo, Her 2 Negativo: Enfoque actual a Dianas Terapéuticas / Treatment of Metastatic Breast Cancer, Hormone Receptor Positive, Her 2 Negative: Current Approach to Therapeutic Targets

En el cáncer de mama luminal, la terapia hormonal está indicada en adyuvancia y neoadyuvancia. El estadio metastásico incluye un grupo heterogéneo de tumores que varían de acuerdo con el sitio de metástasis, tiempo de aparición, condición general de las pacientes, entre otras características intrínsecas del tumor. Esto establece tiempos de sobrevida con rangos variables de meses a muchos años. Los estrógenos actúan en receptores de membrana citoplasmática y nuclear: en las células neoplásicas estimulan la transcripción del ARN, con persistencia de la proliferación. El bloqueo de la acción hormonal en el cáncer avanzado encuentra mecanismos de resistencia con el uso de vías de señalización paralelas, este conocimiento ha permitido el desarrollo de inhibidores de CDK 4/6, mTOR y PIK3-CA, que se recomiendan en enfermedad metastásica, con prolongación significativa de la supervivencia global. En crisis visceral aún se mantiene el uso de quimioterapia sistémica secuencial o combinada

For a patient with estrogen receptor positivebreast cancer, the adjuvant and neoadjuvant endocrine therapy has an absolute benefit. The metastatic stage includes a diverse group of tumors that vary according to the site of metastasis, time of appear, general condition of the patients, and other intrinsic characteristics of the tumor. survival in cancer varies according these features, from a few months to many years. Estrogen hormones stimulate nuclear and cytoplasmic receptors. In neoplastic cells, estrogen regulate RNA transcription, with persistence of proliferation. The blocking of hormonal action in metastatic cancer, has resistance mechanisms with the use of parallel signaling pathways, this knowledge has allowed the development of inhibitors of CDK 4/6, mTOR and PIK3-CA, which are recommended in metastatic disease. with significant prolongation of overall survival. In visceral crisis, the use of sequential or combined systemic chemotherapy is still maintained

Accuracy of breast magnetic resonance imaging in evaluating the response to neoadjuvant chemotherapy: a study of 310 cases at a cancer center / Acurácia da ressonância magnética das mamas na avaliação da resposta a quimioterapia neoadjuvante: estudo de 310 casos em um centro oncológico

Abstract Objective: To evaluate the accuracy of magnetic resonance imaging (MRI) of the breasts in the identification of a pathological complete response in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC). Materials and Methods: This was a single-center, retrospective, observational study designed to validate a diagnostic test. The following variables were evaluated: age; results of the histological and immunohistochemical analysis of the biopsy; post-NAC MRI findings; and results of the histological analysis of the surgical specimen, using the residual cancer burden index. The radiological response, as assessed by MRI, was compared with the pathological response, as assessed by histological analysis of the surgical specimen (the gold standard method). Results: We evaluated 310 tumors in 308 patients. The mean age of the patients was 47 years (range, 27-85 years). For identifying a pathological complete response, breast MRI had an overall accuracy of 79%, with a sensitivity of 75%, specificity of 83%, positive predictive value of 75%, and negative predictive value of 83%. When that accuracy was stratified by molecular subtype, it was best for the HER2 subtype, with a sensitivity and specificity of 82% and 89%, respectively, followed by the triple-negative subtype, with a sensitivity and specificity of 78% and 83%, respectively. Conclusion: Breast MRI showed good accuracy in the prediction of a pathological complete response after NAC. The sensitivity and positive predictive value were highest for the HER2 and triple-negative subtypes.

Resumo Objetivo: Avaliar a acurácia da ressonância magnética (RM) das mamas na identificação de resposta patológica completa em pacientes com câncer de mama submetidas a quimioterapia neoadjuvante (QTN). Materiais e Métodos: Teste de validação diagnóstica, realizado por meio de estudo observacional, unicêntrico e retrospectivo. As variáveis avaliadas no estudo foram idade, resultado histológico e imuno-histoquímico da biópsia, análise da RM após QTN e análise histológica da peça cirúrgica, com cálculo do índice residual cancer burden. Os resultados da resposta radiológica pela RM foram comparados com a resposta patológica na peça cirúrgica (padrão ouro). Resultados: Foram incluídos 310 tumores de 308 pacientes com média de idade de 47 anos (variação: 27 a 85 anos). A acurácia da RM foi 79%, com sensibilidade de 75%, especificidade de 83%, valor preditivo positivo de 75% e valor preditivo negativo de 83%. Estratificando-se por subtipo molecular, a detecção da resposta patológica pela RM obteve os melhores porcentuais de acerto no subtipo HER2 superexpresso, com sensibilidade e especificidade de 82% e 89%, respectivamente, seguido do subtipo triplo negativo, com sensibilidade e especificidade de 78% e 83%, respectivamente. Conclusão: A RM demonstrou boa acurácia na predição de resposta patológica completa após QTN. A sensibilidade e o valor preditivo positivo foram mais altos nos subtipos triplo negativo e HER2 superexpresso.

Parámetros de la 18F-FDG PET/CT asociado con los factores pronósticos en la estadificación inicial del Cáncer de Mama / Parameters of the 18F-FDG PET/CT associated with the prognostic factors in the initial staging of Breast Cancer

Propósito de la revisión: Este artículo tiene la siguiente pregunta de investigación: ¿Se debe considerar la Biología, histología y el fenotipo para la estadificación inicial del Cáncer de Mama? Se realiza una revisión del estudio metabólico del cáncer de mama (CM) con la técnica de la captación de glucosa Fluorada 18-Fluoro-2-Desoxi-D-Glucosa y su medición de intensidad con tomografía por Emisión de positrones (18F-FDG PET/CT). Recientes Hallazgos: La 18F-FDG PET/CT puede detectar metástasis que no son visibles en otras modalidades, el carcinoma ductal invasivo muestra una mayor captación que el carcinoma lobular invasivo. La alta captación de 18F-FDG se ha asociado con un resultado peor y una supervivencia más corta. Extracto: El cáncer de mama es un tipo heterogéneo de malignidad porque varios factores afectan su comportamiento y pronóstico. Debido a esta heterogeneidad, el tratamiento óptimo y la respuesta esperada al tratamiento puede variar sustancialmente para cada paciente. 18F-FDG PET/CT puede proporcionar información relevante sobre el metabolismo, el diagnóstico y el pronóstico del cáncer de mama. Varios estudios han sugerido una correlación entre las características clínico-patológicas del cáncer de mama y los parámetros metabólicos obtenidos por 18F-FDG PET/CT.

Purpose of the review: This article has the following research question: Should biology, histology and phenotype be considered for initial staging of breast cancer? A review of the metabolic study of breast cancer (CM) is performed with the technique of glucose uptake Fluorada 18-Fluoro-2-Deoxy-D-Glucose and its intensity measurement with positron emission tomography (18F-FDG PET / CT). Recent Findings: 18F-FDG PET / CT can detect metastases that are not visible in other modalities, invasive ductal carcinoma shows a higher uptake than invasive lobular carcinoma. The high uptake of 18F-FDG has been associated with a worse outcome and shorter survival. Excerpt: Breast cancer is a heterogeneous type of malignancy because several factors affect its behavior and prognosis. Due to this heterogeneity, the optimal treatment and the expected response to treatment may vary substantially for each patient. 18F-FDG PET / CT can provide relevant information on the metabolism, diagnosis and prognosis of breast cancer. Several studies have suggested a correlation between the clinical-pathological characteristics of breast cancer and the metabolic parameters obtained by 18F-FDG PET / CT.

Impact of HER2 receptor status on axillary nodal burden in patients with non-luminal A invasive ductal breast carcinoma / Receptores HER2, compromiso ganglionar axilar y sobrevida en mujeres con cáncer de mama ductal invasivo

ABSTRACT Background: Breast cancer (BC) is the most common malignancy in women. Aim: To assess the impact of HER2 status on axillary lymph node (ALN) involvement in patients with invasive ductal carcinoma of no special type (IDC-NST) both at diagnosis and during the 4-year postoperative period. Patients and Methods: We retrospectively included 375 women with an early clinical stage of non-luminal IDC-NST who between 2007 and 2013 underwent breast surgery at a clinical hospital. They were divided into phenotype-based groups: HR+HER2-, HR+HER2+, HR-HER2+ and HR-HER2-. Only patients with sentinel lymph node (SLN) macrometastases underwent ALN dissection. If > 3 ALNs were positive, radiotherapy was delivered. All patients were treated with chemotherapy, HER2+ BC patients received trastuzumab, and hormone receptor (HR)-positive BC patients received hormonal therapy. Results: Larger tumor size, higher grade, HR+, HER2+ status, and lymphovascular invasion (LVI) were predictive for ALN metastases at diagnosis. The poorest overall, disease-free, and distant recurrence-free survival (OS, DFS, DRFS) were found in the HR-HER2- group, while the poorest locoregional recurrence-free survival (LRFS) was observed in HR-HER2+ and HR-HER2- groups. HER2 status was not predictor of survival. Conclusions: HER2+ status was predictive for ALN involvement at diagnosis but had no effect on 4-year LRFS in these patients.

Antecedentes: El cáncer de mama es el tumor maligno más común en mujeres. Objetivo: Conocer el impacto del estado HER2 sobre el compromiso ganglionar axilar al momento del diagnóstico y durante los primeros cuatro años después de la cirugía en mujeres con carcinoma ductal invasivo de tipo no especial (IDC-NST). Pacientes y Métodos: Incluimos retrospectivamente a 375 mujeres en etapas clínicas iniciales de IDC-NST que fueron operadas en un hospital clínico. Ellas se dividieron en grupos de acuerdo al fenotipo: HR+HER2-, HR+HER2+, HR-HER2+y HR-HER2-. La disección de ganglios axilares se efectuó solo en las pacientes con macrometástasis en el ganglio centinela. Si había más de tres ganglios comprometidos, se efectuó radioterapia. Todas las pacientes se trataron con quimioterapia. Las pacientes HER2+ recibieron trastuzumab y las pacientes HR+ recibieron hormonoterapia. Resultados: Tumores más grandes, de mayor grado de malignidad, HR+, HER2+ y la invasión linfovascular fueron predictivos de la presencia de metástasis axilares al momento del diagnóstico. La sobrevida más baja se observó en pacientes HR-HER2+. La sobrevida libre de recurrencia locorregional más baja, se observó en pacientes HR-HER2+ y HR-HER2-. HER2 no fue predictor de sobrevida. Conclusiones: En estas mujeres, HER2+fue predictor de la presencia de compromiso ganglionar axilar al momento del diagnóstico pero no de la sobrevida a cuatro años.

Measuring Tumor Extent Based on Subtypes Using Magnetic Resonance Imaging: Radiologic-Pathologic Discordance and High Positive Margin Rates in Breast Cancer / 한국유방암학회지

PURPOSE: We evaluated the clinical value of breast magnetic resonance imaging (MRI) in patients who underwent breast-conserving surgery (BCS). The degree of correlation between pathology size and MRI or ultrasonography (US) size was compared based on breast cancer subtypes. In addition, we investigated the positive margin rates. METHODS: Patients with invasive breast cancer who underwent preoperative breast MRI and US between 2011 and 2016 were included in the study. Lin's concordance correlation coefficient was used to measure the correlation between MRI or US andpathologic tumor extent. Tumor extent was defined as pathologic tumor size, including in situ carcinoma. Margin positivity was assessed based on frozen-section examination. RESULTS: A total of 516 patients with a single tumor who underwent BCS were included in the study. The correlation between pathologic size and MRI was significantly higher than that of US (r = 0.6975 vs. 0.6211, p = 0.001). The superiority of MRI over US in measuring the pathologic extent was only observed in triple-negative breast cancer (TNBC; r = 0.8089 vs. 0.6014, p < 0.001). The agreement between MRI or US and tumor extent was low for the human epidermal growth factor receptor 2 (HER2)-positive subtype (MRI: 0.5243, US: 0.4898). Moreover, the positive margin rate was higher in the HER2-positive subtype than in the others (luminal/HER2-negative: 11.6%, HER2-positive: 23.2%, TNBC: 17.8%, p = 0.019). The post hoc analysis showed that the HER2-positive subtype was more likely to show positive margins than the luminal/HER2-negative subtype (p = 0.007). CONCLUSION: Breast MRI was superior to US in the preoperative assessment of the pathologic extent of tumor size; this was most evident in TNBC. For HER2-positive tumors, imaging-pathologic discordance resulted in higher positive margin rates than that with other subtypes.

Human Epidermal Growth Factor Receptor 2-positive Mucinous Carcinoma with Signet Ring Cell Differentiation, Which Showed Complete Response after Neoadjuvant Chemotherapy / 한국유방암학회지

Mucinous carcinoma (MC) is a rare subtype of breast cancer, which is composed of tumor cells floating in the abundant extracellular mucin. This form of cancer is usually estrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 (HER2) negative. Here, we present a case of HER2-positive MC with an unusual signet ring cell differentiation. It is very rare that a breast tumor consists entirely of signet ring cells. The tumor showed pathologic complete response (pCR) after neoadjuvant chemotherapy with trastuzumab and pertuzumab. pCR of HER2-positive MC has rarely been described in literature. It is important to consider the biological heterogeneity of MCs for effective management.

Correlation of quantitative parameters of dynamic enhanced magnetic resonance imaging with Dukes stage, lymph node metastasis and tumor differentiation degree of rectal cancer / 中国医师杂志

Objective@#To explore the correlation between quantitative parameters of dynamic enhanced magnetic resonance imaging (DCE-MRI) and Dukes stage, lymph node metastasis, tumor differentiation degree and molecular biological indicators [Ki67 and human epidermal growth factor receptor 2 (CerbB-2)] of rectal cancer.@*Methods@#This study was a prospective study. From October 2014 to October 2017, 168 cases of rectal cancer patients were selected as the research objects. DCE-MRI was performed preoperatively to obtain the quantitative parameter values of region of interest (ROI) [apparent diffusion coefficient (ADC)mean, Ktrans, Ve, and Kep] in tumor site. The expression of Ki67 and CerbB-2 were detected by immunohistochemical. Correlations of DCE-MRI quantitative parameter values and rectal cancer Dukes staging, lymph node metastasis, tumor differentiation degree to Ki67 and CerbB-2 expression level were analysised.@*Results@#With the increase of tumor differentiation, ADCmean was increasing, while Ktrans and Ve showed a downward trend, with significant difference (P<0.05). Among them, Ktrans and Ve in the high-differentiation group and the medium-differentiation group were significantly lower than those in the low-differentiation group (P<0.05), while there was no statistical significance between the high-differentiation group and the medium-differentiation group (P>0.05). The ADCmean was statistically significant between different groups (P<0.05), while Kep was not statistically significant (P>0.05). The ADCmean of lymph node metastasis group was significantly lower than that of no lymph node metastasis group (P<0.001), while Ktrans, Ve and Kep were significantly higher than that of no lymph node metastasis group (P<0.001). With the increase of Dukes staging in rectal cancer, ADCmean was decreasing and Ktrans was increasing, with statistically significant difference (P<0.001); among which the ADCmean of Dukes A and B was significantly higher than that of Dukes C and D (P<0.05), and Ktrans was significantly lower than that of Dukes C and D (P<0.05). Ktrans and Kep were increased with the increased expression levels of Ki67 and CerbB-2, and the difference between Ktrans and Kep was statistically significant (P<0.05). The ADCmean decreased with the increase of Ki67 and CerbB-2 expression level, and the difference was statistically significant (P<0.05).@*Conclusions@#DCE-MRI quantitatively participates can reflect the biological behavior of rectal cancer, and can be used to evaluate the prognosis of tumors and guide the clinical selection of more appropriate treatment options.

Correlation of quantitative parameters of dynamic enhanced magnetic resonance imaging with Dukes stage, lymph node metastasis and tumor differentiation degree of rectal cancer / 中国医师杂志

Objective To explore the correlation between quantitative parameters of dynamic enhanced magnetic resonance imaging (DCE-MRI) and Dukes stage,lymph node metastasis,tumor differentiation degree and molecular biological indicators [Ki67 and human epidermal growth factor receptor 2 (CerbB-2)] of rectal cancer.Methods This study was a prospective study.From October 2014 to October 2017,168 cases of rectal cancer patients were selected as the research objects.DCE-MRI was performed preoperatively to obtain the quantitative parameter values of region of interest (ROI) [apparent diffusion coefficient (ADC) Ktrans,Ve,and Kep] in tumor site.The expression of Ki67 and CerbB-2 were detected by immunohistochemical.Correlations of DCE-MRI quantitative parameter values and rectal cancer Dukes staging,lymph node metastasis,tumor differentiation degree to Ki67 and CerbB-2 expression level were analysised.Results With the increase of tumor differentiation,ADCmean was increasing,while Ktrans and Ve showed a downward trend,with significant difference (P ＜ 0.05).Among them,Ktrans and Ve in the high-differentiation group and the medium-differentiation group were significantly lower than those in the low-differentiation group (P ＜ 0.05),while there was no statistical significance between the high-differentiation group and the medium-differentiation group (P ＞ 0.05).The ADC was statistically significant between different groups (P ＜ 0.05),while Kep was not statistically significant (P ＞ 0.05).The ADCmean of lymph node metastasis group was significantly lower than that of no lymph node metastasis group (P ＜0.001),while Ktrans,Ve and Kep were significantly higher than that of no lymph node metastasis group (P ＜0.001).With the increase of Dukes staging in rectal cancer,ADCmean was decreasing and Ktrans was increasing,with statistically significant difference (P ＜0.001);among which the ADCmean of Dukes A and B was significantly higher than that of Dukes C and D (P ＜ 0.05),and Ktrans was significantly lower than that of Dukes C and D (P ＜ 0.05).Ktrans and Kep were increased with the increased expression levels of Ki67 and CerbB-2,and the difference between Ktrans and Kep was statistically significant (P ＜ 0.05).The ADCmean decreased with the increase of Ki67 and CerbB-2 expression level,and the difference was statistically significant (P ＜ 0.05).Conclusions DCE-MRI quantitatively participates can reflect the biological behavior of rectal cancer,and can be used to evaluate the prognosis of tumors and guide the clinical selection of more appropriate treatment options.

Características y supervivencia de pacientes con cáncer de seno metastásico HER2-positivo en la era post-trastuzumab / Characteristics and survival of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era

Resumen Introducción: Existen múltiples factores pronóstico de la supervivencia en el cáncer de mama metastásico (CMM). Los dos factores mejor estudiados son la expresión de receptores hormonales (RH) y el estatus HER2, por lo que su determinación es obligada en toda paciente con diagnóstico de CMM. El 80% de los tumores expresan RH y el 20% son HER2-positivo. El objetivo de este estudio es determinar los factores pronóstico de la supervivencia global (SG) de pacientes con diagnóstico de CMM HER2-positivo atendidos entre 2009 y 2015 en el Instituto de Cancerología de Medellín (Colombia). Métodos: Estudio observacional retrospectivo. Se realizaron las curvas de supervivencia mediante el método de Kaplan-Meier comparadas con Log-Rank test y se analizaron los factores que influyeron en la supervivencia mediante la regresión de Cox. Resultados: Se incluyeron 101 pacientes. La mediana de seguimiento fue 46,6 meses (rango 13-155 meses), la SG a cinco años fue 41% (IC95%: 31%-50%) y a diez años 13% (IC95%: 4%-30%). Tuvieron mayor SG pacientes con enfermedad en recaída, con estadios I y II, las mayores de 40 años, menopáusicas, con tumores con grado histológico bajo y co-expresión de receptores hormonales. Las pacientes que recayeron tuvieron mayor SG que las que hicieron metástasis de novo (HR: 0,47, IC95%: 0,27-0,81) ajustado por las otras variables. Conclusiones: La supervivencia de estas pacientes fue semejante al de otros países, al igual que las líneas de tratamiento y la terapia recibida.

Abstract Introduction: There are multiple risk factors associated with the prognosis of survival of metastatic breast cancer (MBC). The two major risk factors are the expression of hormonal receptors (HR) and HER 2 neu, and the reason why they are requested in every MBC patient. The large majority (80%) of breast tumors are HR positive, and 20% are HER 2 positive. The aim of this study was to determine the prognostic factors associated with the overall survival (OS) of patients diagnosed with HER 2 positive MBC seen between January 2009 and December 2015 in the Instituto de Cancerología (Medellín-Colombia). Methods: A retrospective observational study was conducted, with survival analysis using the Kaplan-Meier method. The survival curves were compared using the Log-Rank Test, and factors associated with survival were analyzed using the Cox regression. Results: 101 patients were included in the study. The median survival time was 46.6 months (Range 13-155 months), the 5-year OS was 41% (95% CI; 31%-50%) and the 10-year OS 13% (95% CI; 4%-30%). Higher overall survival was found for patients with relapsed disease, those with stages I and II, patients older than 40 years, postmenopausal, tumors with low histological grade and with co-expression of hormonal receptors. The patients with relapse of disease had a higher OS than the de novo patients after being adjusted for the other factors (HR: 0.47, 95% CI; 0.27-0.1). Discussion: The overall survival time is similar to that of other countries, as well as the lines of treatment and therapy received.

Epidemiologic Study of Human Epidermal Growth Factor Receptor 2 Expression in Advanced/Metastatic Gastric Cancer: an Assessment of Human Epidermal Growth Factor Receptor 2 Status in Tumor Tissue Samples of Gastric and Gastro-Esophageal Junction Cancer

PURPOSE: The Trastuzumab for gastric cancer (GC) trial identified human epidermal growth factor receptor 2 (HER2) as a predictor of successful treatment with trastuzumab (HER2 receptor targeting agent) among patients with advanced/metastatic GC. To date, the prevalence of HER2 overexpression in the Korean population is unknown. The present study aimed to assess the incidence of HER2 positivity among GC and gastroesophageal (GE) junction cancer samples and the relationship between HER2 overexpression and clinicopathological characteristics in Korean patients. MATERIALS AND METHODS: Tumor samples collected from 1,695 patients with histologically proven GC or GE junction enrolled at 14 different hospitals in Korea were examined. After gathering clinicopathological data of all patients, HER2 status was assessed by immunohistochemistry (IHC) at each hospital, and IHC 2+ cases were subjected to silver-enhanced in situ hybridization at 3 central laboratories. RESULTS: A total of 182 specimens tested positive for HER2, whereas 1,505 tested negative. Therefore, the overall HER2-positive rate in this study was 10.8% (95% confidence interval: 9.3%–12.3%). The HER2-positive rate was higher among intestinal-type cases (17.6%) than among other types, and was higher among patients older than 70 years and 50 years of age, compared to other age groups. CONCLUSIONS: Our evaluation of the HER2 positivity rate (10.8%) among Korean patients with GC and GE junction indicated the necessity of epidemiological data when conducting studies related to HER2 expression in GC and GE junction.