Imaginando el futuro / Looking to the future

Presentamos la visión futurista que de su especialidad tienen 7 líderes de opinión estrechamente comprometidos con la patología mamaria. Las especialidades incluidas fueron radiología, patología, cirugía, cirugía plástica, medicina nuclear, oncología médica y oncología radioterápica. Los autores plasman, en este artículo, sus opiniones y criterios respecto a los avances que vislumbran en su futuro profesional.Conceptos clave como sistemas de cribado sin radiación, transcriptómica clínica, diagnóstico funcional del tumor, inteligencia artificial, navegación intraoperatoria, biopsia líquida, ADN tumoral circulante, reconstrucción con técnicas microquirúrgicas avanzadas, hipofraccionamiento extremo o teragnosis, son algunos de los conceptos presentados y discutidos.Los autores justifican sus puntos de vista, abriendo líneas de trabajo a tener en cuenta para optimizar esfuerzos y el conocimiento futuro. (AU)

We present the futuristic vision of their specialty of seven opinion leaders closely involved in breast pathology. The specialties were radiology, pathology, surgery, plastic surgery, nuclear medicine, medical oncology, and radiation oncology. In this article, the authors express their opinions and criteria regarding the advances they foresee for their professional future.Key concepts such as radiation-free screening systems, clinical transcriptomics, functional tumor diagnosis, artificial intelligence, intraoperative navigation, liquid biopsy, circulating tumor DNA, reconstruction with advanced microsurgical techniques, extreme hypofractionation or theragnosis are some of the concepts presented and discussed.The authors justify their points of view, suggesting lines of work to optimize efforts and future knowledge. (AU)

Consenso de la Sociedad Española de Senología y Patología Mamaria (SESPM) sobre la biopsia selectiva del ganglio centinela (BSGC) y el manejo axilar en el cáncer de mama (2022) / Consensus of the Spanish Society of Breast Senology and Pathology (SESPM) on Selective Biopsy of the Sentinel Node (BSGC) and axylar management in breast cancer (2022)

La estadificación ganglionar inicial está indicada en aquellos casos de carcinoma de mama en los que la información obtenida pueda cambiar la actitud terapéutica o establecer una información pronóstica con implicaciones para el seguimiento de las pacientes.En los últimos años, los cambios conceptuales introducidos por ensayos clínicos y estudios observacionales han generado nuevos retos con disparidad de criterios respecto a la actitud terapéutica a seguir en determinados casos.Ello justifica la necesidad de revisar el último documento del Consenso de la SESPM del año 2013.Aunque el objetivo fundamental del documento es la actualización de la práctica clínica en ganglio centinela de cáncer de mama, los cambios acontecidos en los últimos años en el diagnóstico y el tratamiento de este tumor obligan a incluir aspectos que, aunque ajenos al ámbito estricto del procedimiento de la biopsia selectiva del ganglio centinela, se interrelacionan directamente con él. (AU)

Initial nodal staging is indicated in those cases of breast carcinoma in which the information obtained can change the therapeutic approach or establish prognostic information with implications for patient follow-up.In recent years, the conceptual changes introduced by clinical trials and observational studies have generated new challenges with disparity of criteria regarding the therapeutic approach to be followed in certain cases.This justifies the need to revise the latest consensus document of 2013.Although the main objective of the document is to update clinical practice in sentinel lymph node breast cancer, the changes that have occurred in recent years in the diagnosis and treatment of this tumor make it necessary to include aspects that, although outside the strict scope of the selective sentinel lymph node biopsy procedure, are directly related to it. (AU)

Genetic platforms: Do we do what we know? or do we know what we do? / Plataformas genéticas: ¿hacemos lo que sabemos? o ¿sabemos lo que hacemos?

Molecular and genomic pathology is an essential cornerstone of diagnosis in breast disease, to such an extent that genetic information is already included in therapeutic decision-making. There are now various commercial platforms available in the clinic, generally with little or no agreement in the genes included, in their technical basis, in the definition of risk groups, in the information they provide, in their indications or in the protocols required to use them. Objective To evaluate the use and knowledge of these platforms. Material and methods An eleven-question survey was conducted targeting breast units accredited by the SESPM in Spain at that time. Results 26 units out of the 36 surveyed responded and data was obtained that can guide the use of the platforms and serve as a starting point towards gaining a deeper knowledge of them. Conclusions The indications approved by the Autonomous Regions need to be re-evaluated. There is insufficient evidence to base decisions about the axilla on the platforms. MammaPrint® is the only platform with level of evidence 1a for N1–3 patients. It also identifies a subgroup of patients who may not require hormonal treatment. (AU)

La enfermedad molecular y genómica constituye un pilar irrenunciable del diagnóstico en enfermedad mamaria, de tal manera que la información genética ha sido ya integrada en la toma de decisiones terapéuticas. Actualmente, existen diferentes plataformas comerciales disponibles en la clínica, generalmente con pocas o nulas coincidencias en los genes incluidos, en su fundamento técnico, en la definición de grupos de riesgo, en la información que proporcionan, en sus indicaciones y en el circuito requerido para la realización de las mismas. Objetivo Evaluar el uso y conocimiento de dichas plataformas. Material y métodos Se realizó una encuesta de 11 preguntas dirigidas a las unidades de mama acreditadas en España por la SESPM en ese momento. Resultados Respondieron 26 unidades de 36 encuestadas y se obtuvieron datos que pueden ser orientativos acerca del uso de las plataformas y pueden servir como punto de partida para profundizar en su conocimiento. Conclusiones Es necesario re-evaluar indicaciones aprobadas por las CC.AA. No existe evidencia suficiente para tomar decisiones sobre la axila en función de la plataforma. MammaPrint® es la única plataforma con evidencia IA para pacientes N1-3. Además, identifica un subgrupo de pacientes que pueden no requerir tratamiento hormonal. (AU)

Axillary staging based on molecular analysis: Results of the B-CLOSER-II study.

INTRODUCTION: Axillary staging (pN) is a strong predictor of outcome in early stage breast cancer yet following the publication of the Z0011 trial there has been an increasing tendency to spare lymph node dissection. Automated molecular detection of cytokeratin 19mRNA by one-step nucleic acid amplification (OSNA) has been demonstrated to be an accurate method to assess sentinel lymph node (SLN) metastasis. In this study we compare histological and molecular methods following complete axillary lymph node dissection (cALND), determine whether molecular axillary staging affects survival, and evaluate the predictive and prognostic value of total tumor load in ALND (AD-TTL) and in all positive nodes (G-TTL). MATERIAL AND METHODS: Axillary lymph nodes were collected from 102 patients with primary breast cancer with histological confirmation of axillary involvement (cN+) or positive SLN. The central 1-mm portion of each non-SLN was processed for hematoxylin-eosin staining and the remaining tissue was analyzed by OSNA. RESULTS: Non-SLNs were diagnosed as positive in 72 out of 102 patients (70.6 %) on OSNA compared with only 53 (52 %) on histology (p < 0.01). Thirteen patients would have changed staging if the diagnoses provided had been by molecular methods (p < 0.01), but without a change in prognosis. AD-TTL and G-TTL were predictive of recurrence and mortality. CONCLUSIONS: Compared to molecular detection, histological examination significantly underestimates the frequency of axillary node metastases. However, the increase in pN did not show a clinical effect on survival in those patients.

Vía clínica de cáncer de mama de la Sociedad Española de Senología y Patología Mamaria: una visión preliminar / Clinical pathway for breast cancer of the Spanish Society of Senology and Breast Disease: a preliminary view

La Sociedad Española de Senología y Patología Mamaria, a través de un grupo de expertos, ha redactado la vía clínica de cáncer de mama que constituye una importante herramienta de mejora continua en la atención de la paciente. Consta de 2 matrices temporales, una de diagnóstico y otra de tratamiento, en las que se describen todos los aspectos relacionados con el diagnóstico y el tratamiento del cáncer de mama desde el punto de vista de las distintas especialidades, teniendo en cuenta la distribución temporal de los mismos. Acompañan a estas matrices toda una serie de tablas y documentos explicativos de cada fase. Además, incluye un listado de indicadores para la validación de los distintos procesos. El documento completo se publicará como una monografía de forma inminente y se distribuirá a todos los socios y a los especialistas relacionados con el manejo de la paciente con cáncer de mama

The Spanish Society of Senology and Breast Disease, through a group of experts, has drawn up a clinical pathway for breast cancer, which constitutes an important tool for continuous quality assurance in patient care. The pathway consists of 2 temporary matrices, one for diagnosis and the other for treatment, in which all aspects related to the diagnosis and treatment of breast cancer are described from the point of view of the different specialties, taking into account their temporal distribution. These matrices are accompanied by tables and explanatory documents for each phase. The document also includes a list of indicators for the validation of the different processes. The complete document will be published as a monograph in the near future and will be distributed to all members and specialists involved in the management of breast cancer patients

Human Papillomavirus in the region of La Ribera-Valencia: present and future / Virus del papiloma humano en la comarca de La Ribera-Valencia: presente y futuro

INTRODUCTION: Human Papillomavirus (HPV) is the main cause of cervical cancer. The etiology and effects derived from this infection are set by molecular techniques and cytological diagnosis, respectively. In the present study, data obtained by an opportunist screening of cervical cancer in La Ribera region are revised and related statistically. MATERIAL AND METHODS: Data considering different variables such as age, degree of lesion, HPV type detected and number of virus in coinfection were collected from 1,372 HPV positive cytology samples. HPV detection was carried out by means of three molecular techniques and the degree of lesion was analyzed by cytological diagnosis (Bethesda). In order to determine the relationship between different selected variables, several statistical analyses were performed. RESULTS: Only degree of lesion variable showed a direct relationship with the rest of variables, increasing with aging process, viral oncogenicity, presence of at least one high-risk virus and with the fact of being mono-infected. The probability of presenting a higher-level degree of lesion multiplied by 28.4 when high-risk HPV was detected in mono-infection. CONCLUSIONS: HPV molecular detection is the most suitable technique to perform a cervix cancer primary screening for the management of women with negative cytological diagnose. The number of detected types is statistically related to the degree of lesion. The establishment of a properly regulated screening to identify HPV infection, and therefore, of cervical cancer risk, is essential

INTRODUCCIÓN: El virus del papiloma humano (VPH) es la principal causa de cáncer cervical. La etiología y los efectos derivados de esta infección se establecen mediante técnicas moleculares y diagnóstico citológico, respectivamente. En el presente estudio, los datos obtenidos por un cribado oportunista de cáncer cervical en la comarca de La Ribera se revisaron y se relacionaron estadísticamente. MATERIAL Y MÉTODOS: Se recopilaron datos que incluyeron diferentes variables como la edad, el grado de lesión, el tipo de VPH detectado y el número de virus en coinfección de 1.372 citologías positivas para VPH. La detección del VPH se realizó mediante tres técnicas moleculares y el grado de lesión se analizó mediante diagnóstico citológico (Bethesda). Para determinar la relación entre las diferentes variables, se realizaron varios análisis estadísticos. RESULTADOS: Sólo la variable del grado de lesión mostró una relación directa con el resto de variables, aumentando con el proceso de envejecimiento, la oncogenicidad viral, la presencia de al menos un virus de alto riesgo y el hecho de estar mono-infectado. La probabilidad de presentar un mayor nivel de lesión se multiplicó por 28,4 cuando se detectó VPH de alto riesgo en la mono-infección. CONCLUSIONES: La detección molecular del VPH es la técnica más adecuada para realizar un cribado primario del cáncer de cuello uterino para el manejo de mujeres con diagnóstico citológico negativo. El número de tipos detectados está estadísticamente relacionado con el grado de lesión. El establecimiento de un cribado regulado adecuadamente para identificar la infección por VPH y, por lo tanto, del riesgo de cáncer cervical, es esencial

HER2 immunohistochemistry inter-observer reproducibility in 205 cases of invasive breast carcinoma additionally tested by ISH.

Assessment of HER2 biomarker in invasive breast carcinoma patients allows a specific therapeutic approach. Clinical guidelines indicate immunohistochemistry (IHC) and in situ hybridization (ISH) to test HER2, however both have drawbacks which results in low reproducibility of results especially in equivocal cases. Our main objective is to quantify inter-observer IHC reproducibility and cross it with the ISH result. Our series includes 205 invasive breast carcinoma cases sent for ISH retest from 14 hospitals, 5 observers to assess the IHC and 2 observers for the ISH of each case. We found that the observers only achieve an absolute agreement for IHC in 1 out of 3 cases. The inter-observer concordance for IHC is low (0.2 ≤ k ≤ 0.4) or moderate (0.41 ≤ k ≤ 0.6). In ISH positive cases the concordance for IHC is higher than in the ISH negative cases. In conclusion, the study shows low and moderate IHC inter-observer concordance, finding the more worrying values among the ISH negative cases which are the most part of this particular sample. Subjective interpretation of the techniques, among other factors, has negative impact in HER2 evaluation. To offset this limitation we have checked that reaching a consensus from different observers for HER2 IHC assessment improves the results.

Modelo predictivo de metástasis en ganglios axilares no centinela en cáncer de mama. Variables emergentes. Estudio MOTTO, parte I / Predictive model of breast cancer metastasis in axillary non-sentinel lymph nodes. Emergent variables. The MOTTO study, part I

INTRODUCCIÓN: La carga tumoral total (CTT) obtenida del estudio OSNA de cada uno de los ganglios centinela ha sido identificada como el predictor más potente de metástasis en ganglios linfáticos axilares no centinela. Por otra parte, los distintos subtipos moleculares (SM) de cáncer de mama difieren entre ellos de forma significativa no solo en términos de incidencia, pronóstico y tratamiento, sino también respecto al patrón de afectación metastásica axilar. Nuestra hipótesis consiste en que la predicción de enfermedad metastásica en la linfadenectomía axilar puede mejorar aplicando un modelo predictivo basado en la CTT y el subtipo intrínseco del tumor. OBJETIVO: Evaluar el impacto del SM subrogado inmunohistoquímicamente en la predicción metastásica de los ganglios axilares no centinela con base en la CTT. MATERIAL Y MÉTODOS: Estudio retrospectivo, multicéntrico europeo, que incluye 683 pacientes procedentes de 9 hospitales. RESULTADOS: El análisis univariante identificó 6 variables independientes que correlacionan significativamente con la afectación metastásica axilar no centinela. De ellas, las variables valor logarítmico de la CTT, diámetro tumoral y SM diagnosticado por inmunohistoquímica fueron seleccionadas para el modelo multivariante. Las odds ratio estimadas por el modelo fueron valor logarítmico de la CTT 1.527 (IC 95% 1.299-1.796), diámetro tumoral 1.503 (IC 95% 1.062-2.129) y SM 2.195 (IC 95% 1.246-3.867). CONCLUSIONES: El SM, la CTT y el diámetro tumoral son los predictores más potentes de afectación axilar y deben ser incluidos en los algoritmos diagnósticos como variables esenciales para la toma de decisiones terapéuticas sobre la axila

INTRODUCTION: The total tumour load (TTL) obtained from OSNA study in each of the sentinel lymph nodes has been identified as the most powerful predictor of axillary non-sentinel lymph node metastasis. In addition, the distinct molecular subtypes (MS) of breast cancer differ significantly not only in terms of incidence, prognosis and treatment but also in terms of the pattern of axillary metastatic involvement. We hypothesised that the prediction of metastatic disease in axillary lymphadenectomy could be enhanced by applying a predictive model based on the TTL and the intrinsic tumour subtype. OBJECTIVE: To evaluate the impact of the MS identified by immunohistochemistry on prediction of metastatic disease in axillary non-sentinel lymph nodes based on TTL. MATERIAL AND METHODS: Retrospective, European multicenter study including 683 patients from 9 hospitals. RESULTS: Univariate analysis identified 6 variables that were significantly correlated with axillary non-sentinel metastasis. Of these, the variables logarithmic value of the TTL, tumour diameter and MS diagnosed by immunohistochemistry were selected for multivariate analysis. The odds ratio estimated by the model were: logarithmic value of the TTL 1.527 (95% CI: 1.299-1.796), tumour diameter 1.503 (95% CI: 1.062-2.129) and MS 2.195 (95% CI: 1.246-3.867). CONCLUSIONS: The strongest predictors of axillary involvement were MS, TTL and tumour diameter. These variables should be included in diagnostic algorithms as essential parameters for therapeutic decision-making on the axilla

Linfoma anaplásico de células grandes asociado a implantes mamarios. Documento de consenso (I): epidemiología, patogenia, clínica y diagnóstico / Breast-implant associated anaplastic large-cell lymphoma. Consensus document (I). Epidemiology, pathogenesis, symptoms and diagnosis

El linfoma anaplásico de células grandes asociado a implantes mamarios (BIA-ALCL según sus siglas en inglés) es un tipo raro de linfoma no Hodgkin que se ha descrito en el contexto de la cirugía reconstructiva y estética de mama mediante implantes. Estos artículos presentan un consenso de la Sociedad Española de Senología y Patología Mamaria (SESPM) con la idea de unificar, en esta primera parte, los criterios de diagnóstico de esta enfermedad describiendo asimismo la epidemiología y la etiopatogenia

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare type of non-Hodgkin lymphoma that has been described in the context of reconstructive and aesthetic breast implant surgery. These articles present a consensus of the Spanish Society of Senology and Breast Disease (SESPM). In this first part, the aim is to unify the diagnostic criteria of this disease and describe its epidemiology and etiopathogenesis

Linfoma anaplásico de células grandes asociado a implantes mamarios. Documento de consenso parte II: estadificación, tratamiento, pronóstico y seguimiento / Breast implant-associated anaplastic large-cell lymphoma. Consensus document part II: Staging, prognosis and follow-up

El linfoma anaplásico de células grandes asociado a implantes mamarios (BIA-ALCL según sus siglas en inglés) es un tipo raro de linfoma no Hodgkin que se ha descrito en el contexto de la cirugía reconstructiva y estética de mama mediante implantes. Este segundo artículo presenta la parte del consenso de la Sociedad Española de Senología y Patología Mamaria (SESPM) sobre el tratamiento quirúrgico, médico, radioterápico, pronóstico y seguimiento

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare type of non-Hodgkin lymphoma that has been described in the context of breast implant reconstructive and cosmetic surgery. This second article presents the consensus of the Spanish Society of Senology and Breast Disease (SESPM) on the medical and surgical treatment of this disease, radiotherapy, prognosis and follow-up

Creciendo juntos. Casos equívocos HER2 y guías clínicas / Growing up together. HER2 equivocal cases and clinical guidelines

El diagnóstico del biomarcador HER2 es un factor imprescindible en el manejo de los pacientes de carcinoma infiltrante de mama. La sobreexpresión del HER2, observada en aproximadamente el 15% de los pacientes, se asocia a mal pronóstico. La determinación del HER2 se realiza o bien por IHQ, o bien por HIS, siendo ambas técnicas válidas, intercambiables y necesarias para los casos equívocos. Las guías clínicas ASCO/CAP son un instrumento útil para la estandarización y mejora del diagnóstico, sin embargo, tienen sus puntos débiles; por ejemplo, la categoría de resultados equívocos genera inconvenientes en la práctica clínica. Al tratarse de documentos vivos y cambiantes, estas guías son susceptibles de cambio bajo la luz de nuevas observaciones. Se realiza el estudio de 3 series consecutivas y distintas de 1.568 casos HER2 equívocos (IHQ 2+) de carcinoma infiltrante de mama, procedentes de distintos hospitales españoles. El objetivo de este estudio es comparar los resultados de HIS obtenidos, en nuestro centro de referencia, al aplicar las distintas guías clínicas para el HER2 (2007 y 2013), además de comparar distintas técnicas de HIS entre sí (CISH e IQ-FISH). Nuestros resultados indican que la aplicación de la guía 2013 aumenta el porcentaje (%) de resultados equívocos respecto a la del 2007. Y también nos permiten afirmar que cualquiera de las 2 técnicas de HIS es válida para el estudio del HER2 (AU)

HER2 biomarker assessment is essential for the correct management of invasive breast carcinoma. Overexpression of HER2, observed in approximately 15% of the patients, is associated with a bad prognosis. HER2 determination can be carried out either by IHQ or by HIS as both are valid, interchangeable and necessary techniques for equivocal cases. Although the clinical guidelines ASCO/CAP are a useful tool for diagnostic standardization and improvement, they have drawbacks; for instance, the category of equivocal results can create problems in routine clinical practice. As they are on-going documents, they are susceptible to change in the light of new observations. We studied three consecutive and different series of 1,568 HER2 equivocal invasive breast carcinoma (IHQ 2+), from different Spanish hospitals. The aim of this study was to compare both the ISH results in our laboratory when applying the different clinical guidelines for the HER2 (2007 and 2013) and the different ISH techniques (CISH and IQ-FISH). Our results indicate that the use of the 2013 guidelines increases the percentage of equivocal results with respect 2007. We confirmed that both of the ISH techniques are valid for the study of the HER2 biomarker (AU)

Control de calidad de la citología ginecológica. Programa de Calidad de la Sociedad Española de Citología. Resultados de la primera ronda / Quality control of Gynecologic cytology program of the Spanish sicuety for Cytology. Results of the first round

Introducción. Las recomendaciones del cribado de cáncer de cérvix en España incluyen la participación en programas de control de calidad externos a los laboratorios de citología. La Sociedad Española de Citología ha iniciado un programa de control de calidad de la citología ginecológica. Objetivo. Presentar y discutir los resultados de la primera ronda del control de calidad de la Sociedad Española de Citología. Material y método. Organización de los hospitales participantes según el tipo de citología. Intercambio de preparaciones de 50 casos entre los participantes: 10 negativos, 20 ASCUS-ASCH, 10 LSIL y 10 HSIL. Estudio de la correlación diagnóstica interobservador. Resultados. Trece hospitales participantes: 6 en ThinPrep, 5 en triple toma y 2 en SurePath. La concordancia global media fue del 69,7%. La concordancia media por tipo de lesión fue del 41,7%. La concordancia en negativos fue del 78,1%, en ASCUS del 41,3%, en LSIL de 58,9% y en HSIL del 64,2%. Los casos discordantes se diagnosticaban con mayor frecuencia como negativos, ASCUS y LSIL. Las discordancias severas (HSIL/ASCH versus negativo), alcanzaron un 3,8% de casos. Conclusiones. Nuestros resultados son similares a los descritos en la literatura con muy escasas discordancias severas. El método de intercambio de laminillas utilizado no permite una formación continuada posterior, ya que no incluye la revisión de los casos con discordancias diagnósticas. Por ello, se contemplan correcciones metodológicas en sucesivas rondas (AU)

Introduction. The Spanish guidelines for cervical cancer screening recommend participating in external quality control programs. The Spanish Society of Cytology has started its own program of quality control for gynecological cytology. Aim. To describe and discuss the results of the first round of The Spanish Society of Cytology quality control for gynecological cytology. Material and method. Organization of participating hospitals on the basis of cytology type. Exchange of diagnostic slides from 50 cases among participants, as follows: 10 negative; 20 ASCUS-ASCH, 10 LSIL and 10 HSIL. Analysis of inter-observer correlation. Results. 13 hospitals took part: 6 with ThinPrep liquid-based cytology, 5 with conventional cytology, and 2 with SurePath liquid-based cytology. The global mean concordance was 69.7%. The mean concordance in the type of lesion was 41.7%. The concordance was 78.1% in negative diagnoses, 41.3%, in ASCUS, 58.9% in LSIL and 64.2% in HSIL The discordant cases were diagnosed more frequently as negative, ASCUS and LSIL. 3.8% of cases showed major discordances (HSIL or ASCH versus negatives). onclusions. Our results are similar to those reported in the literature, with very little severe discordance. The method of exchanging slides does not allows continuous training, since the review of discordant cases can not be made. Therefore, methodological corrections are contemplated for future rounds (AU)

Role of total tumour load of sentinel lymph node on survival in early breast cancer patients.

BACKGROUND: Axillary staging (pN) is considered one of the most important prognostic factors in breast cancer patients. However, the Z0011 study data drastically reduced the number of surgical axillary dissections in a selected group of patients, limiting the prognostic information relating to axillary involvement to the sentinel lymph node (SLN). It is known that there is a relationship between SLN total tumour load (TTL) and axillary involvement. The objective of this study is to analyse the relationship between the TTL and outcomes in patients with early stage breast cancer. PATIENTS AND METHODS: clinicopathological and follow-up data were collected from 950 patients with breast cancer between 2009 and 2010 on whom SLN analysis was conducted by molecular methods (One Step Nucleic Acid Amplification, Sysmex, Kobe, Japan). RESULTS: TTL (defined as the total number of CK19 mRNA copies in all positive SLN) correlates with disease free survival (HR, 1.08; p = 0.000004), with local recurrence disease free survival (HR = 1.07; p = 0.0014) and overall survival (HR: 1.08, p = 0.0032), clearly defining a low-risk group (TTL <2.5 × 104 CK19 mRNA copies/µL) versus a high-risk group (>2.5 × 104 CK 19 mRNA copies/µL). CONCLUSIONS: SLN TTL permits the differentiation between two patient groups in terms of DFS and OS, independently of axillary staging (pN), age and tumour characteristics (size, grade, lymphovascular invasion). This new data confirms the clinical value of low axillary involvement and could partially replace the information that staging of the entire axilla provides in patients on whom no axillary lymph node dissection is performed.

Elaboration of a nomogram to predict nonsentinel node status in breast cancer patients with positive sentinel node, intraoperatively assessed with one step nucleic amplification: Retrospective and validation phase.

BACKGROUND: Tumor-positive sentinel lymph node (SLN) biopsy results in a risk of non sentinel node metastases in micro- and macro-metastases ranging from 20 to 50%, respectively. Therefore, most patients underwent unnecessary axillary lymph node dissections. We have previously developed a mathematical model for predicting patient-specific risk of non sentinel node (NSN) metastases based on 2460 patients. The study reports the results of the validation phase where a total of 1945 patients were enrolled, aimed at identifying a tool that gives the possibility to the surgeon to choose intraoperatively whether to perform or not axillary lymph node dissection (ALND). METHODS: The following parameters were recorded: Clinical: hospital, age, medical record number; Bio pathological: Tumor (T) size stratified in quartiles, grading (G), histologic type, lymphatic/vascular invasion (LVI), ER-PR status, Ki 67, molecular classification (Luminal A, Luminal B, HER-2 Like, Triple negative); Sentinel and non-sentinel node related: Number of NSNs removed, number of positive NSNs, cytokeratin 19 (CK19) mRNA copy number of positive sentinel nodes stratified in quartiles. A total of 1945 patients were included in the database. All patient data were provided by the authors of this paper. RESULTS: The discrimination of the model quantified with the area under the receiver operating characteristics (ROC) curve (AUC), was 0.65 and 0.71 in the validation and retrospective phase, respectively. The calibration determines the distance between predicted outcome and actual outcome. The mean difference between predicted/observed was 2.3 and 6.3% in the retrospective and in the validation phase, respectively. The two values are quite similar and as a result we can conclude that the nomogram effectiveness was validated. Moreover, the ROC curve identified in the risk category of 31% of positive NSNs, the best compromise between false negative and positive rates i.e. when ALND is unnecessary (<31%) or recommended (>31%). CONCLUSIONS: The results of the study confirm that OSNA nomogram may help surgeons make an intraoperative decision on whether to perform ALND or not in case of positive sentinel nodes, and the patient to accept this decision based on a reliable estimation on the true percentage of NSN involvement. The use of this nomogram achieves two main gools: 1) the choice of the right treatment during the operation, 2) to avoid for the patient a second surgery procedure.

Cuando la axila se torna molecular / When the axilla shifts towards molecular

No disponible

Molecularly determined total tumour load in lymph nodes of stage I-II colon cancer patients correlates with high-risk factors. A multicentre prospective study.

Stage I-II (pN0) colorectal cancer patients are surgically treated although up to 25 % will eventually die from disease recurrence. Lymph node (LN) status is an independent prognostic factor in colorectal cancer (CRC), and molecular tumour detection in LN of early-stage CRC patients is associated with an increased risk of disease recurrence and poor survival. This prospective multicentre study aimed to determine the relationship between LN molecular tumour burden and conventional high-risk factors in stage I-II colon cancer patients. A total of 1940 LN from 149 pathologically assessed pN0 colon cancer patients were analysed for the amount of tumour cytokeratin 19 (CK19) messenger RNA (mRNA) with the quantitative reverse transcription loop-mediated isothermal amplification molecular assay One-Step Nucleic Acid Amplification. Patient's total tumour load (TTL) resulted from the sum of all CK19 mRNA tumour copies/µL of each positive LN from the colectomy specimen. A median of 15 LN were procured per case (IQR 12;20). Molecular positivity correlated with high-grade (p < 0.01), mucinous/signet ring type (p = 0.017), male gender (p = 0.02), number of collected LN (p = 0.012) and total LN weight per case (p < 0.01). The TTL was related to pT stage (p = 0.01) and tumour size (p < 0.01) in low-grade tumours. Multivariate logistic regression showed independent correlation of molecular positivity with gender, tumour grade and number of fresh LN [AUC = 0.71 (95 % CI = 0.62-0.79)]. Our results show that lymph node CK19 mRNA detection correlates with classical high-risk factors in stage I-II colon cancer patients. Total tumour load is a quantitative and objective measure that may help to better stage early colon cancer patients.

Modelo predictivo multiparamétrico del estatus axilar en pacientes con cáncer de mama: carga tumoral total y perfil molecular. Estudio multicéntrico / A multiparametric predictive model of axillary status in patients with breast cancer: total tumoral load and molecular signature. A multicenter study

Objetivo. El objetivo de nuestro estudio es evaluar el impacto combinado de cada uno de los perfiles moleculares del cáncer de mama, subrogados inmunohistoquímicamente junto con la carga tumoral total del ganglio centinela como predictores de afectación metastásica en los ganglios axilares no centinela. Material y métodos. Se incluyeron 373 pacientes de carcinoma infiltrante de mama con ganglio centinela metastásico y linfadenectomía axilar, procedentes de seis hospitales españoles. Se aplicaron los criterios de ST Gallen para definir el perfil molecular. Se realizó un análisis multivariante para definir diferentes modelos predictivos y se estudiaron las distribuciones de densidad de probabilidad de la carga tumoral para cada perfil molecular en los casos con axila metastásica y no metastásica en los ganglios no centinela. Resultados. Hubo un 66% de linfadenectomías axilares metastásicas. Se obtuvieron 7 modelos predictivos cuyas áreas bajo la curva ROC oscilaron entre 0,65 y 0,77. El mejor modelo fue el basado en la carga tumoral total, tipo histológico, diámetro tumoral, grado, invasión linfovascular, perfil molecular y número total de ganglios centinela. Las mayores diferencias de densidad de probabilidad de la carga tumoral total se producen entre las distribuciones de casos positivos y negativos de los perfiles moleculares BH, TN y HER2. Conclusión. La inclusión del perfil molecular en el modelo mejora el área bajo la curva ROC, especialmente si se incluye también el número total de cganglios centinela. Se observan diferencias entre los distintos perfiles moleculares para el valor predictivo de la carga tumoral total (AU)

Objective. To evaluate the combined impact of each of the immunohistochemically surrogated molecular signatures (PM) of breast cancer subtype along with the total tumor load (CTT) of the sentinel node (SN) as a predictor of non-SN metastatic involvement. Methods. We included 373 patients diagnosed with infiltrating breast cancer with metastatic SN who underwent subsequent axillary lymph node dissection (ALND) from six hospitals. The surrogate MS for each case was defined as per ST Gallen definitions. A multivariate analysis was conducted to estimate the predictive model and normal kernel functions to fit the density distributions of the total tumoral load for each molecular signatures. Results. Metastatic involvement of the axillary lymph node was identified in 66% of the patients. We obtained seven different predictive models with an area under curve (AUC) ranging from 0.65 to 0.77. The best model was based on the CTT, histological type, tumor size, stage, lymphatic invasion, MS, and the total number of SN. The greatest differences in the density functions of the CTT were found in the PM for positive and negative cases of the BH, TN and HER2 subtypes. Conclusions. The inclusion of PM in the multivariate model improved the AUC, especially when the total number of sentinel nodes were included. Differences were observed in the impact of the CTT among the different smolecular profiles subtypes (AU)