La parte y el todo. El principio de incertidumbre de Heisenberg / The parts of the sum and the sum: Heisenberg's uncertainty principle

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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)

mRNA in situ hybridization (HistoSonda): a new diagnostic tool for HER2-status in breast cancer-a multicentric Spanish study.

Monoclonal therapies could represent baseline-personalized medicine for patients with neoplasia. One of the most successful examples is Trastuzumab, a humanized antibody against epidermal growth factor receptor 2. Human epidermal growth factor receptor 2 (HER2) is a trans-membrane tyrosine kinase coded by the gene HER2/neu and overexpressed in approximately 12% to 20% of infiltrating breast carcinomas. The overexpression of HER2 is an independent adverse prognostic factor in relation to survival and is also predictive of response to treatment. Therefore, the correct evaluation of HER2 status is essential for the management of infiltrating breast carcinoma to determine the response to Trastuzumab. The most common evaluation technique is immunohistochemistry, which is confirmed by fluorescent or chromogenic monochrome or dual-gene in situ hybridization in ambiguous cases (immunohistochemical 2+). Our objective was to evaluate the diagnostic value of a new technique on the basis of HER2 mRNA in situ hybridization (HistoSonda) and study its correlation with immunohistochemistry and dual-chromogenic in situ hybridization (DUO-CISH) in 403 cases of infiltrating breast carcinoma. The percentage of DUO-CISH amplification was 25.8%, HistoSonda positivity was 31.2%, and positivity for Hercep-Test was 48.1%, including (+2) and (+3). Comparisons were made of each of the techniques, HistoSonda to IHQ and HistoSonda to DUO-CISH. The overall concordance between DUO-CISH and HistoSonda was 89%. Our data support the consistency of HistoSonda as a useful tool to determine HER2 status in breast cancer.

Breast cancer sentinel lymph node and axillary lymphadenectomy: new tools for new challenges.

Axillary lymph node status at the time of diagnosis is the most important prognostic indicator for women with breast cancer, and may influence management decisions. However, at present its role is controversial, as some groups recommend avoiding axillary lymph node dissection (ALND) in cases with metastasis of any size in the sentinel lymph nodes. Molecular analysis allows full examination of the sentinel lymph nodes in a short time period, discriminatation between macrometastasis, micrometastasis and isolated tumor cells, and helps to predict the performance of ALND. ALND may be the treatment of choice in some patients, even in cases of low-volume metastasis, as chemotherapy does not control regional disease well. In addition, the collection of metastatic cells, as well as the local immune surveillance, is susceptible to further molecular studies that will offer prognostic and predictive information, which may have an impact on therapeutic decisions, so that individualized treatments can be adequately designed.