Características clínicas e histopatológicas asociadas a pacientes con Cáncer de Mama Triple Negativo en un Hospital de Referencia peruano, 2012- 2018 / Clinical and histopathological characteristics associated with patients with triple-negative Breast cancer at a national reference hospital, 2012 - 2018

Objetivo: Determinar las características clínicas e histopatológicas asociadas a las pacientes con cáncer de mama triple negativo (CMTN) en un Hospital peruano de referencia. Métodos: Estudio transversal, analítico. Se revisaron las historias clínicas de todas las pacientes atendidas en el Hospital Nacional Hipóito Unanue durante el periodo de junio del 2012 a junio del 2018. Resultados: Se incluyeron 134 pacientes de los cuales 36 (26,9%) correspondieron a CMTN, el estadío clínico más frecuente fue el III y II para los dos grupos. El tipo histológico que más predomino fue el tipo ductal infiltrante en ambos grupos. El grado histológico elevado fue característico en los casos de CMTN (58%) a diferencia de los No TN. Los CMTN fueron de mayor tamaño (5,75 cm vs 3cm en no TN), y el Ki 67 fue más elevado en el TN (35% en comparación con el No TN con 15%). Se determinó en el análisis bivariado que el tamaño (RP: 1,4, IC: 1,17-1,68, p= 0,0001), Ki 67 (RP: 1,05, IC: 1,03-1,07, p= 0,001), IMC ≥25 kg/m2 (RP: 1,14, IC: 1,23-6,22, p= 0,014) y el Grado Histológico 3 (RP:3,87, IC: 1,74-8,63, p= 0,001) se asociaron significativamente a la presencia de CMTN. En el análisis multivariado se encontró que el grado 3 (RP: 1,74, IC: 1,01-3, p= 0,0046) y el Ki 67 (RP: 1,02, IC: 1,01-1,03, p= 0,0001) fueron las características histopatológicas asociados al CMTN. Conclusión: Las características más consistentemente asociadas al cáncer de mama triple negativo en fueron el elevado grado histológico y mayor valor de Ki67.

Objective:To determine the clinical and histopathological characteristics associated to patients with triple negative breast cancer of the Hipolito Unanue National Hospital between June 2012 to June 2018. Methods: Cross-sectional, analytical study. We reviewed the medical records of all patients treated at the Hipóito Unanue National Hospital during the period from June 2012 to June 2018. Results: 134 patients were included, out of which 36 (26.9%) were TN and 98 No TN. Of the histopathological characteristics, the most frequent CD was III and II for the two groups. The histological type that predominated was the infiltrating ductal type in both groups. The high histological grade was characteristic in NT (58%) unlike non TN. The NTs were larger 5.75 cm in contrast to the TNs with 3 cm, and the Ki 67 was higher in the TN 35% in contrast to the NON TN with 15%. In the bivariate analysis the size (RP: 1.4, CI: 1.17-1.68, p = 0.0001), Ki 67 (RP: 1.05, CI: 1.03-1.07, p = 0.001), BMI ≥25 kg / m2 ( RP: 1.14, CI: 1.23-6.22, p = 0.014), Histological Grade 3 (RP: 3.87, CI: 1.74-8.63, p = 0.001), size ≥5 cm (RP: 2.94, CI: 1.33-6.48, p = 0.008) were significant. I n the multivariate analysis it was found that grade 3 (PR: 1.74, CI: 1.01-3, p = 0.0046) and Ki 67 (RP: 1.02, CI: 1.01-1.03, p = 0.0001) were histopathological characteristics associated with CMTN. Conclusion: There are histopathological characteristics associated with triple negative breast cancer particularly high histological grade and Ki67 value.

In vivo phosphoproteomics reveals kinase activity profiles that predict treatment outcome in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) lacks prognostic and predictive markers. Here, we use high-throughput phosphoproteomics to build a functional TNBC taxonomy. A cluster of 159 phosphosites is upregulated in relapsed cases of a training set (n = 34 patients), with 11 hyperactive kinases accounting for this phosphoprofile. A mass-spectrometry-to-immunohistochemistry translation step, assessing 2 independent validation sets, reveals 6 kinases with preserved independent prognostic value. The kinases split the validation set into two patterns: one without hyperactive kinases being associated with a >90% relapse-free rate, and the other one showing ≥1 hyperactive kinase and being associated with an up to 9.5-fold higher relapse risk. Each kinase pattern encompasses different mutational patterns, simplifying mutation-based taxonomy. Drug regimens designed based on these 6 kinases show promising antitumour activity in TNBC cell lines and patient-derived xenografts. In summary, the present study elucidates phosphosites and kinases implicated in TNBC and suggests a target-based clinical classification system for TNBC.