Mujeres con cáncer de mama: evaluación del afecto positivo y negativo y valoración de un programa de Intervención psicológica en el ámbito hospitalario

[email protected] la actualidad hay numerosos estudios que demuestran que la intervención psicológica es benefi ciosa para los pacientes con cáncer. Nuestro objetivo es investigar el efecto intra- sujetos de la intervención psicológica sobre el afecto positivo y negativo durante los ciclos de tratamiento de quimioterapia adyuvante en mujeres con cáncer de mama. Además estudiamos el efecto de la interacción entre la psicoterapia y la resistencia/vulnerabilidad psicológica de las pacientes en las mismas variables dependientes. Método: La muestra está formada por 119 pacientes diagnosticadas de un cáncer de mama localizado que recibieron tratamiento adyuvante con quimioterapia. Todas las pacientes fueron evaluadas y recibieron intervención psicológica a lo largo del tratamiento. Las variables dependientes: el afecto positivo y negativo fueron evaluadas en cinco intervalos: previamente al tratamiento quimioterápico, 2º, 4º, 6º ciclo de quimioterapia y a los dos meses post-tratamiento. El factor entresujetos resistencia/vulnerabilidad psicológica se derivó de un Análisis de Cluster a partir de cuatro medidas, pre y post, de ansiedad y depresión. Los instrumentos de evaluación utilizados fueron la Escala de Afecto Positivo y Negativo (Sánchez-Cánovas, 1994), y la Escala Hospitalaria de Ansiedad y Depresión (HADS) de Zigmond y Snaith (1983). Se realizó análisis descriptivo de los datos, Análisis Múltiple de la Varianza (MANOVA) de medias repetidas para la comparación intra-sujetos y el diseño factorial mixto para la comparación entre-sujetos (resistentes /vulnerables) Resultados: muestran el efecto principal intra-sujetos de la intervención psicológica en el afecto positivo (p<0.05), no existiendo efecto de la interacción entre la intervención psicológica y la resistencia/vulnerabilidad psicológica. Respecto del afecto negativo, el efecto de la intervención psicológica intra-sujetos y la interacción de ésta con los grupos de pacientes resistentes/vulnerables es signifi cativo en ambos casos (p<0.05). Los contrastes intrasujetos entre los 5 intervalos muestran diferencias signifi cativas entre el intervalo del pretratamiento (1ª evaluación) y el 2º ciclo de quimioterapia (2ª evaluación) en el afecto positivo y negativo. Conclusiones: La ganancia más importante se obtiene en la primera intervención psicológica y ésta es crucial para el mantenimiento del estado de ánimo positivo y la disminución del afecto negativo de las pacientes. Hay ganancia en los dos grupos, las pacientes vulnerables son las que más mejoría experimentan. Es importante señalar la importancia de esta primera intervención y la repercusión que tiene frente a las contingencias aversivas que supone los sucesivos ciclos de quimioterapia.Currently there are numerous publications demonstrating that psychological intervention in patients with cancer is benefi cial. Our objective is to study the within-subjects effect of the psychological intervention on the positive and negative affect during adjuvant chemotherapy cycles in women with breast cancer. In addition, we study the effect of the interaction between psychotherapy and psychological resistance/ vulnerability of patients on the same dependent variables. Method: The sample consists of 119 patients diagnosed with a localized breast cancer that received adjuvant chemotherapy treatment. All the patients were evaluated and received psychological intervention throughout the treatment. Dependent variables: positive and negative affect were evaluated in fi ve intervals: chemotherapy pre-treatment, second, fourth, sixth cycle of chemotherapy and two month post-treatment. The two groups of resistant and vulnerable patients were divided by Cluster Analysis of two measures of anxiety and depression before and after of chemotherapy. Measures used were the Positive and Negative Affect Scale (Sánchez- Cánovas, 1994) and the Hospital Anxiety and Depression Scale (HADS) of Zigmond and Snaith (1983). Descriptive analysis of data and a multivariate analysis of variance with repeated-measures (MANOVA-RM) were performed to compare within-subjects and the mixed factorial design to compare betweensubjects (resistant/vulnerable). Results: demonstrate the main within-subjects effect of the psychological intervention in the positive affect (p<0.05), existing no effect between psychological intervention and psychological resistance /vulnerability interaction. In relation to the negative affect, the effect of the within-subjects psychological intervention and its interaction with the resistant/vulnerable group of patients is signifi cant in both cases (p<0.05). Within-subjects contrasts among the fi ve intervals show signifi cant differences between the pre-treatment interval (fi rst evaluation) and the second cycle of chemotherapy (second evaluation) in the negative and positive affect. Conclusions: The most important benefi t is obtained in the fi rst psychological intervention which is crucial to maintain a positive mood state and diminish the negative affect of patients. There is benefi t in both groups; however, the vulnerable patients present more improvement. Moreover, it is worth mentioning the importance of this fi rst intervention and its repercussion in response to aversive contingencies of chemotherapy cycles

Women with breast cancer: positive and negative affect assessment and psychological intervention program in the hospital area

En la actualidad hay numerosos estudios que demuestran que la intervención psicológica es beneficiosa para los pacientes con cáncer. Nuestro objetivo es investigar el efecto intra-sujetos de la intervención psicológica sobre el afecto positivo y negativo durante los ciclos de tratamiento de quimioterapia adyuvante en mujeres con cáncer de mama. Además estudiamos el efecto de la interacción entre la psicoterapia y la resistencia/vulnerabilidad psicológica de las pacientes en las mismas variables dependientes. Método: La muestra está formada por 119 pacientes diagnosticadas de un cáncer de mama localizado que recibieron tratamiento adyuvante con quimioterapia. Todas las pacientes fueron evaluadas y recibieron intervención psicológica a lo largo del tratamiento. Las variables dependientes: el afecto positivo y negativo fueron evaluadas en cinco intervalos: previamente al tratamiento quimioterápico, 2º, 4º, 6º ciclo de quimioterapia y a los dos meses post-tratamiento. El factor entresujetos resistencia/vulnerabilidad psicológica se derivó de un Análisis de Cluster a partir de cuatro medidas, pre y post, de ansiedad y depresión. Los instrumentos de evaluación utilizados fueron la Escala de Afecto Positivo y Negativo (Sánchez-Cánovas, 1994), y la Escala Hospitalaria de Ansiedad y Depresión (HADS) de Zigmond y Snaith (1983). Se realizó análisis descriptivo de los datos, Análisis Múltiple de la Varianza (MANOVA) de medias repetidas para la comparación intra-sujetos y el diseño factorial mixto para la comparación entre-sujetos (resistentes /vulnerables) Resultados: muestran el efecto principal intra-sujetos de la intervención psicológica en el afecto positivo (p&lt;0.05), no existiendo efecto de la interacción entre la intervención psicológica y la resistencia/vulnerabilidad psicológica. Respecto del afecto negativo, el efecto de la intervención psicológica intra-sujetos y la interacción de ésta con los grupos de pacientes resistentes/vulnerables es significativo en ambos casos (p&lt;0.05). Los contrastes intra-sujetos entre los 5 intervalos muestran diferencias significativas entre el intervalo del pre-tratamiento (1ª evaluación) y el 2º ciclo de quimioterapia (2ª evaluación) en el afecto positivo y negativo. Conclusiones: La ganancia más importante se obtiene en la primera intervención psicológica y ésta es crucial para el mantenimiento del estado de ánimo positivo y la disminución del afecto negativo de las pacientes. Hay ganancia en los dos grupos, las pacientes vulnerables son las que más mejoría experimentan. Es importante señalar la importancia de esta primera intervención y la repercusión que tiene frente a las contingencias aversivas que supone los sucesivos ciclos de quimioterapia.Currently there are numerous publications demonstrating that psychological intervention in patients with cancer is beneficial. Our objective is to study the within-subjects effect of the psychological intervention on the positive and negative affect during adjuvant chemotherapy cycles in women with breast cancer. In addition, we study the effect of the interaction between psychotherapy and psychological resistance/ vulnerability of patients on the same dependent variables. Method: The sample consists of 119 patients diagnosed with a localized breast cancer that received adjuvant chemotherapy treatment. All the patients were evaluated and received psychological intervention throughout the treatment. Dependent variables: positive and negative affect were evaluated in five intervals: chemotherapy pre-treatment, second, fourth, sixth cycle of chemotherapy and two-month post-treatment. The two groups of resistant and vulnerable patients were divided by Cluster Analysis of two measures of anxiety and depression before and after of chemotherapy. Measures used were the Positive and Negative Affect Scale (Sánchez-Cánovas, 1994) and the Hospital Anxiety and Depression Scale (HADS) of Zigmond and Snaith (1983). Descriptive analysis of data and a multivariate analysis of variance with repeated-measures (MANOVA-RM) were performed to compare within-subjects and the mixed factorial design to compare betweensubjects (resistant/vulnerable). Results: demonstrate the main within-subjects effect of the psychological intervention in the positive affect (p&lt;0.05), existing no effect between psychological intervention and psychological resistance /vulnerability interaction. In relation to the negative affect, the effect of the within-subjects psychological intervention and its interaction with the resistant/vulnerable group of patients is significant in both cases (p&lt;0.05). Within-subjects contrasts among the five intervals show significant differences between the pre-treatment interval (first evaluation) and the second cycle of chemotherapy (second evaluation) in the negative and positive affect. Conclusions: The most important benefit is obtained in the first psychological intervention which is crucial to maintain a positive mood state and diminish the negative affect of patients. There is benefit in both groups; however, the vulnerable patients present more improvement. Moreover, it is worth mentioning the importance of this first intervention and its repercussion in response to aversive contingencies of chemotherapy cycles

PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer

To identify a group of patients who might benefit from the addition of weekly paclitaxel to conventional anthracycline-containing chemotherapy as adjuvant therapy of node-positive operable breast cancer. The predictive value of PAM50 subtypes and the 11-gene proliferation score contained within the PAM50 assay were evaluated in 820 patients from the GEICAM/9906 randomized phase III trial comparing adjuvant FEC to FEC followed by weekly paclitaxel (FEC-P). Multivariable Cox regression analyses of the secondary endpoint of overall survival (OS) were performed to determine the significance of the interaction between treatment and the (1) PAM50 subtypes, (2) PAM50 proliferation score, and (3) clinical and pathological variables. Similar OS analyses were performed in 222 patients treated with weekly paclitaxel versus paclitaxel every 3 weeks in the CALGB/9342 and 9840 metastatic clinical trials. In GEICAM/9906, with a median follow up of 8.7 years, OS of the FEC-P arm was significantly superior compared to the FEC arm (unadjusted HR = 0.693, p = 0.013). A benefit from paclitaxel was only observed in the group of patients with a low PAM50 proliferation score (unadjusted HR = 0.23, p < 0.001; and interaction test, p = 0.006). No significant interactions between treatment and the PAM50 subtypes or the various clinical–pathological variables, including Ki-67 and histologic grade, were identified. Finally, similar OS results were obtained in the CALGB data set, although the interaction test did not reach statistical significance (p = 0.109). The PAM50 proliferation score identifies a subset of patients with a low proliferation status that may derive a larger benefit from weekly paclitaxel. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-013-2416-2) contains supplementary material, which is available to authorized users

PAM50 Breast Cancer Subtyping by RT-qPCR and Concordance with Standard Clinical Molecular Markers

Abstract Background Many methodologies have been used in research to identify the “intrinsic” subtypes of breast cancer commonly known as Luminal A, Luminal B, HER2-Enriched (HER2-E) and Basal-like. The PAM50 gene set is often used for gene expression-based subtyping; however, surrogate subtyping using panels of immunohistochemical (IHC) markers are still widely used clinically. Discrepancies between these methods may lead to different treatment decisions. Methods We used the PAM50 RT-qPCR assay to expression profile 814 tumors from the GEICAM/9906 phase III clinical trial that enrolled women with locally advanced primary invasive breast cancer. All samples were scored at a single site by IHC for estrogen receptor (ER), progesterone receptor (PR), and Her2/neu (HER2) protein expression. Equivocal HER2 cases were confirmed by chromogenic in situ hybridization (CISH). Single gene scores by IHC/CISH were compared with RT-qPCR continuous gene expression values and “intrinsic” subtype assignment by the PAM50. High, medium, and low expression for ESR1, PGR, ERBB2, and proliferation were selected using quartile cut-points from the continuous RT-qPCR data across the PAM50 subtype assignments. Results ESR1, PGR, and ERBB2 gene expression had high agreement with established binary IHC cut-points (area under the curve (AUC) ≥ 0.9). Estrogen receptor positivity by IHC was strongly associated with Luminal (A and B) subtypes (92%), but only 75% of ER negative tumors were classified into the HER2-E and Basal-like subtypes. Luminal A tumors more frequently expressed PR than Luminal B (94% vs 74%) and Luminal A tumors were less likely to have high proliferation (11% vs 77%). Seventy-seven percent (30/39) of ER-/HER2+ tumors by IHC were classified as the HER2-E subtype. Triple negative tumors were mainly comprised of Basal-like (57%) and HER2-E (30%) subtypes. Single gene scoring for ESR1, PGR, and ERBB2 was more prognostic than the corresponding IHC markers as shown in a multivariate analysis. Conclusions The standard immunohistochemical panel for breast cancer (ER, PR, and HER2) does not adequately identify the PAM50 gene expression subtypes. Although there is high agreement between biomarker scoring by protein immunohistochemistry and gene expression, the gene expression determinations for ESR1 and ERBB2 status was more prognostic

Predicting response and survival in chemotherapy-treated triple-negative breast cancer

BACKGROUND: In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC). METHODS: Gene expression and clinical-pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated. RESULTS: Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55-81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival. CONCLUSIONS: The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not

Two-dimensional arrangements of bis(haloethynyl)benzenes combining halogen and hydrogen interactions

The electronic distribution of some haloethynylbenzene derivatives may favor the formation of two-dimensional organizations by combining halogen and hydrogen bonds. In order to highlight this strategy, we have prepared seven cocrystals and analyzed their structures. 1,4-Bis(iodoethynyl)benzene, 1,4-bis(bromoethynyl)benzene, and 1,3-bis(iodoethynyl)benzene were used as halogen bond donors and 1,2-bis(4-pyridyl)ethylene, pyridazine, propanone, hexamethylenetetramine, and 2,8-dimethyl-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine (Tröger’s base) were employed as halogen bond acceptors. The crystal structures of seven halogen-bonded complexes show C–X···Y (X = I, Br; Y = N, O) distances shorter than the sum of the van der Waals radii, and six of them contain the edge-to-edge C–H···X (X = I, Br) supramolecular hydrogen bond synthon. The stabilization energies with basis set superposition error correction of hydrogen bond synthons have been determined by DFT calculations, and they are in the range 2.9 to 5.7 kcalmol–1. To gain a deeper understanding of these interactions, noncovalent interaction methodology was also applied.Thanks are given to Crystallography Service from the University of Zaragoza (Spain), University of Pais Vasco (Spain), and National University of Singapore. This work was supported by the Ministerio de Economia y Competitividad, under the projects MAT2012-38538-C03-01, MAT2014- 55205-P, Fondo Europeo de Desarrollo Regional (FEDER), and Gobierno de Aragon. L.G. thanks the Ministerio Economia y Competitividad and J.M. thanks Ministerio de Educacion Cultura y Deporte for a grant (FPU14/06003).Peer reviewe

PAM50 Breast Cancer Subtyping by RT-qPCR and Concordance with Standard Clinical Molecular Markers

Background: Many methodologies have been used in research to identify the “intrinsic” subtypes of breast cancer commonly known as Luminal A, Luminal B, HER2-Enriched (HER2-E) and Basal-like. The PAM50 gene set is often used for gene expression-based subtyping; however, surrogate subtyping using panels of immunohistochemical (IHC) markers are still widely used clinically. Discrepancies between these methods may lead to different treatment decisions. Methods We used the PAM50 RT-qPCR assay to expression profile 814 tumors from the GEICAM/9906 phase III clinical trial that enrolled women with locally advanced primary invasive breast cancer. All samples were scored at a single site by IHC for estrogen receptor (ER), progesterone receptor (PR), and Her2/neu (HER2) protein expression. Equivocal HER2 cases were confirmed by chromogenic in situ hybridization (CISH). Single gene scores by IHC/CISH were compared with RT-qPCR continuous gene expression values and “intrinsic” subtype assignment by the PAM50. High, medium, and low expression for ESR1, PGR, ERBB2, and proliferation were selected using quartile cut-points from the continuous RT-qPCR data across the PAM50 subtype assignments. Results ESR1, PGR, and ERBB2 gene expression had high agreement with established binary IHC cut-points (area under the curve (AUC) ≥ 0.9). Estrogen receptor positivity by IHC was strongly associated with Luminal (A and B) subtypes (92%), but only 75% of ER negative tumors were classified into the HER2-E and Basal-like subtypes. Luminal A tumors more frequently expressed PR than Luminal B (94% vs 74%) and Luminal A tumors were less likely to have high proliferation (11% vs 77%). Seventy-seven percent (30/39) of ER-/HER2+ tumors by IHC were classified as the HER2-E subtype. Triple negative tumors were mainly comprised of Basal-like (57%) and HER2-E (30%) subtypes. Single gene scoring for ESR1, PGR, and ERBB2 was more prognostic than the corresponding IHC markers as shown in a multivariate analysis. Conclusions The standard immunohistochemical panel for breast cancer (ER, PR, and HER2) does not adequately identify the PAM50 gene expression subtypes. Although there is high agreement between biomarker scoring by protein immunohistochemistry and gene expression, the gene expression determinations for ESR1 and ERBB2 status was more prognostic.Medical Oncology, Division ofMedicine, Faculty ofNon UBCMedicine, Department ofReviewedFacult