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La importància d'una predicció acurada del tumor residual després de quimioteràpia neoadjuvant (QNA) radica en la planificació del tipus de cirurgia. Avui en dia es considera que la millor prova per a valorar la resposta a la QNA és la ressonància magnètica (RM); tot i això, estudis previs suggereixen que la fiabilitat de la RM pot estar alterada per diferents factors. En els últims anys la QNA ja no només s'utilitza amb intenció de millorar les opcions quirúrgiques de les pacients, sinó que s'ha ampliat a pacients amb tumors amb immunofenotips que tenen alta probabilitat d'assolir RCp, que en els subtipus triple negatiu (TN) i HER2(+), s'ha associat a millor pronòstic. Hem analitzat 186 pacients tractades amb QNA a l'Hospital del Mar entre 2006 i 2013. Totes les pacients disposaven de RM basal i de RM post-QNA. A la nostra sèrie predominaven tumors tipus Luminal (21% Luminal A i 33.3% Luminal B-HER2(-)). Hem assolit una taxa de Resposta Completa Patològica (RCp) total d'un 17.7%, que augmenta fins a un 66.7% en els tumors HER2(+) i que es redueix a un 0% en els tumors Luminal A. Hem objectivat que els principals factors predictors de RCp són estat de Receptors Hormonals (RH) i de HER2. Hem reportat una bona correlació entre mida de tumor residual valorada mitjançant RM i valorada per patologia, amb una mitjana de discrepança d'11.6 mm. L'immunofenotip on la mitjana de discrepança entre mides és menor és en el TN, de 3.2 mm versus un 15.4 mm en els tumors Luminal A, on trobem la major discrepança. Els factors que afecten a la precisió de la RM per a valorar mida tumoral residual són mida tumoral inicial i estat de HER2. Hem reportat una Sensibilitat de la RM per a predir RCp del 75.8%, una Especificitat del 79.7%, un Valor Predictiu Positiu del 44.6% i un Valor Predictiu Negatiu del 77.75%. La precisió de la RM per a detectar RCp és superior a mama que a aixella. La fiabilitat de la RM per a detectar RCp està influenciada pel valor basal de ki 67. L'immunofenotip on, In patients with breast cancer the assessment of the response to neoadjuvant chemotherapy (NAQ) is very important in order to plan the surgical treatment. Magnetic Resonance Imaging (MRI) is accepted as the best method to predict pathological response to NAQ. However, previous studies suggested that the accuracy of MRI in this situation can be altered by different factors. Initially NAQ was used to improve the surgical options of the patients, in recent years its used has been extended to patients with tumours with immunofenotypes that have a high probability of achieving pathological complete response (pCR), which is associated with better prognosis in triple negative (TN) and HER2 (+) subtypes. This retrospective study included 186 breast cancer patients treated with NAQ between January 2006 and June 2013 at Hospital del Mar. All patients underwent a baseline MRI and after NAQ. Luminal tumours predominated in our series (21% Luminal A and 33.3% Luminal B-HER2[-]). A pCR was achieved in 17.4% patients, 66.7% in HER(+) tumours, the highest, and 0% in Luminal A tumours, the lowest. The main predictors of pCR were Hormonal Receptors (RH) and HER2 status. We observed a good correlation between residual tumour size evaluated by MRI and tumour size evaluated by pathology, with a mean discrepancy of 11.6 mm. The size discrepancy was smaller in TN tumours, of 3.2 mm versus 15.4 mm in Luminal A tumors, where we find the greatest discrepancy. Initial tumor size and HER2 status were significantly correlated with the accuracy of MRI to asses residual tumour size. The overall sensitivity, specificity, positive predictive value and negative predictive value to predict pCR by using MRI were 75.8%, 79.7%, 44.6% and 77.75%. The accuracy of the MRI to detect pCR was superior in the breast that in the axilla. The accuracy of the MRI to detect pCR was influenced by the basal value of ki 67. The immunofenotype where the MRI better evaluated the response was the TN. We did not identifie

Objetives: Identify putative functional variants in the CYP11A1 and CYP17A1 genes associated with musculoskeletal effects (accelerated bone mass loss and arthralgia) derived from treatment with aromatase inhibitors (AI). Material and methods: The B-ABLE cohort is a prospective study of postmenopausal women with breast cancer undergoing AI treatment. Bone mineral density in the lumbar spine and femoral neck was measured by densitometry and joint pain using visual analogue scale. From single-nucleotide polymorphisms (SNPs) in genes CYP11A1 (rs4077581, rs11632698 and rs900798) and CYP17A1 (rs4919686, rs4919683, rs4919687, rs3781287, rs10786712, rs6163, rs743572), previously associated with musculoskeletal events, haplotypes were constructed for each pacient from the cohort, and those haplotypes that showed greatest phenotypic differences were chosen (p<0.05). Within each haplotype, patients with extreme phenotypes were chosen for the sequencing of respective genes and identifying functional genetic variants. Finally, a multiple linear regression analysis was carried out considering the models of dominant, recessive and additive genetic inheritance. Results: No mutation was found in coding regions. A genetic variant (D15S520), in the basal promoter region of gene CYP11A1, was found associated with femoral neck bone loss at 24 month of AI treatment. Conclusions: Variants in regulatory regions of the CYP11A1 gene could modulate the expression of this gene, thus explaining part of the phenotypic variability found in bone loss of patients undergoing AI treatment., Objetivos: Identificar putativas variantes funcionales en los genes CYP11A1 y CYP17A1 asociadas a efectos musculoesqueléticos (pérdida acelerada de la masa ósea y artralgias) derivados del tratamiento con inhibidores de la aromatasa (IA). Material y métodos: La cohorte B-ABLE es un estudio prospectivo de mujeres postmenopáusicas con cáncer de mama en tratamiento con IA. La densidad mineral ósea en columna lumbar y cuello femoral se midió mediante densitometría, y el dolor articular mediante escala analógica visual. A partir de polimorfismos de cambio de un nucleótido (SNPs) en los genes CYP11A1 (rs4077581, rs11632698 y rs900798) y CYP17A1 (rs4919686, rs4919683, rs4919687, rs3781287, rs10786712, rs6163, rs743572), asociados previamente con eventos musculoesqueléticos, se construyeron los haplotipos para cada paciente de la cohorte, y se seleccionaron aquellos que mostraron mayor diferencia fenotípica (p<0,05). Dentro de cada haplotipo, se eligieron aquellas pacientes con fenotipos extremos para la secuenciación de los respectivos genes y la identificación de variantes genéticas funcionales. Finalmente, se realizó un análisis de regresión lineal múltiple contemplando los modelos de herencia genética dominante, recesivo y aditivo. Resultados: No se encontró ninguna mutación en las regiones codificantes. En la región del promotor basal del gen CYP11A1 se encontró una variante genética (D15S520) asociada a la pérdida de masa ósea del cuello de fémur a los 24 meses de tratamiento con IA. Conclusiones: Variantes en regiones reguladoras del gen CYP11A1 podrían modular la expresión de este gen, explicando así parte de la variabilidad fenotípica encontrada en la pérdida de hueso de las pacientes en tratamiento con IA.

Objectives: The aim of this study was to analyze bone mineral density (BMD) changes throughout aromatase inhibitor (AI) treatment in clinical cases and also consider its association with the CYP11A1 gene and the BMD variation after treatment. Material and methods: The B-ABLE cohort is a prospective study of postmenopausal women with breast cancer, in AI treatment. BMD variation was analyzed during AI treatment, as well as the differences those patients who were treated and not treated previously with tamoxifen (TMX). Three polymorphisms (rs4077581, rs11632698 and rs900798) of the CYP11A1 gene were genotyped for their association with BMD variation. Results: TMX-treated patients presented more rapid BMD loss than those who did not undergo prior TMX treatment (60% less in spine and 46% in femur at 2 years and 70% less in the spine and 63% in the femur at 3 years). However, no significant BMD loss was detected after treatment in either group. The 3 CYP11A1 gene polymorphisms were significantly associated with BMD variation in the femur at the end of the treatment. Conclusions: BMD was reduced more rapidly in patients with prior TMX treatment than in those who only received AI, although no significant differences were detected after treatment. The 3 CYP11A1 gene polymorphisms were associated with BMD variation in response to AI treatment., Objetivos: El objetivo del estudio fue analizar los cambios en la densidad mineral ósea (DMO) a lo largo del tratamiento con inhibidores de aromatasa (IA) en la práctica clínica y evaluar la asociación entre el gen CYP11A1 y la variación de DMO al final del tratamiento. Material y métodos: La cohorte B-ABLE es un estudio prospectivo de mujeres postmenopáusicas con cáncer de mama, en tratamiento con IA. Se analizó la variación de DMO durante todo el tratamiento con IA, así como las diferencias entre las pacientes tratadas y no-tratadas previamente con tamoxifeno (TMX). Tres polimorfismos (rs4077581, rs11632698 y rs900798) del gen CYP11A1, fueron genotipados para su asociación con la variación de DMO. Resultados: Las pacientes tratadas con TMX mostraron pérdidas más aceleradas de DMO que las no tratadas previamente con TMX (60% menos en columna y 46% en fémur a los 2 años y 70% menos en columna y 63% en fémur a los 3 años). No obstante, al final del tratamiento no se detectaron diferencias significativas en la pérdida de DMO entre ambos grupos de pacientes. Los 3 polimorfismos del gen CYP11A1 resultaron significativamente asociados a la variación de DMO en fémur al final del tratamiento. Conclusiones: La DMO disminuyó de forma más acelerada en las pacientes con tratamiento previo con TMX que en las que solo recibieron AI, a pesar de que no se detectaron diferencias significativas al final de tratamiento. Polimorfismos en el gen CYP11A1 están relacionados con la variación de la DMO en respuesta al tratamiento con IA.