Santisteban, M. (Marta)

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    Sellado antibiótico de catéteres intravasculares centrales. Presentación de un caso tipo y de un protocolo de sellado antibiótico
    (Servicio de Publicaciones de la Universidad de Navarra, 2002) Leiva, J. (José); Pozo, J.L. (José Luis) del; Santisteban, M. (Marta); García-del-Barrio, M.A. (M.A.); Lamata, M. (M.)
    El uso de catéteres intravasculares tunelizados centrales supone una aportación fundamental a la medicina moderna. La infección asociada a estos dispositivos es una de las causas más frecuentes de infección nosocomial en nuestro medio. La simple retirada de un catéter infectado puede ser suficiente para el control de la infección, sin embargo, en muchos casos esta retirada es problemática. En este trabajo se presenta un protocolo de sellado antibiótico aplicable a pacientes diagnosticados de infección asociada a catéter.
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    Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed
    (BioMed Central, 2014) Gil-Bazo, I. (Ignacio); Patiño-García, A. (Ana); Arevalo, E. (Estefanía); Rodriguez-Ruiz, M.E. (María Esperanza); Castañón-Álvarez, E. (Eduardo); Santisteban, M. (Marta); Rolfo, C. (Christian); Zubiri, L. (Leire); Lopez, I. (Inés); Salgado, J. (Josefa); Martin, P. (Patricia); Collado, V. (Víctor)
    BACKGROUND: We studied whether thymidylate synthase (TS) genotype has an independent prognostic/predictive impact on a European population of advanced non-small cell lung cancer (NSCLC) patients receiving pemetrexed. METHODS: Twenty-five patients treated with pemetrexed-based regimens were included. Genomic DNA was isolated prior to treatment. The variable number of tandem repeat (VNTR) polymorphisms, the G > C single nucleotide polymorphisms (SNP) and the TS 6-bp insertion/deletion (6/6) in the 3' untranslated region (UTR) polymorphisms were analyzed and correlated with overall response rate (ORR), progression-free survival (PFS), overall-survival (OS) and toxicity. RESULTS: The genotype +6/+6 predicted a higher ORR among active/former smokers compared to +6/-6 genotype (100% vs. 50%; p = 0.085). Overall, the 3R/3R genotype predicted a higher ORR (100%) over the rest VNTR polymorphisms (p = 0.055). The presence of 3R/3R genotype significantly correlated with a superior ORR in patients without EGFR activating mutations (100%) compared to 2R/2R, 2R/3R and 3R/4R genotype (77.8%, 33.3% and 0% respectively; p = 0.017). After a median follow-up of 21 months, a trend towards a better PFS, although not significant, was found among subjects showing 3R/3R polymorphisms (p = 0.089). A significantly superior OS was found in patients showing 3R/3R genotype rather than other VNTR polymorphisms (p = 0.019). No significant correlation with the toxicity was observed. CONCLUSION: In our series, 3R/3R polymorphism correlated with a superior OS. Also, this polymorphism, when associated to wild type EGFR, was related to a higher ORR to pemetrexed. Toxicity was not significantly correlated with a specific TS genotype.
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    Diagnostic utility of snail in metaplastic breast carcinoma
    (BioMed Central, 2010) Sookhan, N. (Nicole); Bryant, S.C. (Sandra C.); Degnim, A. (Amy); Santisteban, M. (Marta); Boughey, J.C. (Judy C.); Nassar, A. (Aziza); Giorgadze, T. (Tamar)
    Metaplastic breast carcinoma (MBC) is a rare subtype of breast cancer characterized by coexistence of carcinomatous and sarcomatous components. Snail is a nuclear transcription factor incriminated in the transition of epithelial to mesenchymal differentiation of breast cancer. Aberrant Snail expression results in lost expression of the cell adhesion molecule E-cadherin, an event associated with changes in epithelial architecture and invasive growth. We aimed to identify the utility of Snail, and of traditional immunohistochemical markers, in accurate MBC classification and to evaluate clinicopathologic characteristics and outcome.We retrospectively reviewed 34 MBC cases from January 1997 to September 2007. The control group contained 26 spindle cell lesions. Immunohistochemistry used Snail, p63, epidermal growth factor receptor (EGFR), OSCAR, and wide spectrum cytokeratin (WS-KER). Negative was a score less than 1%. We found that Snail and EGFR are sensitive (100%) markers with low specificity (3.8% and 19.2%) for detecting MBC. p63 and WS-KER are specific (100%), with moderate sensitivity (67.6% and 76.5%); OSCAR is sensitive (85.3%) and specific (92.3%). A combination of any 2 of the p63, OSCAR, and WS-KER markers increased sensitivity and specificity. MBCs tended to be high-grade (77%), triple negative (negative for estrogen receptor, progesterone receptor, and HER2) [27/33; 81.8%], and carcinomas with low incidence of axillary lymph node involvement (15%), and decreased disease-free [71% (95%CI: 54%, 94%) at 3 yrs.) and overall survival. A combination of p63, OSCAR and WS-KER are useful in its work-up. On the other hand, Snail is neither a diagnostic nor a prognostic marker for MBC.
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    Assessing the impact of the addition of dendritic cell vaccination to neoadjuvant chemotherapy in breast cancer patients: A model-based characterization approach
    (Wiley, 2019) Espinos, J. (Jaime); Pérez-Solans, B. (Belén); Lopez-Diaz-de-Cerio, A. (Ascensión); Troconiz, I.F. (Iñaki F.); Santisteban, M. (Marta); Elizalde, A. (Arlette); Inoges, S. (Susana); Pina-Insausti, L. (Luis); Salgado, E. (Esteban); Mejías-Sosa, L.D. (Luis D.)
    Aims: Immunotherapy is a rising alternative to traditional treatment in breast cancer (BC) patients in order to transform cold into hot immune enriched tumours and improve responses and outcome. A computational modelling approach was applied to quantify modulation effects of immunotherapy and chemotherapy response on tumour shrinkage and progression-free survival (PFS) in naïve BC patients. Methods: Eighty-three Her2-negative BC patients were recruited for neoadjuvant chemotherapy with or without immunotherapy based on dendritic cell vaccination. Sequential tumour size measurements were modelled using nonlinear mixed effects modelling and linked to PFS. Data from another set of patients (n = 111) were used to validate the model. Results: Tumour size profiles over time were linked to biomarker dynamics and PFS. The immunotherapy effect was related to tumour shrinkage (P < .05), with the shrinkage 17% (95% confidence interval: 2-23%) being higher in vaccinated patients, confirmed by the finding that pathological complete response rates in the breast were higher in the vaccinated compared to the control group (25.6% vs 13.6%; P = .04). The whole tumour shrinkage time profile was the major prognostic factor associated to PFS (P < .05), and therefore, immunotherapy influences indirectly on PFS, showing a trend in decreasing the probability of progression with increased vaccine effects. Tumour subtype was also associated with PFS (P < .05), showing that luminal A BC patients have better prognosis. Conclusions: Dendritic cell-based immunotherapy is effective in decreasing tumour size. The semi-mechanistic validated model presented allows the quantification of the immunotherapy treatment effects on tumour shrinkage and establishes the relationship between the dynamics of tumour size and PFS.
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    Tratamiento hormonal del cáncer de mama
    (Ediciones Universidad de Navarra, 2008) Espinos, J. (Jaime); Olier, C. (Clara); Santisteban, M. (Marta); Garcia-Foncillas, J. (Jesús); Hernandez, A. (A.); Cruz, S. (S.) de la; Fernandez-Hidalgo, Ó. (Óscar); Reyna, C. (Carmen)
    Hormonal therapy has been the first systemic treatment against breast cancer. Up to now Tamoxifen and ovarian supression/ablation were the best optionts we had to treat early breast cancer as advancer disease. The advent of aromatase inhibitors, new SERMS and antistrogen Fulvestrant have supoused a great advance in the treatment of this disease and at the same time have complicated the election of the optimal drug for each patient. This article tries to review the aviable treatment options insiting on its indications.
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    Palbociclib combined with endocrine therapy in heavily pretreated HR+/HER2(-) advanced breast cancer patients: Results from the compassionate use program in Spain (PALBOCOMP)
    (Elsevier, 2020) Manso, L. (Luis); Servitja, S. (Sónia); Llombart-Cussac, A. (Antonio); Bratos, R. (Raquel); Ruiz-Borrego, M. (Manuel); Gonzalez-Cao, M. (María); Echarri, M.J. (María J.); Gonzalez-Cortijo, L. (Lucía); Vega, E. (Estela); Gallegos, I. (Isabel); Hernando, B.A. (Blanca A.); Robles, C.E. (Carlos E.); Oliveira, M. (Mafalda); Galan, M. (María); Andres, R. (Raquel); Santisteban, M. (Marta); Alvarez-Busto, I. (Iñaki); Alés-Martínez, J.E. (José E.); Rodríguez, C.A. (C.A.); Echeverría, I. (Isabel); Moreno, F. (Fernando); Delgado-Mingorance, J. (Juan I.); Oltra, A. (Amparo); Blanch, S. (Salvador); Legeren, M. (Marta); Hernando, C. (Cristina); García-Garre, E. (Elisa); Aguirre, E. (Elena); Galve, E. (Elena); Ballesteros, A. (Ana); Reboredo, C. (Cristina); Lopez, R. (Rafael); Morales, S. (Serafín); Malón, D. (Diego); Cabrera, M.A. (Miguel A.)
    Background: This study evaluated efficacy and safety of palbociclib, a CDK4/6 inhibitor, in heavilypretreated hormone receptor-positive and human epidermal growth factor receptor 2-negative (HRþ/ HER2- ) metastatic breast cancer (mBC) patients during the compassionate use program in Spain from February 2015 to November 2017. Patients and methods: Patient data were collected retrospectively from 35 hospitals in Spain. Patients with HRþ/HER2- mBC who had progressed on 4 treatments for advanced disease were eligible. Results: A total of 219 patients received palbociclib in combination with aromatase inhibitors (110; 50.2%), fulvestrant (87; 39.7%), tamoxifen (8; 3.6%) or as single agent (10; 4.6%). Mean age of the patients was 58 years; 31 patients (16.1%) were premenopausal and 162 (83.9%) were postmenopausal at the beginning of treatment with palbociclib. Patients had received a median of 3 previous lines of endocrine therapy (ET) for advanced disease. Real-world tumor response (rwTR) and clinical benefit rate were 5.9% (n ¼ 13) and 46.2% (n ¼ 101), respectively. The median real world progression-free survival (rwPFS) was 6.0 months (95% CI 5.7e7.0) and the median overall survival was 19.0 months (95% CI 16.4e21.7). Subgroup analysis revealed a significant difference in median rwPFS in patients treated with palbociclib plus fulvestrant depending on the duration of prior treatment with fulvestrant monotherapy (>6 versus 6 months; HR 1.93, 95% CI 1.37e2.73, p < 0.001). The most frequently reported toxicities were neutropenia, asthenia, thrombopenia and anemia. Conclusions: Palbociclib can be an effective and safe treatment option in patients with heavily pretreated endocrine-sensitive mBC, especially in those with longer PFS to previous ET.
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    Hábitos de sueño saludable, melatonina y cáncer de mama
    (Gobierno de Navarra, 2019) Santisteban, M. (Marta)
    En la actualidad es conocido que un estilo de vida saludable (actividad física aeróbica, dieta mediterránea, minimización de hábitos tóxicos y equilibrio emocional o una vida con un nivel de estrés aceptable) reduce el riesgo de padecer cáncer, pudiendo prevenir el cáncer en general y el de mama en particular. Un ritmo sueño-vigilia adecuado es imprescindible para conseguir un descanso reparador, y la falta de sueño asociada a una disrupción de biorritmos circadianos se ha relacionado con un mayor riesgo de sufrir cáncer de mama (CM) en mujeres.
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    Binge Drinking and Risk of Breast Cancer: Results from the SUN (‘Seguimiento Universidad de Navarra’) Project
    (2020) Gardeazabal, I. (Itziar); Martinez-Gonzalez, M.A. (Miguel Ángel); Romanos-Nanclares, A. (Andrea); Sanchez-Bayona, R. (Rodrigo); Toledo, E. (Estefanía); Bes-Rastrollo, M. (Maira); Santisteban, M. (Marta); Gea, A. (Alfredo)
    Alcohol intake is associated with the risk of breast cancer. Different patterns of alcoholdrinking may have different effects on breast cancer even when keeping constant the total amount of alcohol consumed. We aimed to assess the association between binge drinking and breast cancer risk. The SUN Project is a Spanish dynamic prospective cohort of university graduates initiated in 1999. In the 556-item lifestyle baseline questionnaire a validated food-frequency questionnaire was embedded. Participants completed biennial follow-up questionnaires. Cox regression models were used to estimate the hazard ratio (HR) for breast cancer associated with the exposure to binge drinking. A stratified analysis was performed according to menopausal status. We included 9577 women (mean age = 34 years, SD = 10 years), with a median follow-up of 11.8 years. Among 104,932 women-years of follow-up, we confirmed 88 incident cases of breast cancer. Women in the binge drinking group showed a higher risk of breast cancer (HR = 1.76; 95% CI: 1.03–2.99) compared to women in the non-binge drinking category. In the stratified analysis, a 2-fold higher risk for premenopausal breast cancer was associated with binge drinking habit (HR = 2.06; 95% CI: 1.11–3.82). This study adds new evidence on the association of binge drinking with breast cancer risk.
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    A novel BRCA1 mutation in a patient with breast and ovarian cancer: A case report
    (Spandidos Publications, 2013) Patiño-García, A. (Ana); Gil, C. (Carmen); Viedma, A. (Adriana); Gutierrez, C. (Cristina); Santisteban, M. (Marta); Salgado, J. (Josefa); Robles, M. (Maitane)
    Germline mutations in the human breast cancer genes BRCA1 and BRCA2 account for a substantial proportion of familial, early-onset breast and ovarian cancers. The present study reports a novel disease-causing BRCA1 mutation, nucleotide 3020insCT/c.2901insCT, in a 55-year-old Spanish female with breast and ovarian cancer. This frameshift mutation creates a premature stop codon at amino acid 1000, leading to a truncated BRCA1 protein. To the best of our knowledge, this mutation has not been previously described in the Breast Cancer Information Core (BIC) database or the published literature
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    MRI fused with prone FDG PET/CT improves the primary tumour staging of patients with breast cancer
    (Springer, 2017) Prieto, E. (Elena); Ribelles, M.J. (María Jesús); Martinez-Regueira, F. (Fernando); Rodriguez-Spiteri, N. (Natalia); Sancho, L. (Lidia); Santisteban, M. (Marta); Elizalde, A. (Arlette); Garcia-Velloso, M. J. (María José); Fernandez-Montero, A. (Alejandro); Idoate, M.A. (Miguel Ángel); Pina, L. (Luis); Rodriguez, M. (Macarena)
    Objective: Our aim was to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) fused with prone 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in primary tumour staging of patients with breast cancer. Methods: This retrospective study evaluated 45 women with 49 pathologically proven breast carcinomas. MRI and prone PET-CT scans with time-of-flight and point-spread-function reconstruction were performed with the same dedicated breast coil. The studies were assessed by a radiologist and a nuclear medicine physician, and evaluation of fused images was made by consensus. The final diagnosis was based on pathology (90 lesions) or follow-up ≥ 24 months (17 lesions). Results: The study assessed 72 malignant and 35 benign lesions with a median size of 1.8 cm (range 0.3-8.4 cm): 31 focal, nine multifocal and nine multicentric cases. In lesion-by-lesion analysis, sensitivity, specificity, positive and negative predictive values were 97%, 80%, 91% and 93% for MRI, 96%, 71%, 87%, and 89% for prone PET, and 97%. 94%, 97% and 94% for MRI fused with PET. Areas under the curve (AUC) were 0.953, 0.850, and 0.983, respectively (p < 0.01). Conclusions: MRI fused with FDG-PET is more accurate than FDG-PET in primary tumour staging of breast cancer patients and increases the specificity of MRI.