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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    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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    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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    Leisure-time physical activity, sedentary behavior, and risk of breast cancer: Results from the SUN (‘Seguimiento Universidad De Navarra’) project
    (Elsevier, 2021) Gardeazabal, I. (Itziar); Martinez-Gonzalez, M.A. (Miguel Ángel); Romanos-Nanclares, A. (Andrea); Sanchez-Bayona, R. (Rodrigo); Toledo, E. (Estefanía); Santisteban, M. (Marta); Ruiz-Canela, M. (Miguel); Fernández-Lázaro, C.I. (César I.); Gea, A. (Alfredo); Álvarez-Álvarez, I. (Ismael)
    Evidence is still limited on the influence of sedentary lifestyles on breast cancer (BC) risk. Also, prospective information on the combined effects of both sedentariness and leisure-time physical activity (LTPA) is scarce. We aimed to assess the association of higher sedentary behavior and LTPA (separately and in combination) with the risk of BC in a middle-aged cohort of university graduates. The SUN Project is a follow-up study initiated in 1999 with recruitment permanently open. Baseline assessments included a validated questionnaire on LTPA and sedentary habits. Subsequently, participants completed biennial follow-up questionnaires. Multivariable adjusted Cox models were used to estimate the hazard ratios (HR) for incident BC according to LTPA, TV-watching, the joint classification of both, and a combined 8-item multidimensional active lifestyle score. We included 10,812 women, with 11.8 years of median follow-up of. Among 115,802 women-years of follow-up, we confirmed 101 incident cases of BC. Women in the highest category of LTPA (>16.5 MET-h/week) showed a significantly lower risk of BC (HR = 0.55; 95% CI: 0.34–0.90) compared to women in the lowest category (≤6 MET/h-week). Women watching >2 h/d of TV sh owed a higher risk (HR = 1.67; 95% CI:1.03–2.72) than those who watched TV <1 h/d. Women in the highest category (6–8 points) of the multidimensional combined 8-item score showed a lower BC risk (HR = 0.35; 95% CI: 0.15–0.79) than those in the lowest category (<2 points) group. There was no significant supra-multiplicative interaction between TV-watching and LTPA. Both low LTPA and TV-watching >2 h/d may substantially increase BC risk, independently of each other.
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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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    Final results regarding the addition of dendritic cell vaccines to neoadjuvant chemotherapy in early HER2-negative breast cancer patients: clinical and translational analysis
    (Sage Journals, 2021) Hato-Álvaro, L. (Laura); Rodríguez-Espiteri, N. (Natalia); Pérez-Solans, B. (Belén); Sanchez-Bayona, R. (Rodrigo); Lopez-Diaz-de-Cerio, A. (Ascensión); Urrizola-Martínez, A. (Amaia); Toledo, E. (Estefanía); Santisteban, M. (Marta); Inoges, S. (Susana); Salgado, E. (Esteban); Mejías-Sosa, L.D. (Luis D.); Idoate, M.A. (Miguel Ángel); Olartecoechea, B. (Begoña)
    Background:Primary breast cancer (BC) has shown a higher immune infiltration than the metastatic disease, justifying the optimal scenario for immunotherapy. Recently, neoadjuvant chemotherapy (NAC) combined with immune checkpoint inhibitors has demonstrated a gain in pathological complete responses (tpCR) in patients with BC. The aim of our study is to evaluate the safety, feasibility, and efficacy of the addition of dendritic cell vaccines (DCV) to NAC in HER2-negative BC patients. Methods:Thirty-nine patients with early BC received DCV together with NAC conforming the vaccinated group (VG) and compared with 44 patients as the control group (CG). All patients received anthracyclines and taxanes-based NAC (ddECx4→Dx4) followed by surgery ± radiotherapy ± hormonotherapy. Results:The tpCR rate was 28.9% in the VG and 9.09% in the CG (p = 0.03). Pathological CR in the triple negative (TN) BC were 50.0% versus 30.7% (p = 0.25), 16.6% versus 0% in luminal B (p = 0.15), and none among luminal A patients in VG versus CG, respectively. Impact of DCV was significantly higher in the programmed cell death ligand 1 (PD-L1) negative population (p < 0.001). PD-L1 expression was increased in patients with residual disease in the VG as compared with the CG (p < 0.01). No grade ⩾3 vaccine-related adverse events occurred. With a median follow-up of 8 years, no changes were seen in event-free survival or overall survival. Phenotypic changes post DCV in peripheral blood were observed in myeloid-derived suppressor cells (MDSC), NK, and T cells. Increase in blood cell proliferation and interferon (IFN)-γ production was detected in 69% and 74% in the VG, respectively. Humoral response was also found. Clonality changes in TCR-β repertoire were detected in 67% of the patients with a drop in diversity index after treatment. Conclusion:The combination of DCV plus NAC is safe and increases tpCR, with a significant benefit among PD-L1-negative tumors. DCV modify tumor milieu and perform cellular and humoral responses in peripheral blood with no impact in outcome. Trial registration:ClinicalTrials.gov number: NCT01431196. EudraCT 2009-017402-36.
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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.
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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); Castañon, 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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    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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    GEICAM Guidelines for the Management of Patients with Breast Cancer During the COVID-19 Pandemic in Spain
    (2020) Algara, M. (Manel); López-Tarruella, S. (Sara); Cruz, J. (Josefina); Jara, C. (Carlos); Montero, Á. (Ángel); García-Sáenz, J.Á. (José Ángel); Gimenez, J. (Julia); Santisteban, M. (Marta); Moreno, F. (Fernando); Chacón, J.I. (José Ignacio); Cruz-Merino, L. (Luis) de la; Martín, M. (Miguel); Rojo-Todo, F. (Federico); Filipovich, E. (Elena); Alés, J.E. (José Enrique); Guerrero-Zotano, A. (Angel)
    Breast cancer (BC) is the most common cancer in women in Spain. During the COVID-19 pandemic caused by the SARSCoV-2 virus, patients with BC still require timely treatment and follow-up; however, hospitals are overwhelmed with infected patients and, if exposed, patients with BC are at higher risk for infection and serious complications if infected. Thus, health care providers need to evaluate each BC treatment and in-hospital visit to minimize pandemic-associated risks while maintaining adequate treatment efficacy. Here we present a set of guidelines regarding available options for BC patient management and treatment by BC subtype in the context of the COVID-19 pandemic. Owing to the lack of evidence about COVID-19 infection, these recommendations are mainly based on expert opinion, medical organizations’ and societies’ recommendations, and some published evidence. We consider this a useful tool to facilitate medical decision making in this health crisis situation we are facing.