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The present proposal argues that it is relevant to design, implement and test more practical strategies to help Interpreting students enhance their second active working language to meet market requirements. Within the framework of a dialogue interpreting B.A. course, a free voluntary reading (FVR) experiment was conducted, based on the extensive literature proving that self-selected reading contributes to improving second language acquisition. The aim was to explore its potential as a Language and Knowledge Enhancement tool in improving native Spanish Interpreting students’ self-perceived fluency in English, and to analyze whether introducing FVR transversally as a horizontal activity in different B.A. in TI courses can help students build more robust active core competences in this foreign language.

Introduction/objectives To describe abemaciclib use in patients with hormone receptor-positive, human epidermal growth factor receptor-negative (HR+/HER2−) metastatic breast cancer (mBC) who participated in the Named Patient Use program (NPU) in Spain. Material and methods This retrospective study was based on medical record review of patients across 20 centers during 2018/2019. Patients were followed up until death, enrolment in a clinical trial, loss of follow-up or study end. Clinical and demographic characteristics, treatment patterns and abemaciclib effectiveness were analyzed; time-to-event and median times were estimated using the Kaplan–Meier (KM) method. Results The study included 69 female patients with mBC (mean age 60.4 ± 12.4 years), 86% of whom had an initial diagnosis of early BC and 20% had an ECOG ≥ 2. Median follow-up was 23 months (range 16–28). Metastases were frequently observed in bone (79%) and visceral tissue (65%), with 47% having metastases in > 2 sites. Median number of treatment lines before abemaciclib was 6 (range 1–10). Abemaciclib monotherapy was received by 72% of patients and combination therapy with endocrine therapy by 28% of patients; 54% of patients required dose adjustments, with a median time to first adjustment of 1.8 months. Abemaciclib was discontinued in 86% of patients after a median of 7.7 months (13.2 months for combination therapy and 7.0 months for monotherapy) mainly due to disease progression (69%). Conclusion These results suggest that abemaciclib is effective, as monotherapy and in combination, for patients with heavily pretreated mBC, consistent with clinical trial results.

Indirect interpreting, known by practitioners as ‘relay’, takes place in contexts where interpreting between two languages is carried out by means of a third, pivot language, thus creating a communicative chain between two interpreters: the one rendering an original speech into a pivot language, and the other rendering the first’s version into a different target language. Relay is used in many multilingual settings to ensure that all interlocutors can use their mother tongue, and the European Union institutions are a prominent example of such settings. Indirect interpreting is thus a reality that many professionals deal with on a daily basis. Despite this, it has not been the subject of much research as yet. This article explores the connections between indirect interpreting and the construct of quality in the ears of the interpreters who regularly give and take relay. The research first involved a focus group comprising six European Union-accredited conference interpreters with Spanish as their mother tongue. A focus group discussion aimed to identify salient issues in the giving and taking of relay across different contexts and meeting formats. The itemised concepts emerging from the discussion were then used to devise a questionnaire to gain further insight into interpreters’ concerns and ideas regarding quality indicators in indirect interpreting. Thirty professionals responded to the questionnaire. The results are analysed with a focus on the lessons that may be insightful for Translation and Interpreting Studies.

Purpose: The present study aimed to determine the prevalence of MUTYH mutations in patients with multiple colonic polyps and to explore the best strategy for diagnosing MUTYH-associated polyposis (MAP) in these patients.Experimental Design: This study included 405 patients with at least 10 colonic polyps each. All cases were genetically tested for the three most frequent MUTYH mutations. Whole-gene analysis was performed in heterozygous patients and in 216 patients lacking the three most frequent mutations. Polyps from 56 patients were analyzed for the KRAS-Gly12Cys and BRAF V600E somatic mutations.Results: Twenty-seven (6.7%) patients were diagnosed with MAP, of which 40.8% showed serrated polyps. The sensitivity of studying only the three common variants was 74.1%. Of 216 patients without any monoallelic mutation in common variants, whole-gene analysis revealed biallelic pathogenic mutation in only one. G396D mutation was associated with serrated lesions and older age at diagnosis. There was a strong association between germinal MUTYH mutation and KRAS Gly12Cys somatic mutation in polyps. BRAF V600E mutation was found in 74% of serrated polyps in MUTYH-negative patients and in none of the polyps of MAP patients.Conclusions: We observed a low frequency of MUTYH mutations among patients with multiple adenomatous and serrated polyps. The MAP phenotype frequently included patients with serrated polyps, especially when G396D mutation was involved. Our results show that somatic molecular markers of polyps can be useful in identifying MAP cases and support the need for the complete MUTYH gene analysis only in patients heterozygous for recurrent variants. Clin Cancer Res; 20(5); 1158–68. ©2014 AACR.

CCR Translation for This Article from Prevalence and Characteristics of MUTYH-Associated Polyposis in Patients with Multiple Adenomatous and Serrated Polyps

Background Palbociclib has gained a central role in the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC). Despite its manageable toxicity profile, venous thromboembolism (VTE) or interstitial lung disease (ILD)/pneumonitis may infrequently occur. Therefore, we provide a comprehensive summary of the safety and tolerability of the combination of endocrine therapy and palbociclib among patients included in the randomized phase 2 PARSIFAL study. Materials and Methods Patients with endocrine-sensitive HR+/HER2- ABC and no prior therapy in an advanced setting (n = 486) were randomly assigned 1:1 to receive fulvestrant–palbociclib (FP) or letrozole–palbociclib (LP). Laboratory tests and the incidence of adverse events (AEs) were recorded at baseline and day 1 of each cycle. Progression-free survival (PFS) was estimated for patients with and without VTE. Results A total of 483 patients were analyzed. Neutropenia, leukopenia, anemia, asthenia, arthralgia, fatigue, and diarrhea were the most frequent AEs in both groups. Febrile neutropenia occurred in 3 (1.2%) patients of the FP group and in 1 (0.4%) patient in the LP group. Six (2.5%; 0.4% grade 3) patients in the FP group and 6 patients (2.5%; 0.4% grade 3) in the LP group experienced ILD/pneumonitis. Pulmonary embolism was reported in 12 (5.0%) patients in the FP group and 6 (2.5%) patients in the LP group. Advanced age at baseline was the only factor significantly associated with an increased risk of pulmonary embolism (P Conclusion The PARSIFAL data confirmed the favorable safety profile of both palbociclib regimens. VTE and ILD/pneumonitis were occasionally reported, and their early detection allowed patients to continue treatment effectively without detriment to efficacy. ClinicalTrials.gov Identifier NCT02491983; https://clinicaltrials.gov/ct2/show/NCT02491983).

Resumen Objetivo Evaluar el uso de la terapia con beneficio cardiovascular en pacientes con DM tipo 2 previo al ingreso en servicios de medicina interna. Metodos Estudio transversal en un dia de los pacientes con DM tipo 2 hospitalizados en servicios de medicina interna. Se recogieron variables demograficas y antropometricas, datos de laboratorio y utilizacion de farmacos antihiperglucemiantes. La variable desenlace fue la proporcion y los determinantes de uso de inhibidores del cotransportador sodio-glucosa 2 (iSGLT2) y de agonistas del receptor del peptido similar al glucagon tipo 1 (AR-GLP1). Resultados Se incluyeron 928 pacientes pertenecientes a 74 hospitales. La edad media fue 78,9 anos (DE: 10,86), un 50% varones. Un total de 557 (60%) presentaba cardiopatia isquemica, 189 (20,4%) enfermedad cerebrovascular, 293 (31,6%) insuficiencia cardiaca, 274 (29,5%) enfermedad renal cronica y 129 (13,9%) enfermedad arterial periferica. Los antihiperglucemiantes utilizados previo al ingreso fueron: sulfonilureas (5.7%), biguanidas (49.1%), inhibidores de la alfa-glucosidasa (0,2%), pioglitazona (0%), iDPP4 (39%), iSGLT2 (5,8%), AR-GLP1 (2,6%) y analogos de insulina basal (24%). La edad mayor de 75 anos fue el factor determinante principal para no utilizar iSGLT2 (OR ajustada 0,28; intervalo de confianza al 95%: 0,10-0,74; p = 0,039) o AR-GLP1 (OR ajustada 0,09; intervalo de confianza al 95%: 0,02-0,46; p = 0,006). Discusion Una gran proporcion de pacientes ancianos con DM tipo 2 de muy alto riesgo cardiovascular no recibe terapia antihiperglucemiante con farmacos de probado beneficio cardiovascular. El tratamiento mas frecuentemente utilizado fue metformina e iDPP4. Existe un margen de mejora en el tratamiento en esta poblacion de muy alto riesgo.

Background: P led to a meaningful improvement in clinical outcomes when used in combination with endocrine therapy for first- or later-line regimen in HR[+]/HER2[-] MBC. Grade 3-4 neutropenia was the most common adverse event (AE) in the P-containing regimens. Although venous thromboembolic events (VTE) have been rarely reported in registrational trials, a systematic review and meta-analysis of randomized controlled trials demonstrated a higher rate of these AEs. Moreover, rare but severe cases of interstitial lung disease (ILD)/pneumonitis have been observed during post-approval use of P. Here, we present a comprehensive toxicity profile of pts included in the PARSIFAL study, with particular emphasis given to AEs of special interest of the overall safety population. Methods: A total of 486 pts with HR[+]/HER2[-] MBC with no prior therapy in the advanced setting and endocrine sensitive criteria (relapse >12 months [mo] after the end of adjuvant endocrine therapy or diagnosed with de novo metastatic disease) were randomly assigned 1:1 to receive P (oral 125 mg/day [d]; 3 weeks on/1 week off) plus either F (intramuscular injection 500 mg/d; d 0, 14, 28, and then every 28 ds) or L (oral 2.5 mg/d). Pts were stratified by visceral involvement and type of disease presentation (de novo/recurrent). Safety assessments included blood analysis and collection of vital signs at screening, d1 of each cycle, and end of treatment/withdrawal. Severity was graded as per the NCI Common Terminology Criteria for Adverse Events v.4.03. Results: The incidence rate of any grade, grade 3-4, and serious AEs was 99.6%, 80.9%, and 29.9%, respectively, in the FP arm, and 99.2%, 78.5%, and 21.1% in the LP arm. Discontinuations due to AEs were 5.4% in the FP arm and 2.1% in the LP arm. Neutropenia, leukopenia, anemia, asthenia, arthralgia, fatigue, and diarrhea were the most frequent AEs in both arms. Febrile neutropenia was reported in 1.2% (3 pts) and 0.4% (1 patient) in the FP and LP arms, respectively. The rate of VTE of any grade was 5.8% (14 pts) in the FP arm and 4.5% (11 pts) in the LP arm (p = 0.531). Among 18 pts who had grade ≥ 3 pulmonary embolism (PE), the incidence reported in the FP and LP arms was 5% (12 pts) vs 2.5% (6 pts), respectively, and many of them (n=16, 88.9%) were unrelated PE. Asymptomatic grade 3 PE was reported in 10 pts of the entire study population on every 3-mo CT scan. Further, in 5 pts PE was detected in the context of progressive disease. Median time from the first dose of study drugs to occurrence of PE was 4.1 mo (range 1.4-32.0 mo) in the FP arm and 7 mo (range 1.8-19.3 mo) in the LP arm. Analysis of baseline characteristics in the whole population revealed that older pts had a significantly increased risk for developing PE (69.5 years [range 47-84 years]; p < 0.01). ECOG performance status, menopausal status, metastatic disease, visceral involvement, number of disease sites, and prior therapies including antithrombotic agents did not significantly increase the risk for developing PE. Grade 3 ILD/pneumonitis was rarely observed in the FP and LP arms (0.8% vs 1.2%, respectively) with no grade 4 AE. Conclusions: First-line treatment with FP and LP for HR[+]/HER2[-] MBC in the PARSIFAL study confirmed the favorable safety profile, with neutropenia representing the most common AE. Although rare, ILD/pneumonitis can be a side effect of P-based regimens. VTE and PE incidence rates were low and consistent with age-specific analyses from PALOMA trials and breast cancer population. Early detection of these AEs may assist in optimizing their management. Citation Format: José Manuel Pérez-García, Antonio Llombart-Cussac, Meritxell Bellet, Florence Dalenc, Miguel J. Gil Gil, Manuel Ruiz Borrego, Joaquín Gavilá, Miguel Sampayo-Cordero, Elena Aguirre, Peter Schmid, Frederik Marmé, Serena Di Cosimo, Joseph Gligorov, Andreas Schneeweiss, Joan Albanell, Pilar Zamora, Duncan Wheatley, Eduardo Martínez-De Dueñas, Vicente Carañana, Kepa Amillano, Andrea Malfettone, Javier Cortés. Palbociclib (P) in combination with fulvestrant (F) or letrozole (L) in endocrine-sensitive patients (pts) with hormone receptor (HR)[+]/HER2[-] metastatic breast cancer (MBC): detailed safety analysis from a multicenter, randomized, open-label, phase II trial (PARSIFAL) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-17.

The development of online interactive resources for interpreter training has been at the centre of the agenda in terms of pedagogical assistance and cooperation both for the European Institutions and for their partner universities. Modern videoconferencing systems and online learning technologies provide an excellent alternative to face-to-face classes, offering solutions to the problem of trainers’ availability and engaging learners in synchronous and asynchronous task-oriented activities. In this context, the European Parliament-funded ERITON project was launched in 2014 with the aim of facilitating the dissemination of best practices and enhancing collaboration between EU and non-EU partner universities in the field of conference interpreter training. Forming the strategic core of this project was the use of innovative training methodologies, such as virtual classes and virtual mock-conferences. This paper presents the pedagogical framework of the VCs and discusses the results of an online survey conducted from 2015 to 2017 among students who actively participated in the virtual classes held within the ERITON project. The aim of the survey was to obtain anonymous feedback on the technical set-up of the VCs and on the helpfulness of this format in terms of skill acquisition and progress. The results show that the new medium was well-received and appreciated by respondents, especially since it gave them the possibility to interact in ways and with people that would otherwise be impossible.

El sector de exportación agropecuario ha sido uno de los que ha hecho posible la sobrevivencia de la economía panameña durante esta pandemia del Covid-19, en los últimos años el aguacate Hass ha experimentado importantes incrementos en su producción nacional. El siguiente artículo de investigación presenta una síntesis del estado de la situación actual con respecto a las estadísticas de producción y exportación proyectada del aguacate Hass. Luego se realizan estimaciones estadísticas con estas cifras oficiales, gremios y entidades del sector privado. Los resultados de este estudio reflejan un aumento promedio en la producción del aguacate Hass desde el año 2014 al 2019, el aumento más significativo en la producción fue en el período 2018/19. La provincia de Chiriquí tiene la mayor producción de aguacate Hass con un 80%, en comparación con las provincias de Coclé y Veraguas. Los resultados de este estudio concluyen que la producción del aguacate Hass, puede convertirse en un factor de ingreso económico para todos los productores de este a nivel nacional, sobre todo en la provincia de Chiriquí.

BACKGROUND & AIMS: Colonoscopy reduces colorectal cancer (CRC) incidence and mortality in Lynch syndrome (LS) carriers. However, a high incidence of postcolonoscopy CRC (PCCRC) has been reported. Colonoscopy is highly dependent on endoscopist skill and is subject to quality variability. We aimed to evaluate the impact of key colonoscopy quality indicators on adenoma detection and prevention of PCCRC in LS. METHODS: We conducted a multicenter study focused on LS carriers without previous CRC undergoing colonoscopy surveillance (n = 893). Incident colorectal neoplasia during surveillance and quality indicators of all colonoscopies were analyzed. We performed an emulated target trial comparing the results from the first and second surveillance colonoscopies to assess the effect of colonoscopy quality indicators on adenoma detection and PCCRC incidence. Risk analyses were conducted using a multivariable logistic regression model. RESULTS: The 10-year cumulative incidence of adenoma and PCCRC was 60.6% (95% CI, 55.5%-65.2%) and 7.9% (95% CI, 5.2%-10.6%), respectively. Adequate bowel preparation (odds ratio [OR], 2.07; 95% CI, 1.06-4.3), complete colonoscopies (20% vs 0%; P = .01), and panchromoendoscopy use (OR, 2.14; 95% CI, 1.15-3.95) were associated with significant improvement in adenoma detection. PCCRC risk was significantly lower when colonoscopies were performed during a time interval of less than every 3 years (OR, 0.35; 95% CI, 0.14-0.97). We observed a consistent but not significant reduction in PCCRC risk for a previous complete examination (OR, 0.16; 95% CI, 0.03-1.28), adequate bowel preparation (OR, 0.64; 95% CI, 0.17-3.24), or previous use of high-definition colonoscopy (OR, 0.37; 95% CI, 0.02-2.33). CONCLUSIONS: Complete colonoscopies with adequate bowel preparation and chromoendoscopy use are associated with improved adenoma detection, while surveillance intervals of less than 3 years are associated with a reduction of PCCRC incidence. In LS, high-quality colonoscopy surveillance is of utmost importance for CRC prevention.

Background The use of PPI among cancer patients (pts) is quite frequent. PAL is an oral, cyclin-dependent kinase 4 and 6 inhibitor recommended to be taken under fed conditions. PAL showed a reduced solubility when gastric pH is >4.5, a level commonly achieved by PPI. Observational, retrospective studies on concomitant PPI with PAL or ribociclib showed a shorter progression-free survival (PFS) among PPI users than nonusers. In the randomized, phase 2 PARSIFAL trial, PAL plus fulvestrant demonstrated no improvement in PFS and overall survival (OS) versus PAL plus letrozole as frontline treatment in HR+/HER2- ABC pts (Llombart-Cussac et al, JAMA Oncol 2021). Here we assessed the impact of PPI on PAL efficacy and safety in pts included in the PARSIFAL study. Methods Pts with endocrine-sensitive HR+/HER2- ABC and no prior therapy in advanced setting were randomly assigned to receive PAL (hard capsule formulation) plus either fulvestrant or letrozole. Pts with ≥1 PPI received over the entire PAL-based regimen were defined as PPI users, or PPI naïve (N-PPI) if no PPI was administered over the whole study treatment. We carried out two analyses considering early PPI users (E-PPI) –composed by pts who were receiving PPI since the PAL-based regimen initiation– and long-term PPI users (LT-PPI) –composed by pts who received PPI over the entire or ≥⅔ of the PAL-based regimen. PPI users defined as neither E-PPI nor LT-PPI were excluded from the analysis to avoid biases due to the PPI limited exposition. PFS, OS, and safety were compared among groups. Landmark analysis at 3, 6, 12, 18, 24, and 30 months (mo) was used for survival estimates conditional on surviving to certain time points and adjust for immortality bias in comparison between N-PPI and PPI users. Analyses were adjusted by stratification factors and patient characteristics. Results Of 486 pts included in the study, 325 (66.9%) were N-PPI. Among 161 (33.1%) PPI users, 64 (13.2%) were E-PPI and 91 (18.7%) were LT-PPI. Omeprazole was the most prescribed PPI in 80.7% (130 of 161) of PPI users. Median exposition to PPI for PPI users, E-PPI, and LT-PPI was 13.6, 15.9, and 19.4 mo, respectively. Compared with N-PPI, E-PPI and LT-PPI were older (median age, 60.5 vs 66.5 vs 67.0 years, respectively; P< 0.001) and had a worse functional status (ECOG PS of 0, 60.0% vs 34.0% vs 43.0%, respectively; P=0.002). Median follow-up for the whole population was 32 mo. Median PFS was 28.7 mo in N-PPI compared with 23.0 mo in E-PPI (HR 1.5; 95%CI 1.1–2.2; P=0.024) and 23.0 mo in LT-PPI (HR 1.4; 95%CI 1.0–1.9; P=0.035). Both PPI groups had poorer median PFS than N-PPI by landmark analysis at 3 and 12 mo. Subgroup analysis showed a consistent trend regardless of endocrine partner. Three-year OS rate was 81.1% in N-PPI compared with 63.5% in E-PPI (HR 2.2; 95%CI 1.3–3.7; P=0.003) and 62.0% in LT-PPI (HR 2.1; 95%CI 1.4–3.4; P=0.001). Both PPI groups had poorer 3-year OS rate than N-PPI by landmark analysis at 3, 6, 12, and 18 mo. Grade ≥3 hematological adverse events (AEs) occurred in 71.7% (233 of 325 pts) of N-PPI compared with 57.8% (37 of 64 pts; P=0.021) of E-PPI and 54.9% (50 of 91 pts; P=0.003) of LT-PPI. Dose reductions and delays due to hematological AEs were reported in 70.8% (230 of 325 pts) of N-PPI compared with 56.3% (36 of 64 pts; P=0.018) of E-PPI and 52.7% (48 of 91 pts; P=0.002) of LT-PPI. At 3 mo, 45.8% (149 of 325 pts) of N-PPI required a dose reduction or delay due to hematological AEs compared with 39.1% (25 of 64 pts; P=0.42) of E-PPI. Conclusions Early and sustained coadministration of PPI with PAL and endocrine therapy were associated with lower efficacy, hematological toxicities, and dose modifications. Despite the post-hoc nature of the study, these findings suggest pharmacokinetic interactions between PPI and PAL capsules. Further confirmatory studies including the tablet formulation of PAL, which is expected to assure its optimal absorption, are needed. Citation Format: Serena Di Cosimo, José Manuel Pérez-García, Meritxell Bellet Ezquerra, Florence Dalenc, Miguel Gil Gil, Manuel Ruiz Borrego, Joaquín Gavilá, Miguel Sampayo-Cordero, Elena Aguirre, Peter Schmid, Frederik Marmé, Joseph Gligorov, Andreas Schneeweiss, Joan Albanell, Pilar Zamora, Duncan Wheatley, Eduardo Martínez De Dueñas, Vicente Carañana, Kepa Amillano, Andrea Malfettone, Javier Cortés, Antonio Llombart-Cussac. PD13-10 Impact of Proton Pump Inhibitors (PPI) on Palbociclib (PAL) Outcomes in Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer (HR+/HER2- ABC): Exploratory Analysis of the PARSIFAL Trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD13-10.

The ability of interpreters to engage in metacognitive activity enabling them to self-assess the changing purpose of their task and subsequent strategies can play a pivotal role in their global attainment levels. This paper argues that developing a high degree of metacognition can be key, not only for the expert’s interpreting performance, but also for trainees’ learning processes, helping them develop a more accurate professional self-concept and better self-regulation techniques. The study, carried out with 199 interpreting trainees, tested a tool to assess self-perceived metacognition levels. The measurement tool was developed on the basis of previous relevant academic contributions to the overlapping fields of Education, Interpreting and Psychology. According to the results of a factor analysis, self-perceived metacognition in interpreting trainees can be defined as a construct made up of four dimensions: self-knowledge perception, consolidation of one’s own set of criteria, development of a macro-strategy, and task-focused flow.

Question Which is the optimal endocrine partner (fulvestrant vs letrozole) for cyclin-dependent kinase 4 and 6 inhibitor palbociclib in previously untreated, endocrine-sensitive, hormone receptor-positive, ERBB2-negative advanced breast cancer? Findings In this randomized, open-label, phase 2 trial, 486 patients were assigned in equal numbers to receive palbociclib plus fulvestrant or letrozole. Median investigator-assessed progression-free survival was 27.9 months for fulvestrant-palbociclib vs 32.8 months for letrozole-palbociclib, a difference that was not statistically significant. Meaning Fulvestrant-palbociclib demonstrated no improvement in progression-free survival over letrozole-palbociclib, confirming letrozole as the preferred palbociclib partner in this patient population. This randomized clinical trial investigates fulvestrant-palbociclib vs letrozole-palbociclib as initial therapy for endocrine-sensitive, hormone receptor-positive, ERBB2-negative breast cancer. IMPORTANCE The cyclin-dependent kinase 4 and 6 inhibitor palbociclib in combination with letrozole has become a standard first-line treatment for patients with endocrine-sensitive, hormone receptor-positive, ERBB2-negative advanced breast cancer. Meanwhile, the antiestrogen fulvestrant was shown to be superior to anastrozole in the absence of cyclin-dependent kinase 4 and 6 inhibition for this patient population. OBJECTIVE To assess whether fulvestrant is superior to letrozole when combined with palbociclib in the first-line scenario. DESIGN, SETTING, AND PARTICIPANTS In this international, randomized, open-label, phase 2 clinical study conducted from July 30, 2015, to January 8, 2018, patients with hormone receptor-positive, ERBB2-negative advanced breast cancer with no prior therapy in the metastatic setting and endocrine-sensitive criteria were recruited from 47 centers in 7 countries. Data were analyzed from February 11 to May 15, 2020. INTERVENTIONS Patients were randomly assigned (1:1 ratio) to receive palbociclib with either fulvestrant or letrozole. Stratification factors were type of disease presentation (de novo vs recurrent) and the presence of visceral involvement (yes vs no). MAIN OUTCOMES AND MEASURES The primary end point was investigator-assessed progression-free survival determined by Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS A total of 486 women (median age, 63 years [range, 25-90 years]; 3 Asian women [0.6%]; 4 Black women [0.8%]; 461 White women [94.9%]; 18 women of unknown race [3.7%]) were randomized (243 to fulvestrant-palbociclib and 243 to letrozole-palbociclib). Median investigator-assessed progression-free survival was 27.9 months (95% CI, 24.2-33.1 months) in the fulvestrant-palbociclib group vs 32.8 months (95% CI, 25.8-35.9 months) in the letrozole-palbociclib group (hazard ratio, 1.13; 95% CI, 0.89-1.45; P = .32). This result was consistent across the stratification factors. No significant differences were observed in objective response rate (46.5% vs 50.2%) and 3-year overall survival rate (79.4% vs 77.1%) for fulvestrant-palbociclib and letrozole-palbociclib, respectively. Grade 3-4 adverse events were comparable among treatment groups, and no new safety signals were identified. No treatment-related deaths were reported. CONCLUSIONS AND RELEVANCE Although fulvestrant-palbociclib demonstrated significant antitumor activity, this randomized clinical trial failed to identify an improvement in progression-free survival with this regimen over letrozole-palbociclib in patients with endocrine-sensitive, hormone receptor-positive, ERBB2-negative advanced breast cancer.

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 (HR+/ 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 HR+/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 = 13) and 46.2% (n = 101), respectively. The median real world progression-free survival (rwPFS) was 6.0 months (95% CI 5.7-7.0) and the median overall survival was 19.0 months (95% CI 16.4-21.7). 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, This study was sponsored by Biomedical Research Foundation of the Hospital Clinico San Carlos (Madrid, Spain). The study was funded by an investigator sponsored research grant (WI236789) from Pfizer.

The primary aim of NSABP FB-7 was to determine the pathologic complete response (pCR) rate in locally advanced HER2-positive (HER2+) breast cancer patients treated with neoadjuvant trastuzumab or neratinib or the combination and weekly paclitaxel followed by standard doxorubicin plus cyclophosphamide. The secondary aims include biomarker analyses. pCR was tested for association with treatment, gene expression, and a single nucleotide polymorphism (SNP) in the Fc fragment of the IgG receptor IIIa-158V/F (FCGR3A). Pre-treatment biopsies and residual tumors were also compared to identify molecular changes. The numerical pCR rate in the trastuzumab plus neratinib arm (50% [95%CI 34–66%]) was greater than that for single-targeted therapies with trastuzumab (38% [95%CI 24–54]) or neratinib (33% [95%CI 20–50]) in the overall cohort but was not statistically significant. Hormone receptor-negative (HR−) tumors had a higher pCR rate than HR+ tumors in all three treatment arms, with the highest pCR rate in the combination arm. Diarrhea was the most frequent adverse event and occurred in virtually all patients who received neratinib-based therapy. Grade 3 diarrhea was reported in 31% of patients; there were no grade 4 events. Our 8-gene signature, previously validated for trastuzumab benefit in two different clinical trials in the adjuvant setting, was correlated with pCR across all arms of NSABP FB-7. Specifically, patients predicted to receive no trastuzumab benefit had a significantly lower pCR rate than did patients predicted to receive the most benefit (P = 0.03). FCGR genotyping showed that patients who were homozygous for the Fc low-binding phenylalanine (F) allele for FCGR3A-158V/F were less likely to achieve pCR. Combining trastuzumab plus neratinib with paclitaxel increased the absolute pCR rate in the overall cohort and in HR− patients. The 8-gene signature, which is validated for predicting trastuzumab benefit in the adjuvant setting, was associated with pCR in the neoadjuvant setting, but remains to be validated as a predictive marker in a larger neoadjuvant clinical trial. HR status, and the FCGR3A-158V/F genotype, also warrant further investigation to identify HER2+ patients who may benefit from additional anti-HER2 therapies beyond trastuzumab. All of these markers will require further validation in the neoadjuvant setting. ClinicalTrials.gov, NCT01008150. Retrospectively registered on October 5, 2010.

Recurrence of Clostridium difficile infection (CDI) has major consequences for both patients and the health system. The ability to predict which patients are at increased risk of recurrent CDI makes it possible to select candidates for treatment with new drugs and therapies (including fecal microbiota transplantation) that have proven to reduce the incidence of recurrence of CDI. Our objective was to develop a clinical prediction tool, the GEIH-CDI score, to determine the risk of recurrence of CDI. Predictors of recurrence of CDI were investigated using logistic regression in a prospective cohort of 274 patients diagnosed with CDI. The model was calibrated using the Hosmer-Lemeshow test. The tool comprises four factors: age (70-79 years and >= 80 years), history of CDI during the previous year, direct detection of toxin in stool, and persistence of diarrhea on the fifth day of treatment. The functioning of the GEIH-CDI score was validated in a prospective cohort of 183 patients. The area under the ROC curve was 0.72 (0.65-0.79). Application of the tool makes it possible to select patients at high risk (> 50%) of recurrence and patients at low risk (< 10%) of recurrence. GEIH-CDI score may be useful for clinicians treating patients with CDI. (C) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

This abstract was withdrawn by the authors.

Background: Adherence to treatment is one of the mainstays of non-communicable diseases adequate control. Non – adherence can affect several aspects to both the patient and the health system. For this reason, it is important to have intervention strategies available to prevent detachment and improve adherence to treatment. The objective of this study is to evaluate the effectiveness of the educational strategy compared with the social and family support for the improvement of adherence in patients with chronic noncommunicable diseases. Methods: A quasi-experimental study was conducted in 159 participants with diagnosis of arterial hypertension or/and diabetes mellitus type 2 plus polypharmacy. Participants were divided in two groups and strategies: Group A: educational (n = 79) and Group B social/family support (n = 80), follow up three months for each group. For group "A", informative group workshops were assigned; while for group "B" therapeutic agreements were established. Adherence to treatment pre- and post-intervention were evaluated using the four item Morisky Green Levine scale of public domain. At the end of the intervention period, an intra and intergroup analysis were performed and a Z test for difference in proportions was applied; the RR was used as a measure of association, and Chi2 as a measure of significance. Results: A total of 152 patients complete the intervention. In group A, pre-intervention non-adherence was 58.2%, post-intervention of 45.3% and final reduction of the failure was 12.9% (p 0.05). Statistically significant difference was obtained between the decrease in the failure reached after the application of the educational strategy compared to social / family support strategy (p = 0.001). Conclusions: Educational strategy is more effective than social/family support strategy, to reduce the failure of therapeutic adherence. There was not association of sociodemographic factors and adherence to treatment.

The purpose of the MERIBEL trial was to evaluate the efficacy and safety of eribulin monotherapy as first-line therapy for patients with aggressive taxane-pretreated HER2-negative metastatic breast cancer with a short disease-free interval. The median time to progression was 4.1 months, and the clinical benefit rate was 26.4%. These results confirm that eribulin represents an effective therapeutic option for this poor-prognosis population. Background: Eribulin has efficacy in patients with progression after >= 1 chemotherapeutic regimen for metastatic breast cancer (MBC). A short disease-free interval (DFI) and previous use of taxanes in the neoadjuvant or adjuvant setting have been associated with worse outcomes for patients receiving first-line chemotherapy for HER2-negative MBC. The aim of the present trial was to evaluate the efficacy and safety of eribulin as first-line therapy for patients with HER2-negative MBC with these poor prognostic factors. Patients and Methods: Eribulin monotherapy was administered until disease progression or unacceptable toxicity. The principal selection criteria were HER2 negativity without previous chemotherapy for MBC, the previous use of taxanes for early-stage breast cancer, and a DFI of < 36 months (subsequently amended to 48 months). The primary endpoint was the investigator-assessed time to progression. The secondary endpoints included overall survival, progression-free survival, objective response rate, clinical benefit rate, duration of response, and toxicity profile. A total of 53 patients were enrolled and received >= 1 dose of eribulin. Results: The median patient age was 47 years (range, 23-82.8 years). The median DFI was 15.7 months (range, 0.1-46.4 months). The median investigator-assessed time to progression was 4.1 months (range, 0.2-27.8 months; 95% confidence interval, 3.2-6.2 months). The objective response and clinical benefit rate was 20.8% and 26.4%, respectively. All-grade and grade 3/4 adverse events developed in 96.2% and 69.8% of patients, respectively. The most common treatment-related adverse events were neutropenia, leukopenia, alopecia, nausea, and anemia. Conclusion: Eribulin is effective and safe as first-line therapy for aggressive taxane-pretreated HER2-negative MBC. (C) 2018 Elsevier Inc. All rights reserved.

Background: International consensus stresses the preference for endocrine therapies (ET) for the ER[+]/HER2[-] ABC population. However, in real-world, chemotherapy (CT) is an extended practice long before exhausting endocrine options (Swallow E, Curr Med Res Opin. 2014). There is little knowledge on the prognostic factors that drives OS among the ER[+]/HER2[-] population at the time of first line CT for ABC. Methods: The Athena trial assessed safety of different first-line CT & bevacizumab regimens in 2.264 patients (pts) treated between 2006 and 2009 over 34 countries. A total of 1.492 ER/PgR[+]/HER2[-] pts were identified, as 585 TNBC pts (control arm). We adapted the ESMO 2012 guidelines of endocrine resistance to the data collected, considering 5 years the median duration of (neo)adjuvant ET. Endocrine resistance status (ERS) at the time of inclusion was measured by: (1) Progression on ET for Early stage (EEP) [on or within the first year of], and (2) Prior ET for ABC (AEP), whatever the duration or number of endocrine lines. Three ES were pre-defined: Low sensitive (LS): patients with both EEP and AEP criteria; moderately sensitive (MS): either EEP or AEP criteria, and Highly sensitive (HS): neither EEP nor AEP criteria. Other prognostic factors (PF) identified in a prior analysis (Llombart-Cussac A, Breast 2014) were incorporated in a multivariate Cox proportional-hazard model. Results: Median age was 53 years (range 22-93); 5.2% ECOG ≥2 and 28.9% with prior analgesic treatment. ER/PgR positivity were 94.4%/76% respectively. Patients were previously exposed to anthracycline (53.5%) and taxanes (21.4%) for early stage BC. Prior endocrine therapy in (neo)adjuvant and metastatic settings were (65.3%) and (31.8%), respectively. Pts de novo metastatic represented 19.3%, and the median DFI in pts progressing from an early stage was 43.2 mo. Liver involvement was observed in 40.3% of pts and 20.5% presented ≥3 organs involved. The ES for the population was HS: 492 pts (33%), MS: 755 pts (50.6%) and LS: 245 pts (16.4%). After median follow-up of 22.6 months (range: 0.1 to 43.6) and 752 OS events (50.4% of pts), median OS for HS, MS, LS and TNBC groups were >40 mo. (median not achieved), 26.3 (95%CI: 24.5–28.4), 20.1 (95%CI: 17.8–23.9) and 18.3 (95%CI: 16.3–19.7) respectively. 3-years OS survival rates for HS, MS, LS and TNBC were 53.5%, 34.8%, 23.9% and 26.6%, respectively. Multivariate-adjusted hazard ratios of OS for (HS vs LS) and (HS vs MS) were 2 (IC95%: 1.6–2.5) and 1.5 (IC95%: 1.2–1.8). The other PF related with OS were: ECOG≥2 or analgesics or corticosteroids 1.6 (IC95%: 1.4–1.8); liver mets or>2 involved organs 1.4 (IC95%: 1.2–1.6) and adjuvant anthracyline and/or taxane 1.2 (IC95%: 1.1–1.4). Conclusions: Nearly to 40% of ER[+]/HER2[-] ABC pts confronted to first line CT were precluded as highly sensitive to ET, achieving a median OS that doubles the less sensitive groups. Confirmatory studies with post-treatment information may be important to link this benefit to ET. However Endocrine Status may be useful to appropriately characterize or select patients in future first-line CT studies for HER2[-] pts. Citation Format: Llombart A, de la Haba-Rodríguez JR, Gligorov J, Aguirre E, Sampayo M, Cortes J. Prognostic relevance of prior endocrine treatments in overall survival (OS) at the time of first line chemotherapy in ER[+]/HER2[-] advanced breast cancer (ABC) patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-13-09.

Objective: Endometrial cancer is the second most frequent neoplasm in women with Lynch syndrome (LS). We sought to assess whether analyzing women with endometrial cancer would identify families with LS not identified with current clinical criteria. Methods: We included women diagnosed with endometrial cancer younger than 50 years and also older if they had a family cancer history associated with LS. In blood samples obtained, we analyzed mutations in mismatch repair (MMR) genes, as well as protein expression by immunohistochemistry and microsatellite instability (MSI) in tumour tissue. Results: A total of 103 patients were enrolled. We detected 14 pathogenic mutations and 4 genetic variants of unknown clinical significance in MMR genes. We found MSI in 41.66% of the women with a pathogenic mutation. In this group, 76.92% showed loss of at least one MMR protein. Women with mutations were younger at diagnosis, but all of them had a family history compatible with LS. Conclusions: Analysis of the MMR genes, in particular MSH6, seems to be appropriate in women with endometrial cancer and a family history of tumours associated with LS.

1007 Background: The CDK4/6 inhibitor palbociclib (P) in combination with letrozole (L) has become a standard first-line treatment for patients (pts) with luminal metastatic breast cancer (MBC) (PALOMA-1 & 2 trials). Meanwhile, the anti-estrogen fulvestrant (F) showed to be superior to anastrozole in the same population (FALCON trial). We aimed to identify the best endocrine agent to combine with P in this first-line scenario. Methods: A total of 486 pts with ER[+]/HER2[-] MBC with no prior therapy in the advanced setting and endocrine sensitive criteria (relapse > 12 months [mo] after the end of adjuvant endocrine therapy or diagnosed with “de novo” metastatic disease) were randomly assigned (1:1 ratio) to receive P (oral 125 mg/day [d]; 3 wks on/1 wk off) plus F 500 mg/d (I.M Days 0, 14, 28, and then every 28 d) or PL (oral 2.5 mg/d). Pts were stratified by visceral involvement and type of disease presentation (“de novo”/recurrent). Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), and safety. 254 events were needed with 80% power to detect a hazard ratio (HR) ≤0.7 in favor of PF (2-sided α = 0.05). Results: By March 9th, 2020, 256 PFS events occurred. Pts characteristics were well balanced. Median age was 62 years (range: 25–90), 56.6% were ECOG 0, 40.7% had “de novo” metastatic disease, 48% had visceral disease, and 43.6% with ≥3 organ sites involved. At median follow-up of 32 mo, median PFS was 27.9 mo (95% confidence interval [CI], 24.2-33.1) with PF and 32.8 mo (95% CI, 25.8-35.9) with PL (HR: 1.1; 95% CI, 0.9-1.5; P = 0.321). No differences were observed for pts with or without visceral involvement (HR: 1.3 and HR: 0.97 respectively, interaction P = 0.275), and for “de novo” or recurrent metastatic disease (HR: 1.1 and HR: 1.1 respectively, P = 0.979). The 4-year OS rate was 67.6% in PF and 67.5% in PL arm (HR: 1; 95% CI, 0.7-1.5; P = 0.986). No differences were observed in ORR or CBR between arms. Grade ≥3 adverse events were similar in both arms, being neutropenia and leukopenia the most frequent. No treatment-related deaths were reported. Conclusion: This study was not able to identify an improvement in PFS for PF over PL in patients with endocrine-sensitive ER[+]/HER2[-] MBC. As both arms demonstrated comparable 4 years-OS, PF is a reasonable alternative to PL in this setting. Clinical trial information: NCT02491983 .

Lynch syndrome (LS) is an autosomal dominant condition characterized by an increased risk of hereditary colorectal, endometrial, ovarian, pancreatic, urinary tract, and gastric cancer. It is estimated that around 5% of all endometrial cancer (EC) cases are due to an inherited predisposition, of which LS might be the most frequent. The lifetime risk of developing EC in women with LS ranges between 40% and 71% depending on the type of mutation. In many cases, this risk may even exceed their risk of developing colon cancer. Moreover, in 60% of these women, EC will be the first primary malignancy diagnosed and the sentinel diagnosis of the syndrome. Therefore, it is essential to identify which women with EC have LS in order to allow implementation of individualized screening and preventive strategies.

Improved understanding of risk of recurrence (ROR) is needed to reduce cases of recurrence and more effectively treat breast cancer patients. The purpose of this study was to examine how a gene-expression profile (GEP), identified by Prosigna, influences physician adjuvant treatment selection for early breast cancer (EBC) and the effects of this influence on optimizing adjuvant treatment recommendations in clinical practice. A prospective, observational, multicenter study was carried out in 15 hospitals across Spain. Participating medical oncologists completed pre-assessment, post-assessment, and follow-up questionnaires recording their treatment recommendations and confidence in these recommendations, before and after knowing the patient’s ROR. Patients completed questionnaires on decision-making, anxiety, and health status. Between June 2013 and January 2014, 217 patients enrolled and a final 200 were included in the study. Patients were postmenopausal, estrogen receptor positive, human epidermal growth hormone factor negative, and node negative with either stage 1 or stage 2 tumors. After receiving the GEP results, treatment recommendations were changed for 40 patients (20%). The confidence of medical oncologists in their treatment recommendations increased in 41.6% and decreased in 6.5% of total cases. Patients reported lower anxiety after physicians made treatment recommendations based on the GEP results (p Though this study does not include evaluation of the impact of GEP on long-term outcomes, it was found that GEP results influenced the treatment decisions of medical oncologists and their confidence in adjuvant therapy selection. Patients’ anxiety about the selected adjuvant therapy decreased with use of the GEP.

Purpose: The present study aimed to determine the prevalence of MUTYH mutations in patients with multiple colonic polyps and to explore the best strategy for diagnosing MUTYH-associated polyposis (MAP) in these patients. Experimental Design: This study included 405 patients with at least 10 colonic polyps each. All cases were genetically tested for the three most frequent MUTYH mutations. Whole-gene analysis was performed in heterozygous patients and in 216 patients lacking the three most frequent mutations. Polyps from 56 patients were analyzed for the KRAS-Gly12Cys and BRAF V600E somatic mutations. Results: Twenty-seven (6.7%) patients were diagnosed with MAP, of which 40.8% showed serrated polyps. The sensitivity of studying only the three common variants was 74.1%. Of 216 patients without any monoallelic mutation in common variants, whole-gene analysis revealed biallelic pathogenic mutation in only one. G396D mutation was associated with serrated lesions and older age at diagnosis. There was a strong association between germinal MUTYH mutation and KRAS Gly12Cys somatic mutation in polyps. BRAF V600E mutation was found in 74% of serrated polyps in MUTYH-negative patients and in none of the polyps of MAP patients. Conclusions: We observed a low frequency of MUTYH mutations among patients with multiple adenomatous and serrated polyps. The MAP phenotype frequently included patients with serrated polyps, especially when G396D mutation was involved. Our results show that somatic molecular markers of polyps can be useful in identifying MAP cases and support the need for the complete MUTYH gene analysis only in patients heterozygous for recurrent variants. Clin Cancer Res; 20(5); 1158–68. ©2014 AACR.