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Breast cancer; Predictive markers; Translational research Cáncer de mama; Maradores predictivos; Investigación traslacional Càncer de mama; Marcadors predictius; Recerca translacional Eribulin prolongs overall survival in patients with pre-treated advanced breast cancer. However, no biomarker exists to prospectively select patients who will benefit the most from this drug. SOLTI-1007-NeoEribulin is a phase II, open-label, two-cohort, exploratory pharmacogenomic study in patients with clinical stage I–II HER2-negative breast cancer receiving neoadjuvant eribulin monotherapy treatment. Primary objective was to explore the association of baseline tumor gene expression with pathological complete response in the breast (pCRB) at surgery. Key secondary objectives were pCRB rates in all patients and according to HR status, gene expression changes during treatment and safety. One-hundred one hormonal receptor-positive (HR + ) and seventy-three triple-negative breast cancer (TNBC) patients were recruited. The pCRB rates were 6.4% in all patients, 4.9% in HR + disease and 8.2% in TNBC. The TNBC cohort was interrupted due to a progression disease rate of 30.1%. The pCRB rates differed according to intrinsic subtypes: 28.6% in HER2-enriched, 11.1% in Normal-like, 7.9% in Luminal B, 5.9% in Basal-like and 0% in Luminal A (HER2-enriched vs. others odds ratio = 7.05, 95% CI 1.80–42.14; p-value = 0.032). Intrinsic subtype changes at surgery occurred in 33.3% of cases, mostly (49.0%) Luminal B converting to Luminal A or Basal-like converting to Normal-like. Baseline tumor-infiltrating lymphocytes (TILs) were significantly associated with pCR. Eribulin showed a good safety profile with a low response and pCRB rates. Patients with HER2-negative disease with a HER2-enriched profile may benefit the most from eribulin. In addition, significant biological activity of eribulin is observed in Luminal B and Basal-like subtypes.

El cáncer de vesícula biliar que se presenta como una colecistitis aguda asociada a hemocolecisto y hemobilia es muy infrecuente. Hasta la fecha hay pocos casos informados en la literatura. Presentamos un caso de carcinoma de vesícula biliar diagnosticado tras colecistectomía de urgencia, realizada por hemobilia y colecistitis aguda por hemocolecisto.

© 2021 García-Estévez, Cortés, Pérez, Calvo, Gallegos and Moreno-Bueno., Breast cancer is the most common tumor in women worldwide, and an increasing public health concern. Knowledge of both protective and negative risk factors is essential for a better understanding of this heterogenous disease. We undertook a review of the recent literature and evaluated the relationship between obesity mediators and breast cancer development depending on menopausal status. Excess weight is now pandemic and has replaced tobacco as the main lifestyle-related risk factor for premature death. Although the prevalence of obesity/overweight has increased globally over the last 50 years, the potential harm attributable to excess fat has generally been underestimated. The relationship between overweight/obesity, breast cancer and overall risk appears to be highly dependent on menopausal status. Thus, obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women. We evaluate the role of different clinical factors potentially involved in this seemingly contradictory relationship, including estrogen, mammogram density, adipokines, insulin-signaling pathway activation, and inflammatory status. A key focus of this review is to better understand the impact of body mass index and menopausal status on these clinical factors and, hence, provide some clarity into the inter-relationships involved in this controversial issue.

This paper presents a novel design of a wideband circular polarization 2 × 2 microstrip antenna array working at Ka-band frequencies, from 27.5 to 31 GHz. This module is highly integrable with new silicon beamformer chips, creating a unit cell that can be part of a large electronically steerable antenna for compact, ultra-low-profile, Satcom-on-the-move (SOTM) platforms. A multi-layer structure fabricated in standard printed circuit board (PCB) technology with high-yield substrates has been used. The radiating elements consist of double-stacked circular patches housed in a cavity and fed by H-shaped aperture coupling. It achieves a bandwidth of 16.5 % with a wide beam-width of 95° in the desired band, which is necessary for wide scanning angles in a large phased array. In the 2 × 2 unit cell, the antenna elements are distributed by means of a sequential rotation technique where the separation between two of them is 5.3 mm in the XY-plane. Broadside beam-widths ranging from 53.4° at 27.5 GHz to 42.1° at 31 GHz are achieved, with boresight directivities from 10.7 to 12.9 dBi, respectively, in both the RHCP and LHCP polarization. Moreover, mutual coupling levels below −20 dB and an axial ratio less than 3 dB in the whole band guarantee a good circular polarization purity.

Patients with metastatic triple-negative breast cancer have a poor prognosis. Sacituzumab govitecan is an antibody-drug conjugate composed of an antibody targeting the human trophoblast cell-surface antigen 2 (Trop-2), which is expressed in the majority of breast cancers, coupled to SN-38 (topoisomerase I inhibitor) through a proprietary hydrolyzable linker.In this randomized, phase 3 trial, we evaluated sacituzumab govitecan as compared with single-agent chemotherapy of the physician's choice (eribulin, vinorelbine, capecitabine, or gemcitabine) in patients with relapsed or refractory metastatic triple-negative breast cancer. The primary end point was progression-free survival (as determined by blinded independent central review) among patients without brain metastases.A total of 468 patients without brain metastases were randomly assigned to receive sacituzumab govitecan (235 patients) or chemotherapy (233 patients). The median age was 54 years; all the patients had previous use of taxanes. The median progression-free survival was 5.6 months (95% confidence interval [CI], 4.3 to 6.3; 166 events) with sacituzumab govitecan and 1.7 months (95% CI, 1.5 to 2.6; 150 events) with chemotherapy (hazard ratio for disease progression or death, 0.41; 95% CI, 0.32 to 0.52; P0.001). The median overall survival was 12.1 months (95% CI, 10.7 to 14.0) with sacituzumab govitecan and 6.7 months (95% CI, 5.8 to 7.7) with chemotherapy (hazard ratio for death, 0.48; 95% CI, 0.38 to 0.59; P0.001). The percentage of patients with an objective response was 35% with sacituzumab govitecan and 5% with chemotherapy. The incidences of key treatment-related adverse events of grade 3 or higher were neutropenia (51% with sacituzumab govitecan and 33% with chemotherapy), leukopenia (10% and 5%), diarrhea (10% and1%), anemia (8% and 5%), and febrile neutropenia (6% and 2%). There were three deaths owing to adverse events in each group; no deaths were considered to be related to sacituzumab govitecan treatment.Progression-free and overall survival were significantly longer with sacituzumab govitecan than with single-agent chemotherapy among patients with metastatic triple-negative breast cancer. Myelosuppression and diarrhea were more frequent with sacituzumab govitecan. (Funded by Immunomedics; ASCENT ClinicalTrials.gov number, NCT02574455; EudraCT number, 2017-003019-21.).

Simple Summary Metastasis is the last stage in the development of cancer and usually results in mortality. Cutaneous metastases (CMs) account for 2% of all skin malignancies. Nearly 70% of CMs in women originate from breast cancer (BC). Since CM is usually associated with poor prognosis, the development of management strategies for these patients remains an important clinical challenge. Identifying molecular markers in primary BC that predict CMs and determining the molecular differences between primary tumors and their metastases is of great interest for designing new therapeutic approaches. Abstract Cutaneous metastases (CMs) account for 2% of all skin malignancies, and nearly 70% of CMs in women originate from breast cancer (BC). CMs are usually associated with poor prognosis, are difficult to treat, and can pose diagnostic problems, such as in histopathological diagnosis when occurring long after development of the primary tumor. In addition, the molecular differences between the primary tumors and their CMs, and between CMs and metastases in other organs, are not well defined. Here, we review the main clinical, pathological, and molecular characteristics of breast cancer CMs. Identifying molecular markers in primary BC that predict CM and can be used to determine the molecular differences between primary tumors and their metastases is of great interest for the design of new therapeutic approaches.

Estudi no aleatoritzat; Malaltia rara; Revisió sistemàtica Estudio no aleatorizado; Enfermedad rara; Revisión sistemática Nonrandomized study; Rare disease; Systematic review Nonrandomized studies are usually excluded from systematic reviews. This could lead to loss of a considerable amount of information on rare diseases. In this article, we explore the impact of excluding nonrandomized studies on the generalizability of meta-analyses results on mucopolysaccharidosis (MPS) disease. A comprehensive search of systematic reviews on MPS patients up to May 2020 was carried out (CRD42020191217). The primary endpoint was the rate of patients excluded from systematic reviews if only randomized studies were considered. Secondary outcomes included the differences in patient and study characteristics between randomized and nonrandomized studies, the methods used to combine data from studies with different designs, and the number of patients excluded from systematic reviews if case reports were not considered. More than 50% of the patients analyzed have been recruited in nonrandomized studies. Patient characteristics, duration of follow-up, and the clinical outcomes evaluated differ between the randomized and nonrandomized studies. There are feasible strategies to combine the data from different randomized and nonrandomized designs. The analyses suggest the relevance of including case reports in the systematic reviews, since the smaller the number of patients in the reference population, the larger the selection bias associated to excluding case reports. Our results recommend including nonrandomized studies in the systematic reviews of MPS to increase the representativeness of the results and to avoid a selection bias. The recommendations obtained from this study should be considered when conducting systematic reviews on rare diseases.

Introduction/Background Real-life studies inform on the ‘effectiveness’ of a treatment what is intended to do in routine circumstances. The aim of this study is to evaluate the efficacy of Papilocare® - a multi-ingredient Coriolus versicolor-based vaginal gel- on repairing high-risk (HR) HPV-dependent low-degree cervical lesions and HR-HPV clearance in real-life practice. Methodology Observational, multicenter, prospective, one-cohort study (PAPILOBS study ClinicalTrial.gov: NCT04199260). Currently recruiting 300 vaccinated or not HPV-positive women aged > 25y with Pap smear of ASCUS or LSIL and concordant colposcopy during routine clinical visits in Spain. Patients are treated with Papilocare® 1 cannula/day for 21 days the first month + 1 cannula/alternate days for 5 months. After this 6-month period, patients with altered cytology and/or HPV persistency are treated for a 6-month extension treatment period with the same dosage. Interim analysis of HR-HPV patients with normal Pap smear and concordant colposcopy image (primary endpoint) and patient with HR-HPV cleared (patients with total clearance or partial clearance together with negative Pap smear and normal colposcopy) at 6/12 months is presented. The study was approved by the ethical committee of Public University Hospital of Puerta de Hierro (Madrid). Informed consent was signed by all patients. Results At 6 months, data of 148 and 146 patients for Pap smear/colposcopy and HR-HPV presence, respectively, were available. 67.6% of patients (100/148) had negative Pap smear and concordant colposcopy. HR-HPV clearance was observed in 58.9% of patients (86/146). Data of 46 and 44 patients included in the 6-month extension treatment period for Pap smear/colposcopy and HR-HPV presence, respectively, were available. At 12 months, 78.3% (36/46) of patients had negative Pap smear and concordant colposcopy and HR-HPV clearance was observed in 70.5% (31/44). Considering all study period, 77% (114/148) and 72.6% (106/146) of patients repaired HR-HPV-dependent cervical lesions and cleared HR-HPV, respectively. Conclusion In this interim analysis, repairing of HR-HPV-dependent low-degree cervical lesions and clearing HR-HPV, in real life conditions, was achieved after 6-month treatment with Papilocare® (or extending it up to 12-months if needed) in 3 out of 4 patients. These findings need to be confirmed upon study completion. Disclosures Funding: Procare Health Disclosure: J.Cortes: Advisory/Consulting Role and Speaker at Procare Health. Y. Gaslain: CEO of Procare Health. All other authors have declared no conflicts of interest.

Introduction/Background To evaluate the consistency of the efficacy of a non-hormonal multi-ingredient Coriolus versicolor-based vaginal gel, Papilocare®, on HPV clearance in patients infected by high-risk HPV (HR-HPV) in several studies. Methodology Results at 6 months from independent observational non-comparative studies carried out in three different public centers and in a one private center were compared to results from both a randomized, open, parallel and controlled clinical trial comparing the Papilocare® vs wait and see approach (The Paloma RCT) and a observational, multicenter, prospective, one-cohort study (Papilobs real-life study). Two prospective (Vigo and Bari studies) and two retrospective studies (Coruna and Hospitalet studies) have been performed. Vigo study: HPV clearance of 25 patients infected by HPV 16 and/or 18 was evaluated as a secondary endpoint. Bari study: HPV clearance of 98 HR-HPV patients was evaluated as primary endpoint. Coruna study: 57 medical records of patients with HR-HPV were analyzed. HPV clearance was evaluated as primary endpoint. Hospitalet study: Data of 91 HR-HPV patients were evaluated. Primary endpoint: composite efficacy variable (percentage of patients with normal cytology and/or HPV clearance). Papilobs study: Interim data of 148 HR-HPV patients is presented. HR-HPV clearance was evaluated as secondary endpoint. Paloma RCT: 66 HR-HPV patients were evaluated. Percentage of patients with HR-HPV clearance was assessed as a secondary endpoint. Results After the 6-month treatment period, 48% and 57% of patients cleared HPV 16–18 and HR-HPV in Vigo and Bari studies, respectively. A reduction of 58% was observed in number of HR-HPV patients (Coruna) and 72.5% of patients negativized cytology and/or cleared HR-HPV (Hospitalet) (p≤0.0001 vs baseline for all results, Chi-square). In the Paloma RCT, HR-HPV clearance was observed in 63% of patients treated with Papilocare® vs 40% in the control group. Similar rate of 59% HR-HPV clearance was observed in the interim analysis of the Papilobs study. Conclusion Papilocare® has shown significant and consistent rates of HR-HPV clearance ranging from 50% to 70% in the 6 different studies. This high consistently rate of HR-HPV clearance should be further confirmed in ongoing studies. Disclosures Funding: Procare Health. Disclosures: J.Cortes, S.Palacios, D. Dexeus, L. Serrano: Advisory/Consulting Role and Speakers at Procare Health. Y.Gaslain: CEO of Procare Health. All other authors have declared no conflicts of interest.

Càncer de mama; Diagnòstic; Sèrum Cáncer de mama; Diagnóstico; Suero Breast cancer; Diagnosis; Serum Breast cancer is the cancer with the most incidence and mortality in women. microRNAs are emerging as novel prognosis/diagnostic tools. Our aim was to identify a serum microRNA signature useful to predict cancer development. We focused on studying the expression levels of 30 microRNAs in the serum of 96 breast cancer patients vs. 92 control individuals. Bioinformatic studies provide a microRNA signature, designated as a predictor, based on the expression levels of five microRNAs. Then, we tested the predictor in a group of 60 randomly chosen women. Lastly, a proteomic study unveiled the overexpression and downregulation of proteins differently expressed in the serum of breast cancer patients vs. that of control individuals. Twenty-six microRNAs differentiate cancer tissue from healthy tissue, and 16 microRNAs differentiate the serum of cancer patients from that of the control group. The tissue expression of miR-99a, miR-497, miR-362, and miR-1274, and the serum levels of miR-141 correlated with patient survival. Moreover, the predictor consisting of miR-125b, miR-29c, miR-16, miR-1260, and miR-451 was able to differentiate breast cancer patients from controls. The predictor was validated in 20 new cases of breast cancer patients and tested in 60 volunteer women, assigning 11 out of 60 women to the cancer group. An association of low levels of miR-16 with a high content of CD44 protein in serum was found. Circulating microRNAs in serum can represent biomarkers for cancer prediction. Their clinical relevance and the potential use of the predictor here described are discussed. This work was supported by ISCIII (Instituto de Salud Carlos III) Ref. FIS PI15/01262, co-financed by the European Regional Development Fund (ERDF) and AECC Project GEC Ref. GC16173720CARR (ML). AF, YG-M, and CM were granted with P-FIS, VHIR, and iP-FIS fellowships, respectively.

COVID-19; Atenció al càncer; Orientació del pacient COVID-19; Cuidado del cáncer; Orientación al paciente COVID-19; Cancer care; Patient guidance A Commentary on: SARS-CoV-2 Transmission in Patients With Cancer at a Tertiary Care Hospital in Wuhan, China. By Yu, J., Ouyang, W., Chua, M. L. K., and Xie, C. (2020). JAMA Oncol. doi: 10.1001/jamaoncol.2020.0980:ca_ES

Background Seemingly conflicting findings exist regarding the prognostic impact of totally occluded infarct-related arteries (oIRA) in non-ST elevation acute coronary syndromes (NSTE-ACS). Methods Retrospective analysis of prospective multicenter registry data comprising a single-center NSTE-ACS cohort, aimed at assessing the impact of occluded (TIMI flow 0/1) versus patent culprit vessels (pIRA, TIMI flow 2/3) on the composite endpoint of all-cause death and cardiogenic shock events at 30 days. Results Of 568 patients, 183 (32.5%) had oIRA. Male sex, refractory angina, ECG suggestive of multivessel or left main disease, and larger infarct sizes with inferior/posterolateral wall involvement, were identified as highly specific markers of oIRA. Successful culprit-lesion revascularization occurred more frequently in patent than in oIRA (90% vs. 96%; P = 0.013). Conversely, patients with oIRA more frequently achieved successful revascularization of concurrent non-IRAs including chronic total occlusions than did those with pIRA (28% vs. 3%; P = 0.0005). Multivariate analysis revealed neutral effects of oIRA on outcomes and identified incomplete revascularization as a powerful predictor of mortality. Moderation analysis revealed a significant interaction between completeness of revascularization and IRA patency, whereby among the incompletely revascularized patients, those with oIRA enjoyed a significant survival advantage over their counterparts with pIRA (11.8% vs. 28%, adjusted OR 0.34; 95% CI 0.10–0.73; P interaction = 0.012). Conclusions Approximately one third of NSTE-ACS patients in this cohort had oIRA. However, compared with pIRA, the occurrence of oIRA did not portend poor outcomes, likely resulting from the higher rate of incomplete revascularization and increased risk of subsequent mortality in patients with pIRA. These exploratory findings warrant further investigation.

Background: Several de-escalation approaches are under investigation in patients with HER2-positive early breast cancer (EBC). We assessed early metabolic responses to neoadjuvant trastuzumab and pertuzumab (HP) using 18F-FDG PET/CT (FDG-PET) and the possibility of chemotherapy de-escalation using a response–adapted strategy. Methods: PHERGain is a randomised, open-label phase 2 trial conducted in 45 centres from seven European countries. Patients aged ≥18 years with FDG-PET–evaluable, centrally confirmed HER2-positive EBC were randomly allocated (1:4) to receive docetaxel (T), carboplatin (C), and HP (arm A) or HP±endocrine therapy (arm B). Randomisation was stratified by hormone receptor status. Centrally reviewed FDG-PET was performed with pre-randomisation and after two treatment cycles. Arm A patients completed six cycles regardless of FDG-PET results. Arm B/FDG-PET–responders continued HP±endocrine therapy for six cycles; arm B/FDG-PET–nonresponders switched to six cycles of TCHP. Co-primary endpoints were the percentage of arm B/FDG-PET–responders with pathologic complete response (pCR) in the breast and axilla (ypT0/is ypN0) and 3-year invasive disease-free survival (iDFS) of arm B patients. Findings: Between 26 June 2017 and 24 April 2019, 356 patients were randomly assigned to arm A (n=71) or arm B (n=285). pCR occurred in 41 patients in arm A (57.7%, 95% Confidence Interval (CI) 47.4–69.4%) and 101 in arm B (35.4%, 95% CI 29.9–41.3%). Among arm B patients, 227 (79.6%) were FDG-PET–responders, 86 (37.9%, 95% CI 31.6–44.5%) of whom obtained pCR. No new safety signals were identified. Global health status declined ≥10% in 65.0% and 35.5% of patients in arms A and B, respectively. Interpretation: FDG-PET identified HER2-positive EBC patients likely to benefit from chemotherapy-free dual HER2 blockade with HP and a reduced impact on global health status. Depending on iDFS results, this strategy could select patients not requiring chemotherapy. Trial Registration: This trial is registered with EudraCT (‎2016-002676-27) and ClinicalTrials.gov (NCT03161353). Funding Statement: The study was conceived and designed by Medica Scientia Innovation Research (MEDSIR) in collaboration with F. Hoffmann-La Roche Ltd, which funded the study and provided the study drugs. MEDSIR, as legal sponsor of the study, is responsible for compliance with all clinical and regulatory procedures and adherence to the study protocol. Declaration of Interests: JMP-G reports to have a consulting role for Roche and Lilly, and travel expenses from Roche. GG reports research funding to the Institution from Roche and that an immediate family member received personal fees from Roche outside the submitted work. MRB reports to have a consulting role for Novartis, Pfizer, MSD, and to be part of speaker bureau for Pfizer, Novartis, Roche, Lilly, Astrazeneca. AS reports to have a consulting role for Roche and EISAI, to be part of speaker bureau for Roche and EISAI, expert testimony for ESIAI and Roche, and travel expenses from Roche and Pfizer. BB reports to have a consulting role for Genentech and MSD, to be part of speaker bureau for Genentech, and travel expenses from Pfizer. SE-de-R reports to have a consulting role for Roche, Pierre-Fabre, Eisai, research funding from Synthon and Roche, and travel expenses from Roche, Pierre-Fabre, and Daiichi Sankyo. AP reports honoraria from Pfizer, Novartis, Roche, MSD Oncology, Lilly, Daiichi Sankyo, Amgen, to have a consulting role for Amgen, Roche, Novartis, Pfizer, Brystol-Myers Squibb, Boehringer, PUMA Biotechnology, Oncolytics Biotech, Daiichi Sankyo, Abbvie, NanoString Technologies, research funding to the Institution from Roche, Novartis, Incyte, PUMA Biotechnology, to have intellectual property (PCT/EP2016/080056: HER2 AS A PREDICTOR OF RESPONSE TO DUAL HER2 BLOCKADE IN THE ABSENCE OF CYTOTOXIC THERAPY; WO/2018/096191. Chemoendocrine score (CES) Based on PAM50 for breast cancer with positive hormone receptors with an intermediate risk of recurrence), travel expenses from Daiichi Sankyo, other relationship with Oncolytics, Peptomyc S.L., and that an immediate family member is an employee of Novartis. MC reports to have a consulting role for Pierre-Fabre, Pfizer, OBI Pharma, Celldex, AstraZeneca, and honoraria from Novartis. NA reports to have a consulting role for Pfizer, Novartis, Roche, AstraZeneca, and Lilly, and travel expenses from Pfizer, Novartis, Roche, and AstraZeneca. MS-C reports honoraria from MEDSIR, Syntax for Science, and Nestle, to have a consulting role for MEDSIR, Syntax for Science, and Nestle, to be part of speaker bureau for MEDSIR, Syntax for Science, Roche, research funding from MEDSIR, Syntax for Science, and Roche, and travel expenses from MEDSIR, Syntax for Science, and Roche. AM is a full-time employee of MEDSIR. JC reports to have a consulting role for Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp&Dohme, GSK, Leuko, Bioasis, and Clovis Oncology, honoraria from Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, and Daiichi Sankyo, research funding to the Institution from Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, and Queen Mary University of London, and intellectual property for MEDSIR. AL-C reports leadership for Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, and MSD, intellectual property for MEDSIR and Initia-Research, to have a consulting role for Lilly, Roche, Pfizer, Novartis, Pierre-Fabre, GenomicHealth, and GSK, to be part of speaker bureau for Lilly, AstraZeneca, and MSD, research funding from Roche, Foundation Medicine, and Pierre-Fabre, Agendia, and travel expenses from Roche, Lilly, Novartis, Pfizer, and AstraZeneca. LC, NR, NM, CA, FD, and KK have nothing to declare. Ethics Approval Statement: This study was performed in accordance with guidelines of the International Conference on 205 Harmonization and ethical principles outlined in the Declaration of Helsinki. Written informed 206 consent was obtained before enrolment, and all participants agreed to study-specific procedures. 207 Approvals from appropriate regulatory authorities and ethics committees were obtained.

Background Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. Patients and methods In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8mg/kg loading dose, then 6mg/kg every 3weeks (q3w)] and pertuzumab (840mg loading dose, then 420mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). Results Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54years; 29% had received prior trastuzumab. Median treatment duration was 16months for pertuzumab and trastuzumab and 4months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9–22.7] months overall (19.6, 23.0 and 18.1months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%–82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). Conclusions Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile. ClinicalTrials.gov NCT01572038.

The minor allele (C) of the single-nucleotide polymorphism (SNP) rs11212617, located near the ataxia telangiectasia mutated (ATM) gene, has been associated with an increased likelihood of treatment success with metformin in type 2 diabetes. We herein investigated whether the same SNP would predict clinical response to neoadjuvant metformin in women with early breast cancer (BC). Methods: DNA was collected from 79 patients included in the intention-to-treat population of the METTEN study, a phase 2 clinical trial of HER2-positive BC patients randomized to receive either metformin combined with anthracycline/taxane-based chemotherapy and trastuzumab or equivalent regimen without metformin, before surgery. SNP rs11212617 genotyping was assessed using allelic discrimination by quantitative polymerase chain reaction. Results: Logistic regression analyses revealed a significant relationship between the rs11212617 genotype and the ability of treatment arms to achieve a pathological complete response (pCR) in patients (odds ratio [OR]genotype×arm = 10.33, 95% confidence interval [CI]: 1.29–82.89, p = 0.028). In the metformin-containing arm, patients bearing the rs11212617 C allele had a significantly higher probability of pCR (ORA/C,C/C = 7.94, 95%CI: 1.60–39.42, p = 0.011). Conversely, no association was found between rs11212617 and clinical response in the reference arm (ORA/C,C/C = 0.77, 95%CI: 0.20–2.92, p = 0.700). After controlling for tumor size and hormone receptor status, the rs11212617 C allele remained a significant predictor of pCR solely in the metformin-containing arm. Conclusions: If reproducible, the rs11212617 C allele might warrant consideration as a predictive clinical biomarker to inform the personalized use of metformin in BC patients This work was supported by grants from the Ministerio de Sanidad, Servicios Sociales e Igualdad (EC10-125, Ayudas para el Fomento de la Investigación Clínica Independiente to BM-C). Work in the Menendez laboratory is supported by the Ministerio de Ciencia e Innovación [Grant SAF2016-80639-P, Plan Nacional de l+D+I, founded by the European Regional Development Fund (EU FEDER), Spain] and by an unrestricted research grant from the Fundació Oncolliga Girona (Lliga catalana d’ajuda al malalt de càncer, Girona)

Poly(ADP‐ribose) polymerase (PARP) inhibitors (PARPi) are effective in cancers with defective homologous recombination DNA repair (HRR), including BRCA1/2‐related cancers. A test to identify additional HRR‐deficient tumors will help to extend their use in new indications. We evaluated the activity of the PARPi olaparib in patient‐derived tumor xenografts (PDXs) from breast cancer (BC) patients and investigated mechanisms of sensitivity through exome sequencing, BRCA1 promoter methylation analysis, and immunostaining of HRR proteins, including RAD51 nuclear foci. In an independent BC PDX panel, the predictive capacity of the RAD51 score and the homologous recombination deficiency (HRD) score were compared. To examine the clinical feasibility of the RAD51 assay, we scored archival breast tumor samples, including PALB2‐related hereditary cancers. The RAD51 score was highly discriminative of PARPi sensitivity versus PARPi resistance in BC PDXs and outperformed the genomic test. In clinical samples, all PALB2‐related tumors were classified as HRR‐deficient by the RAD51 score. The functional biomarker RAD51 enables the identification of PARPi‐sensitive BC and broadens the population who may benefit from this therapy beyond BRCA1/2‐related cancers.

To assess the effect of a 12-day treatment using a vaginal gel based on niosomes containing hyaluronic acid, s-glucan, alpha-glucan oligosaccharide, Coriolus versicolor, Asian centella, Azadirachta indica and Aloe vera on vaginal microbiota, cervical epithelization and vaginal health. Open-label, prospective pilot study conducted in asymptomatic women in daily practice. Cervical epithelization was evaluated by colposcopy using an ectopy epithelization score (from 5: no ectopy to 1: severe ectopy and bleeding), vaginal microbiota using the VaginaStatus-Diagnostic test (Instiut fur Mikrookologie, Herborn, Germany) and further rated by the investigator using a 5-point Liker scale (from 5: normal to 1: very severe deterioration in which all evaluated species were altered), and vaginal health using the Vaginal Health Index. In 21 women, a positive effect to improve epithelization of the cervical mucosa, with a mean score of 4.42 at the final visit as compared to 3.09 at baseline (P

Justificación de la Guía de cribado del cáncer de cuello de útero en España, 2014 El cáncer de cuello uterino (CCU) es la tercera neoplasia más frecuente en el mundo en las mujeres. El cribado de mujeres sanas mediante citología cervical ha demostrado claramente su eficacia, puesto que su aplicación de forma adecuada y sistemática en determinados países ha conseguido reducir en un 70-80% la incidencia y mortalidad por CCU. Este beneficio se debe a la detección de lesiones premalignas asintomáticas cuyo diagnóstico y tratamiento evita su progresión a carcinoma invasor...

h Abstract Objective. To quantify the coverage and monitor the factors associated with opportunistic cervical cytological screening in Spain. Materials and Methods. Population-based survey of selected women through the Access Panel technique representative of the general population. A total of 6,852 women (60%) replied to the questionnaire; 981 (14.3%) were excluded from the analysis because they did not meet the screening criteria. Data were adjusted for regions, age group, socioeconomic level (SEL), and municipality size. Moreover, information was collected on preventive gynecological revisions received. Categorical variables were evaluated through the W 2 test of heterogeneity or through a liner test for trend. Multivariate prevalence odds ratios were used to identify statistically significant determinants of screening using logistic regression modeling. Results. The percentage of women 18 to 65 years old with a Pap smear within the last 3 years was 75.6%. Insufficient coverage was observed in women older than 55 years (66%), who live in rural areas (66%), with lower SEL (65%), and in some regions (61%Y66%). The factors positively associated with screening were age 26 to 55 years, certain regions, higher SEL, larger municipality size, ever being pregnant, early age at first sexual intercourse, knowledge about cervical cancer and human papillomavirus, and, very strongly, ever use of contraceptive methods. An overuse of cytology can be assumed, as a result of opportunistic screening. Conclusions. In Spain, the coverage of cytological screening reached 75% of the population, but with inefficiencies in some aspects. To rationalize its use, the Spanish consensus screening protocol must be followed. h

Background and purpose Information received by IBD patients about their disease is of particular importance. The objective of the study was to determine the information resources these patients used, together with their perceived information gaps and expected preferences. Patients and methods A prospective, observational, cross-sectional study conducted on IBD patients attending 13 Spanish hospitals during 2008. Patients completed a semi-structured 52-question survey. Results Survey was adequately completed by 379 of 385 patients (98%), of whom 57% had Crohn's disease and 43% ulcerative colitis. Mean patient age was 37.9 years (range, 16–76 years). Gastroenterologists were the most commonly used resource (98%), followed by the Internet (60%), and general practitioners (50%). More than 90% reported good to excellent satisfaction with gastroenterologists, nurses, and patients’ associations. Only 56% considered their information needs to be covered. The Internet was mostly used by young patients and those with a high education level. In the future, 85% of the patients would like to receive information from the gastroenterologists, and 92% by face-to-face interviews. Patients mainly want additional information on treatment (medical and surgical), clinical manifestations, cancer, and mortality risks. They also think that they are poorly informed about their social and work rights, risks of cancer and death, and research trials. Conclusions Patients with IBD use and prefer gastroenterologists as the main source of information, but only half of them consider their information needs to be covered.

Introduccion y objetivos Se analizan los determinantes y el valor pronostico de la dispersion del intervalo QT en un grupo de pacientes consecutivos ingresados por insuficiencia cardiaca. Metodos Se estudiaron a 122 pacientes consecutivos ingresados por insuficiencia cardiaca en los que se obtuvo una medicion fiable de la dispersion del intervalo QT (QT maximo – QT minimo) en el electrocardiograma inicial. Se registraron los principales datos clinicos, analiticos y ecocardiograficos. Se estudio un grupo control (n = 35) ajustado por edad y sexo al grupo de estudio. Resultados El grupo de estudio mostro una mayor dispersion del intervalo QT que el grupo control (62 ± 30 frente a 40 ± 21 ms; p = 0,01). Los pacientes con una dispersion del intervalo QT > 80 ms (n = 50; 41%) presentaron una menor natremia (138 ± 6 frente a 141 ± 4 mEq/l; p = 0,01), una mayor probabilidad de etiologia isquemica (52 frente a 33%; riesgo relativo = 2,2; intervalo de confianza del 95%, 1,05–4,7; p = 0,04), una mayor mortalidad en el primer ano (el 20 frente al 6%; riesgo relativo = 4,7; intervalo de confianza del 95%, 1,3–16; p = 0,01) y global (el 38 frente al 19%; riesgo relativo = 3,4; intervalo de confianza del 95%, 1,3–8,6; p = 0,01) que el grupo con dispersion del intervalo QT Conclusiones Los pacientes con insuficiencia cardiaca presentan una dispersion aumentada del intervalo QT. Dicho parametro constituye un indice sencillo que orienta hacia una etiologia isquemica y puede ayudar en la estratificacion pronostica.

To assess and analyze the information and recommendations provided by Google Web Search™ (Google) in relation to web searches on the HPV vaccine, indications for females and males and possible adverse effects.|In the comprehensive analysis of results, 72.2% of websites offer information favorable to HPV vaccination, with varying degrees of content detail, vs. 27.8% with highly dissuasive content in relation to HPV vaccination. The most frequent type of site is the blog or forum. The information found is frequently incomplete, poorly structured, and often lacking in updates, bibliography and adequate citations, as well as sound credibility criteria (scientific association accreditation and/or trust mark system).|Descriptive cross-sectional study of the results of 14 web searches. Comprehensive analysis of results based on general recommendation given (favorable/dissuasive), as well as compliance with pre-established criteria, namely design, content and credibility. Sub-analysis of results according to site category: general information, blog / forum and press.|Google, as a tool which users employ to locate medical information and advice, is not specialized in providing information that is necessarily rigorous or valid from a scientific perspective. Search results and ranking based on Google's generalized algorithms can lead users to poorly grounded opinions and statements, which may impact HPV vaccination perception and subsequent decision making.

Stenotrophomonas (Xanthomonas) maltophilia is a rare cause of endocarditis. The extensive resistance of this organism to several antibiotics leaves few options for antimicrobial therapy. In vitro synergism of the combination of trimethoprim-sulfamethoxazole (TMP-SMZ) and ticarcillin/clavulanic acid (TIC/CA) has been demonstrated. To our knowledge, we report the first case of ventriculoatrial cerebrospinal fluid shunt-associated endocarditis due to S. maltophilia. The patient was cured with combination therapy with TMP-SMZ and TIC/CA along with catheter removal. This is also the first report of S. maltophilia endocarditis successfully treated with this antibiotic combination. In a review of the medical literature, only 16 cases of S. maltophilia endocarditis were found. Most patients were intravenous drug users (43.8%) or had either prosthetic heart valves (50%) or an indwelling vascular catheter (18.8%). Although S. maltophilia is usually considered a nosocomial pathogen, about one-half of the cases were community-acquired. Twelve of sixteen patients had left-sided endocarditis. Therapy with a combination of two or more antibiotics was employed in most cases. Seven patients had been given TMP-SMZ therapy, but none had been treated with TIC/CA before. One-half of the patients required cardiac surgery. The overall mortality rate was 33%. Although the optimal antibiotic treatment for S. maltophilia endocarditis remains unknown, the case reported herein reinforces in vitro findings that the combination of TMP-SMZ and TIC/CA may be effective therapy.

This section focuses on different aspects of the individualization of hormone treatment in breast cancer. This includes tumor-related biological factors such as expression of hormone receptors, HER-2, and Ki-67; host-related factors such as CYP2D6 or body mass index, and risk and/or development of specific toxicities and treatment adherence. The best predictor of response to hormonal interventions is the expression of hormone receptors, in particular, estrogen receptors. Treatment adherence and compliance are key factors and strategies aiming to identify and intervene when patients are at risk of abandoning treatment. Currently, routine assessment of CYP2D6 is not recommended to guide tamoxifen treatment. Likewise, there are no criteria regarding bone mass density, lipid profile, or arthralgias to recommend one class of agent versus another. Aromatase inhibitors should not be administered to patients who are pre- or perimenopausal.

Successful implementation of Human Papillomavirus (HPV) vaccine in each country can only be achieved from a complementary and synergistic perspective, integrating all the different points of view of the diverse related professionals. It is this context where the Spanish HPV Vaccine Consensus Group (Grupo Español de Consenso sobre la Vacuna VPH, GEC-VPH) was created. GEC-VPH philosophy, objectives and experience are reported in this article, with particular attention to the management of negative publicity and anti-vaccine groups. Initiatives as GEC-VPH--adapted to each country's particular idiosyncrasies--might help to overcome the existing barriers and to achieve wide and early implementation of HPV vaccination.

Background Extensive information on cervical cancer is currently available. Its effectiveness in reducing anxiety in women receiving abnormal Pap tests is not clear. We investigated current practices of communicating abnormal Pap results to evaluate women's reactions and determine the sources of information they use subsequently. Methods A self-administered questionnaire-based study was performed in 1475 women in France, Spain and Portugal who had received an abnormal Pap smear result in the 12 months prior to completing the questionnaire. Questions covered methods of communication of the result, emotional reactions, support received (from the physician and entourage), and information sources, using pre-specified check box options and rating scales. Data were analyzed by country. Results Pap test results were mostly communicated by phone to Spanish women (76%), while physician letters were common in France (59%) and Portugal (36%). Frequent reactions were anxiety, panic and stress, which were less common in Spanish women than their French and Portuguese counterparts. After discussing with their physician, half of the participants were worried, despite rating highly the psychological support received. Over 90% of women in each country discussed their results with family or friends. Partners provided a high level of support. Overall, the abnormal diagnosis and consequences had a low to medium impact on daily, professional and family life and their relationships with their partner. Impact was higher in Spanish women than the French or Portuguese. Information on the diagnosis and its treatment was rated average, and nearly 80% of participants wanted more information, notably French women. Preferred sources were the physician and the Internet. Conclusions Women expressed a strong wish for more information about cervical cancer and other HPV-related diseases, and that their physician play a major role in its provision and in support. There was a heavy reliance on the close entourage and the Internet for information, highlighting the need for dissemination of accurate material. Differences between countries suggest information management strategies may need to be tailored to different geographical regions.