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2. |
- Zaborowski, AM, et al.
(författare)
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Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
- 2022
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
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Tidskriftsartikel (refereegranskat)abstract
- In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.
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4. |
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5. |
- Govoni, F., et al.
(författare)
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A radio ridge connecting two galaxy clusters in a filament of the cosmic web
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6444, s. 981-984
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Tidskriftsartikel (refereegranskat)abstract
- Galaxy clusters are the most massive gravitationally bound structures in the Universe. They grow by accreting smaller structures in a merging process that produces shocks and turbulence in the intracluster gas. We observed a ridge of radio emission connecting the merging galaxy clusters Abell 0399 and Abell 0401 with the Low-Frequency Array (LOFAR) telescope network at 140 megahertz. This emission requires a population of relativistic electrons and a magnetic field located in a filament between the two galaxy clusters. We performed simulations to show that a volume-filling distribution of weak shocks may reaccelerate a preexisting population of relativistic particles, producing emission at radio wavelengths that illuminates the magnetic ridge.
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6. |
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7. |
- Jerusalem, G, et al.
(författare)
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Continuous versus intermittent extended adjuvant letrozole for breast cancer: Final results of randomized phase 3 SOLE (Study of Letrozole Extension) and SOLE Estrogen Substudy.
- 2021
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 32:10, s. 1256-1266
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Tidskriftsartikel (refereegranskat)abstract
- Late recurrences in postmenopausal women with hormone receptor-positive breast cancers remain an important challenge. Avoidance or delayed development of resistance represents the main objective in extended endocrine therapy. In animal models, resistance was reversed with restoration of circulating estrogen level during interruption of letrozole treatment. This phase 3 randomized, open-label Study of Letrozole Extension (SOLE) studied the effect of extended intermittent letrozole treatment in comparison with continuous letrozole. In parallel, the SOLE estrogen sub-study (SOLE-EST) analyzed the level of estrogen during the interruption of treatment.SOLE enrolled 4884 postmenopausal women with hormone receptor-positive, lymph node-positive, operable breast cancer between December 2007 and October 2012 and among them, 104 patients were enrolled in SOLE-EST. They must have undergone local treatment and have completed 4-6 years of adjuvant endocrine therapy. Patients were randomized between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day during 9 months followed by a 3-month interruption in years 1-4 and then 2.5 mg/day during all year 5).Intention-to-treat population included 4851 women in SOLE (n=2425 in intermittent and n=2426 in continuous letrozole groups) and 103 women in SOLE-EST (n=78 in intermittent and n=25 in continuous letrozole groups). After a median follow-up of 84 months, 7-year disease-free survival was 81.4% in intermittent group and 81.5% in continuous group (hazard ratio: 1.03, 95%CI: 0.91-1.17). Reported adverse events were similar in both groups. Circulating estrogen recovery was demonstrated within 6 weeks after the stop of letrozole treatment.Extended adjuvant endocrine therapy by intermittent administration of letrozole did not improve disease-free survival compared to continuous use despite the recovery of circulating estrogen level. The similar disease-free survival coupled with previously reported quality-of-life advantages suggest intermittent extended treatment is a valid option for patients who require or prefer a treatment interruption.
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8. |
- Luen, S J, et al.
(författare)
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Genomic characterisation of hormone receptor-positive breast cancer arising in very young women.
- 2023
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology. - : Elsevier BV. - 1569-8041. ; 34:4, s. 397-409
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Tidskriftsartikel (refereegranskat)abstract
- Very young premenopausal women diagnosed with hormone receptor-positive, HER2-negative (HR+HER2-) early breast cancer (EBC) have higher rates of recurrence and death for reasons that remain largely unexplained.Genomic sequencing was applied to HR+HER2- tumours from patients enrolled in the SOFT clinical trial to determine genomic drivers that are enriched in young premenopausal women. Genomic alterations were characterised using next-generation sequencing from a subset of 1,276 patients (deep targeted sequencing, N=1258; whole-exome sequencing in a young-age, case-control subsample, N=82). We defined copy number (CN) subgroups and assessed for features suggestive of homologous recombination deficiency (HRD). Genomic alteration frequencies were compared between young premenopausal women (<40 years) and older premenopausal women (≥40 years), and assessed for associations with distant recurrence-free interval (DRFI), and overall survival (OS).Younger women (<40 years, N=359) compared with older women (≥40 years, N=917) had significantly higher frequencies of mutations in GATA3 (19%vs16%) and CN-amplifications (47%vs26%), but significantly lower frequencies of mutations in PIK3CA (32%vs47%), CDH1 (3%vs9%), and MAP3K1 (7%vs12%). Additionally, significantly higher frequencies of features suggestive of HRD (27%vs21%), and a higher proportion of PIK3CA mutations with concurrent CN-amplifications (23%vs11%).Genomic features suggestive of HRD, PIK3CA mutations with CN-amplifications, and CN-amplifications associated with significantly worse DRFI and OS compared with those without these features. These poor prognostic features were enriched in younger patients: present in 72% of patients aged <35 years, 54% aged 35-39 years, and 40% ≥40 years. Poor prognostic features (N=584[46%]) vs none (N=692[54%]) had an 8-year DRFI of 84%vs94% and OS of 88%vs96%. Younger women (<40) had the poorest outcomes: 8-year DRFI 74%vs85% and OS of 80%vs93% respectively.These results provide insights into genomic alterations that are enriched in young women with HR+HER2-EBC, provide rationale for genomic subgrouping, and highlight priority molecular targets for future clinical trials.
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9. |
- Gonzalez-Ericsson, Paula, et al.
(författare)
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The path to a better biomarker: application of a risk management framework for the implementation of PD‐L1 and TILs as immuno‐oncology biomarkers into breast cancer clinical trials and daily practice
- 2020
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Ingår i: Journal of Pathology. - : Wiley. - 1096-9896 .- 0022-3417. ; 250:5, s. 667-684
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Forskningsöversikt (refereegranskat)abstract
- Immune checkpoint inhibitor therapies targeting PD‐1/PD‐L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD‐L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab‐paclitaxel. However, concerns regarding variability between immunohistochemical PD‐L1 assay performance and inter‐reader reproducibility have been raised. High tumor‐infiltrating lymphocytes (TILs) have also been associated with response to PD‐1/PD‐L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin–stained slides and have shown reliable inter‐reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD‐L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD‐L1 and TIL analyses as a more comprehensive immuno‐oncological biomarker for patient selection for PD‐1/PD‐L1 inhibition‐based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk‐management framework that may help mitigate the risks of suboptimal patient selection for immuno‐therapeutic approaches in clinical trials and daily practice based on combined TILs/PD‐L1 assessment in BC.
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10. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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11. |
- Eratne, D., et al.
(författare)
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Cerebrospinal fluid neurofilament light chain differentiates primary psychiatric disorders from rapidly progressive, Alzheimer's disease and frontotemporal disorders in clinical settings
- 2022
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:11, s. 2218-2233
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Many patients with cognitive and neuropsychiatric symptoms face diagnostic delay and misdiagnosis. We investigated whether cerebrospinal fluid (CSF) neurofilament light (NfL) and total-tau (t-tau) could assist in the clinical scenario of differentiating neurodegenerative (ND) from psychiatric disorders (PSY), and rapidly progressive disorders. Methods Biomarkers were examined in patients from specialist services (ND and PSY) and a national Creutzfeldt-Jakob registry (Creutzfeldt-Jakob disease [CJD] and rapidly progressive dementias/atypically rapid variants of common ND, RapidND). Results A total of 498 participants were included: 197 ND, 67 PSY, 161 CJD, 48 RapidND, and 20 controls. NfL was elevated in ND compared to PSY and controls, with highest levels in CJD and RapidND. NfL distinguished ND from PSY with 95%/78% positive/negative predictive value, 92%/87% sensitivity/specificity, 91% accuracy. NfL outperformed t-tau in most real-life clinical diagnostic dilemma scenarios, except distinguishing CJD from RapidND. Discussion We demonstrated strong generalizable evidence for the diagnostic utility of CSF NfL in differentiating ND from psychiatric disorders, with high accuracy.
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12. |
- Eratne, D., et al.
(författare)
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Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders
- 2023
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Ingår i: Australian and New Zealand Journal of Psychiatry. - 0004-8674. ; 58:1, s. 70-81
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Blood biomarkers of neuronal injury such as neurofilament light (NfL) show promise to improve diagnosis of neurodegenerative disorders and distinguish neurodegenerative from primary psychiatric disorders (PPD). This study investigated the diagnostic utility of plasma NfL to differentiate behavioural variant frontotemporal dementia (bvFTD, a neurodegenerative disorder commonly misdiagnosed initially as PPD), from PPD, and performance of large normative/reference data sets and models. Methods: Plasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), bvFTD (n = 22), and compared to the reference cohort (Control Group 2, n = 1926, using GAMLSS modelling), and age-matched controls (Control Group 1, n = 96, using general linear models). Results: Large differences were seen between bvFTD (mean NfL 34.9 pg/mL) and all PPDs and controls (all < 11 pg/mL). NfL distinguished bvFTD from PPD with high accuracy, sensitivity (86%), and specificity (88%). GAMLSS models using reference Control Group 2 facilitated precision interpretation of individual levels, while performing equally to or outperforming models using local controls. Slightly higher NfL levels were found in BPAD, compared to controls and TRS. Conclusions: This study adds further evidence on the diagnostic utility of NfL to distinguish bvFTD from PPD of high clinical relevance to a bvFTD differential diagnosis, and includes the largest cohort of BPAD to date. Using large reference cohorts, GAMLSS modelling and the interactive Internet-based application we developed, may have important implications for future research and clinical translation. Studies are underway investigating utility of plasma NfL in diverse neurodegenerative and primary psychiatric conditions in real-world clinical settings.
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13. |
- Joseph, A, et al.
(författare)
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Metabolic features of cancer cells impact immunosurveillance
- 2021
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Ingår i: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Tumors rewire their metabolism to achieve robust anabolism and resistance against therapeutic interventions like cisplatin treatment. For example, a prolonged exposure to cisplatin causes downregulation of pyridoxal kinase (PDXK), the enzyme that generates the active vitamin B6, and upregulation of poly ADP-ribose (PAR) polymerase-1 (PARP1) activity that requires a supply of nicotinamide (vitamin B3) adenine dinucleotide. We investigated the impact of the levels of PDXK and PAR on the local immunosurveillance (ie, density of the antigen presenting cells and adaptive immune response by CD8 T lymphocytes) in two different tumor types.MethodsTumors from patients with locally advanced cervical carcinoma (LACC) and non-small cell lung cancer (NSCLC) were stained for PAR, PDXK, dendritic cell lysosomal associated membrane glycoprotein (DC-LAMP) and CD8 T cell infiltration. Their correlations and prognostic impact were assessed. Cisplatin-resistant NSCLC cell clones isolated from Lewis-lung cancer (LLC) cells were evaluated for PAR levels by immunoblot. Parental (PARlow) and cisplatin-resistant (PARhigh) clones were subcutaneously injected into the flank of C57BL/6 mice. Tumors were harvested to evaluate their immune infiltration by flow cytometry.ResultsThe infiltration of tumors by CD8 T and DC-LAMP+ cells was associated with a favorable overall survival in patients with LACC (p=0.006 and p=0.008, respectively) and NSCLC (p<0.001 for both CD8 T and DC-LAMP cells). We observed a positive correlation between PDXK expression and the infiltration by DC-LAMP (R=0.44, p=0.02 in LACC, R=0.14, p=0.057 in NSCLC), and a negative correlation between PAR levels and CD8 T lymphocytes (R=−0.39, p=0.034 in LACC, R=−0.18, p=0.017 in NSCLC). PARP1 is constitutively hyperactivated in cisplatin-resistant LLC cells manifesting elevated intracellular levels of poly(ADP-ribosyl)ated proteins (PARhigh). Tumors formed by such cancer cells injected into immunocompetent mice were scarcely infiltrated by CD8 T (p=0.028) and antigen presenting cells (p=0.086).ConclusionsOncometabolic features can impact local immunosurveillance, providing new functional links between cisplatin resistance and therapeutic failure.
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14. |
- Amgad, M, et al.
(författare)
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Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group
- 2020
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 6:1, s. 16-
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Tidskriftsartikel (refereegranskat)abstract
- Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.
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16. |
- Fabiano, Simone, et al.
(författare)
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Charge transport orthogonality in all-polymer blend transistors, diodes, and solar cells
- 2014
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Ingår i: Advanced Energy Materials. - : Wiley-VCH Verlag. - 1614-6832 .- 1614-6840. ; 4:6, s. 1301409-
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Tidskriftsartikel (refereegranskat)abstract
- Polymer aggregation and phase separation of polymer-polymer blends are effectively tuned from self-stratified to laterally phase-separated by adjusting the relative solubility of the two polymers in the mixture. This is found to dramatically alter the charge transport characteristics from a preferential in-plane to an out-of-plane direction, revealing the critical dependence of the resulting device performance on the film morphology and structure of the active layer. © 2013 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim.
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17. |
- Galluzzi, L, et al.
(författare)
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Consensus guidelines for the definition, detection and interpretation of immunogenic cell death
- 2020
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Ingår i: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.
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18. |
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19. |
- DInnocenzo, V., et al.
(författare)
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Two-dimensional charge transport in molecularly ordered polymer field-effect transistors
- 2016
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Ingår i: JOURNAL OF MATERIALS CHEMISTRY C. - : ROYAL SOC CHEMISTRY. - 2050-7526 .- 2050-7534. ; 4:47, s. 11135-11142
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Tidskriftsartikel (refereegranskat)abstract
- Nanometer-thick Langmuir-Schafer monolayers of an electron transporting polymer display charge transport, optical and electro-optical properties that do not depend on the number of layers deposited one above the other. This phenomenon can be rationalized with the micro-structure of the specific multi-layers, which introduces an interlayer hopping penalty confining transport to a neat 2D regime, with a channel not extending beyond a single similar to 3 nm thick polymer strand, as confirmed by kinetic Monte Carlo simulations. Such findings are critical to establish a quantitative structure-property nexus in high mobility polymer semiconductors and in the control of charge transport at a molecular scale.
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20. |
- Hudeček, Jan, et al.
(författare)
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Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials
- 2020
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Ingår i: npj Breast Cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 6:1
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Forskningsöversikt (refereegranskat)abstract
- Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting.
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21. |
- Leon-Ferre, Roberto A., et al.
(författare)
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Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer
- 2024
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Ingår i: JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION. - 0098-7484 .- 1538-3598. ; 331:13, s. 1135-1144
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Tidskriftsartikel (refereegranskat)abstract
- Key PointsQuestionIn patients with early-stage triple-negative breast cancer (TNBC) treated with locoregional therapy but without adjuvant or neoadjuvant chemotherapy, is a higher abundance of tumor-infiltrating lymphocytes (TIL) in breast cancer tissue associated with better survival? FindingsIn this retrospective analysis of 1966 participants with early-stage TNBC treated with locoregional therapy but without adjuvant or neoadjuvant chemotherapy, survival rates were 90% for patients with a TIL level of 50% or greater, compared with 72% for patients with a TIL level of less than 30% at 5-year follow-up. MeaningIn patients with early-stage TNBC treated with locoregional therapy only, higher TIL levels in breast cancer tissue were associated with improved survival. ImportanceThe association of tumor-infiltrating lymphocyte (TIL) abundance in breast cancer tissue with cancer recurrence and death in patients with early-stage triple-negative breast cancer (TNBC) who are not treated with adjuvant or neoadjuvant chemotherapy is unclear. ObjectiveTo study the association of TIL abundance in breast cancer tissue with survival among patients with early-stage TNBC who were treated with locoregional therapy but no chemotherapy. Design, Setting, and ParticipantsRetrospective pooled analysis of individual patient-level data from 13 participating centers in North America (Rochester, Minnesota; Vancouver, British Columbia, Canada), Europe (Paris, Lyon, and Villejuif, France; Amsterdam and Rotterdam, the Netherlands; Milan, Padova, and Genova, Italy; Gothenburg, Sweden), and Asia (Tokyo, Japan; Seoul, Korea), including 1966 participants diagnosed with TNBC between 1979 and 2017 (with follow-up until September 27, 2021) who received treatment with surgery with or without radiotherapy but no adjuvant or neoadjuvant chemotherapy. ExposureTIL abundance in breast tissue from resected primary tumors. Main Outcomes and MeasuresThe primary outcome was invasive disease-free survival [iDFS]. Secondary outcomes were recurrence-free survival [RFS], survival free of distant recurrence [distant RFS, DRFS], and overall survival. Associations were assessed using a multivariable Cox model stratified by participating center. ResultsThis study included 1966 patients with TNBC (median age, 56 years [IQR, 39-71]; 55% had stage I TNBC). The median TIL level was 15% (IQR, 5%-40%). Four-hundred seventeen (21%) had a TIL level of 50% or more (median age, 41 years [IQR, 36-63]), and 1300 (66%) had a TIL level of less than 30% (median age, 59 years [IQR, 41-72]). Five-year DRFS for stage I TNBC was 94% (95% CI, 91%-96%) for patients with a TIL level of 50% or more, compared with 78% (95% CI, 75%-80%) for those with a TIL level of less than 30%; 5-year overall survival was 95% (95% CI, 92%-97%) for patients with a TIL level of 50% or more, compared with 82% (95% CI, 79%-84%) for those with a TIL level of less than 30%. At a median follow-up of 18 years, and after adjusting for age, tumor size, nodal status, histological grade, and receipt of radiotherapy, each 10% higher TIL increment was associated independently with improved iDFS (hazard ratio [HR], 0.92 [0.89-0.94]), RFS (HR, 0.90 [0.87-0.92]), DRFS (HR, 0.87 [0.84-0.90]), and overall survival (0.88 [0.85-0.91]) (likelihood ratio test, P<10e-6). Conclusions and RelevanceIn patients with early-stage TNBC who did not undergo adjuvant or neoadjuvant chemotherapy, breast cancer tissue with a higher abundance of TIL levels was associated with significantly better survival. These results suggest that breast tissue TIL abundance is a prognostic factor for patients with early-stage TNBC. This study of patients with early-stage triple-negative breast cancer not treated with adjuvant or neoadjuvant chemotherapy analyzes the association between tumor-infiltrating lymphocyte levels, cancer recurrence, and survival.
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22. |
- Pitaro, Matteo, et al.
(författare)
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A carbazole-based self-assembled monolayer as the hole transport layer for efficient and stable Cs(0.25)FA(0.75)Sn(0.5)Pb(0.5)I(3) solar cells
- 2023
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Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 11:22, s. 11755-11766
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Tidskriftsartikel (refereegranskat)abstract
- Mixed tin/lead (Sn/Pb) perovskites have the potential to achieve higher performances in single junction solar cells compared to Pb-based compounds. The best Sn/Pb based devices are fabricated in a p-i-n structure, and PEDOT:PSS is frequently utilized as the hole transport layer, even if there are many doubts on a possible detrimental role of this conductive polymer. Here, we propose the use of [2-(9H-carbazol-9-yl)ethyl]phosphonic acid (2PACz) and [2-(3, 6-dibromo-9H-carbazol-9-yl) ethyl] phosphonic acid (Br-2PACz) as substitutes for PEDOT:PSS. By using Cs(0.25)FA(0.75)Sn(0.5)Pb(0.5)I(3) as the active layer, we obtained record efficiencies as high as 19.51% on Br-2PACz, while 18.44% and 16.33% efficiencies were obtained using 2PACz and PEDOT:PSS, respectively. In addition, the implemented monolayers enhance both the shelf lifetime of the device as well as the operational stability. Finally, the Br-2PACz-based devices maintained 80% of their initial efficiency under continuous illumination for 230 h, and after being stored in a N-2 atmosphere for 4224 h (176 days).
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23. |
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24. |
- Eratne, D., et al.
(författare)
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Plasma neurofilament light chain protein is not increased in treatment-resistant schizophrenia and first-degree relatives
- 2022
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Ingår i: Australian and New Zealand Journal of Psychiatry. - : SAGE Publications. - 0004-8674 .- 1440-1614. ; 56:10
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Schizophrenia, a complex psychiatric disorder, is often associated with cognitive, neurological and neuroimaging abnormalities. The processes underlying these abnormalities, and whether a subset of people with schizophrenia have a neuroprogressive or neurodegenerative component to schizophrenia, remain largely unknown. Examining fluid biomarkers of diverse types of neuronal damage could increase our understanding of these processes, as well as potentially provide clinically useful biomarkers, for example with assisting with differentiation from progressive neurodegenerative disorders such as Alzheimer and frontotemporal dementias. Methods: This study measured plasma neurofilament light chain protein (NfL) using ultrasensitive Simoa technology, to investigate the degree of neuronal injury in a well-characterised cohort of people with treatment-resistant schizophrenia on clozapine (n = 82), compared to first-degree relatives (an at-risk group, n = 37), people with schizophrenia not treated with clozapine (n = 13), and age- and sex-matched controls (n = 59). Results: We found no differences in NfL levels between treatment-resistant schizophrenia (mean NfL, M = 6.3 pg/mL, 95% confidence interval: [5.5, 7.2]), first-degree relatives (siblings, M = 6.7 pg/mL, 95% confidence interval: [5.2, 8.2]; parents, M after adjusting for age = 6.7 pg/mL, 95% confidence interval: [4.7, 8.8]), controls (M = 5.8 pg/mL, 95% confidence interval: [5.3, 6.3]) and not treated with clozapine (M = 4.9 pg/mL, 95% confidence interval: [4.0, 5.8]). Exploratory, hypothesis-generating analyses found weak correlations in treatment-resistant schizophrenia, between NfL and clozapine levels (Spearman's r = 0.258, 95% confidence interval: [0.034, 0.457]), dyslipidaemia (r = 0.280, 95% confidence interval: [0.064, 0.470]) and a negative correlation with weight (r = -0.305, 95% confidence interval: [-0.504, -0.076]). Conclusion: Treatment-resistant schizophrenia does not appear to be associated with neuronal, particularly axonal degeneration. Further studies are warranted to investigate the utility of NfL to differentiate treatment-resistant schizophrenia from neurodegenerative disorders such as behavioural variant frontotemporal dementia, and to explore NfL in other stages of schizophrenia such as the prodome and first episode.
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25. |
- Manca, M., et al.
(författare)
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Tracing charge transfer states in polymer:fullerene bulk-heterojunctions
- 2013
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Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry (RSC). - 2050-7488 .- 2050-7496. ; 1:25, s. 7321-7325
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Tidskriftsartikel (refereegranskat)abstract
- Charge transfer state emission in organic bulk-heterojunctions has been demonstrated to be an important loss mechanism for this reason a better understanding of the nature and origin of the charge transfer state is fundamental for the improvement of organic solar cells. Here, the relationship between photophysical and morphological features of a prototypical organic bulk-heterojunction is investigated in blends with different donor-acceptor ratios. By correlating imaging with photoluminescence spectra measured in different areas of the blends, the charge transfer state emission is unambiguously assigned to microscopical regions in which the intermixing of the two organic semiconductors is higher.
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26. |
- Piliego, C., et al.
(författare)
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Charge separation dynamics in a narrow band gap polymer-PbS nanocrystal blend for efficient hybrid solar cells
- 2012
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Ingår i: Journal of Materials Chemistry. - : Royal Society of Chemistry (RSC). - 1364-5501 .- 0959-9428. ; 22:46, s. 24411-24416
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Tidskriftsartikel (refereegranskat)abstract
- We have demonstrated efficient hybrid solar cells based on lead sulfide (PbS) nanocrystals and a narrow band gap polymer, poly[{2,5-bis(2-hexyldecyl)-2,3,5,6-tetrahydro-3,6-dioxopyrrolo[3,4-c]py rrole-1,4-diyl}-alt-{[2,2'-(1,4-phenylene)bis-thiophene]-5,5'-diyl}], (PDPPTPT). An opportune mixing of the two materials led to the formation of an energetically favorable bulk hetero-junction with a broad spectral response. Using a basic device structure, we reached a power conversion efficiency of similar to 3%, which is one of the highest values reported for this class of solar cells. Photo-physical measurements carried out on the device provided insights into the working mechanism: the comparison between the time decay of the pristine polymer and the polymer PbS blend allows us to conclude that efficient charge transfer is taking place in this hybrid system.
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30. |
- Cannizzaro, G., et al.
(författare)
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Machined versus roughened immediately loaded and finally restored single implants inserted flapless: Preliminary 6-month data from a split-mouth randomised controlled trial
- 2016
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Ingår i: European Journal of Oral Implantology. - 1756-2406. ; 9:2, s. 155-163
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To compare the outcome of immediately loaded single implants with a machined or a roughened surface. Materials and methods: Fifty patients had two implant sites randomly allocated to receive flapless-placed single Syra implants (Sweden & Martina), one with a machined and one with a roughened surface (sand-blasted with zirconia powder and acid etched), according to a split-mouth design. To be loaded immediately, implants had to be inserted with a torque superior to 50 Ncm. Implants were restored with definitive crowns in direct occlusal contact within 48 h. Patients were followed for 6 months after loading. Outcome measures were prosthetic and implant failures and complications. Results: Two machined implants and four roughened implants were not loaded immediately. Six months after loading no dropout occurred. One implant loaded late, which had a rough implant surface, failed 20 days after loading (P (McNemar test) = 0.625; difference in proportions = -0.04; 95% CI: -0.15 to 0.07). Three crowns had to be remade on machined implants and four on roughened implants (P (McNemar test) = 1.000; difference in proportions = -0.02; 95% CI: -0.12 to 0.08). Three machined and five roughened implants experienced complications (P (McNemar test) = 0.625; difference in proportions = -0.04; 95% CI: -0.15 to 0.07). There were no statistically significant differences between groups for crown and implant losses as well as complications. Conclusions: Up to 6 months after loading both machined and roughened flapless-placed and immediately loaded single implants provided good and similar results, however, longer follow-ups are needed to evaluate the long-term prognosis of implants with different surfaces.
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- Thompson, J. J.P., et al.
(författare)
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Phonon-Bottleneck Enhanced Exciton Emission in 2D Perovskites
- 2024
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Ingår i: Advanced Energy Materials. - 1614-6840 .- 1614-6832. ; 14:20
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Tidskriftsartikel (refereegranskat)abstract
- Layered halide perovskites exhibit remarkable optoelectronic properties and technological promise, driven by strongly bound excitons. The interplay of spin-orbit and exchange coupling creates a rich excitonic landscape, determining their optical signatures and exciton dynamics. Despite the dark excitonic ground state, surprisingly efficient emission from higher-energy bright states has puzzled the scientific community, sparking debates on relaxation mechanisms. Combining low-temperature magneto-optical measurements with sophisticated many-particle theory, the origin of the bright exciton emission in perovskites is elucidated by tracking the thermalization of dark and bright excitons under a magnetic field. The unexpectedly high emission is clearly attributed to a pronounced phonon-bottleneck effect, considerably slowing down the relaxation toward the energetically lowest dark states. It is demonstrated that this bottleneck can be tuned by manipulating the bright-dark energy splitting and optical phonon energies, offering valuable insights and strategies for controlling exciton emission in layered perovskite materials that is crucial for optoelectronics applications.
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- Abreu, Soraia Carvalho, et al.
(författare)
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Lung Inflammatory Environments Differentially Alter Mesenchymal Stromal Cell Behavior
- 2019
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Ingår i: American Journal of Physiology: Lung Cellular and Molecular Physiology. - : American Physiological Society. - 1522-1504 .- 1040-0605. ; 317:6, s. 823-831
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Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stromal (stem) cells (MSCs) are increasingly demonstrated to ameliorate experimentally-induced lung injuries through disease-specific anti-inflammatory actions, thus suggesting that different in vivo inflammatory environments can influence MSC actions. To determine the effects of different representative inflammatory lung conditions, human bone marrow-derived MSCs (hMSCs) were exposed to in vitro culture conditions from bronchoalveolar lavage fluid (BALF) samples obtained from patients with either the acute respiratory distress syndrome (ARDS) or with other lung diseases including acute respiratory exacerbations of cystic fibrosis (CF) (non-ARDS). hMSCs were subsequently assessed for time- and BALF concentration-dependent effects on mRNA expression of selected pro- and anti-inflammatory mediators, and for overall patterns of gene and mRNA expression. Both common and disease specific-patterns were observed in gene expression of different hMSC mediators, notably interleukin (IL)-6. Conditioned media obtained from non-ARDS BALF-exposed hMSCs was more effective in promoting an anti-inflammatory phenotype in monocytes than was conditioned media from ARDS BALF-exposed hMSCs. Neutralizing IL-6 in the conditioned media promoted generation of anti-inflammatory monocyte phenotype. These results demonstrated that different lung inflammatory environments differentially alter hMSC behavior. Further identification of these interactions and the driving mechanisms may influence clinical use of MSCs for treating lung diseases.
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- Cannizzaro, G., et al.
(författare)
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Immediate loading of two (fixed-on-2) versus three (fixed-on-3) implants placed flapless supporting cross-arch fixed prostheses: One-year results from a randomised controlled trial
- 2016
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Ingår i: European Journal of Oral Implantology. - 1756-2406. ; 9:2, s. 143-153
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate the outcome of two (fixed-on-2 = FO2) versus three (fixed-on-3 = FO3) implants placed flapless in fully edentulous jaws and immediately restored with metal-resin screw-retained crossarch prostheses. Materials and methods: Forty edentulous or to be rendered edentulous patients (20 in the maxilla and 20 in the mandible) were randomised to the FO2 group (20 patients: 10 in the maxilla and 10 in the mandible) and to the FO3 group (20 patients: 10 in the maxilla and 10 in the mandible) according to a parallel group design. To be immediately loaded, implants had to be inserted with a minimum torque of 60 Ncm. Outcome measures were prosthesis and implant failures, complications and peri-implant marginal bone level changes evaluated up to 1-year post-loading. Results: Flaps were raised in four patients and two prostheses were loaded early at 8 weeks in the FO2 group. One year after loading no dropout or implant failure occurred, however one FO2 maxillary prosthesis had to be remade because of repeated screw-loosening (risk difference = 0.05; 95% CI: -0.05 to 0.15; Fisher's exact test P = 1.000). Three FO2 patients were affected by complications versus five FO3 patients (risk difference = -0.1; 95% CI: -0.35 to 0.15; Fisher's exact test; P = 0.695). There were no statistically significant differences for prosthetic failures and complications between groups. There were no statistically significant differences for marginal peri-implant bone levels between the two groups (estimate of the difference = 0.031 mm; 95% Cl: -0.22 to 0.28; P (ancova) = 0.803), with both groups losing marginal bone in a statistically significant way (0.27 mm for FO2 patients and 0.24 mm for FO3 patients). Conclusions: These preliminary results suggest that immediately loaded cross-arch prostheses can be supported by only two or three dental implants at least up to 1-year post-loading. Longer follow-ups are needed to properly evaluate both these therapeutic options.
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- Fantuzzi, Andrea, et al.
(författare)
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Bicarbonate activation of the monomeric photosystem II-PsbS/Psb27 complex
- 2023
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Ingår i: Plant Physiology. - : Oxford University Press. - 0032-0889 .- 1532-2548. ; 192:4, s. 2656-2671
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Tidskriftsartikel (refereegranskat)abstract
- In thylakoid membranes, photosystem II (PSII) monomers from the stromal lamellae contain the subunits PsbS and Psb27 (PSIIm-S/27), while PSII monomers (PSIIm) from granal regions lack these subunits. Here, we have isolated and characterized these 2 types of PSII complexes in tobacco (Nicotiana tabacum). PSIIm-S/27 showed enhanced fluorescence, the near absence of oxygen evolution, and limited and slow electron transfer from QA to QB compared to the near-normal activities in the granal PSIIm. However, when bicarbonate was added to PSIIm-S/27, water splitting and QA to QB electron transfer rates were comparable to those in granal PSIIm. The findings suggest that the binding of PsbS and/or Psb27 inhibits forward electron transfer and lowers the binding affinity for bicarbonate. This can be rationalized in terms of the recently discovered photoprotection role played by bicarbonate binding via the redox tuning of the QA/QA•- couple, which controls the charge recombination route, and this limits chlorophyll triplet-mediated 1O2 formation. These findings suggest that PSIIm-S/27 is an intermediate in the assembly of PSII in which PsbS and/or Psb27 restrict PSII activity while in transit using a bicarbonate-mediated switch and protective mechanism.
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- Zardavas, Dimitrios, et al.
(författare)
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Tumor PIK3CA Genotype and Prognosis in Early-Stage Breast Cancer: A Pooled Analysis of Individual Patient Data
- 2018
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Ingår i: Journal of Clinical Oncology. - : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 36:10, s. 981-
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Tidskriftsartikel (refereegranskat)abstract
- PurposePhosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations are frequently observed in primary breast cancer. We evaluated their prognostic relevance by performing a pooled analysis of individual patient data.Patients and MethodsAssociations between PIK3CA status and clinicopathologic characteristics were tested by applying Cox regression models adjusted for age, tumor size, nodes, grade, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, treatment, and study. Invasive disease-free survival (IDFS) was the primary end point; distant disease-free survival (DDFS) and overall survival (OS) were also assessed, overall and by breast cancer subtypes.ResultsData from 10,319 patients from 19 studies were included (median OS follow-up, 6.9 years); 1,787 patients (17%) received chemotherapy, 4,036 (39%) received endocrine monotherapy, 3,583 (35%) received both, and 913 (9%) received none or their treatment was unknown. PIK3CA mutations occurred in 32% of patients, with significant associations with ER positivity, increasing age, lower grade, and smaller size (all P amp;lt; .001). Prevalence of PIK3CA mutations was 18%, 22%, and 37% in the ER-negative/HER2-negative, HER2-positive, and ER-positive/HER2-negative subtypes, respectively. In univariable analysis, PIK3CA mutations were associated with better IDFS (HR, 0.77; 95% CI, 0.71 to 0.84; P amp;lt; .001), with evidence for a stronger effect in the first years of follow-up (0 to 5 years: HR, 0.73; 95% CI, 0.66 to 0.81; P amp;lt; .001; 5 to 10 years: HR, 0.82; 95% CI, 0.68 to 0.99; P = .037); amp;gt; 10 years: (HR, 1.15; 95% CI, 0.84 to 1.58; P = .38; P heterogeneity = .02). In multivariable analysis, PIK3CA genotype remained significant for improved IDFS (P = .043), but not for the DDFS and OS end points.ConclusionIn this large pooled analysis, PIK3CA mutations were significantly associated with a better IDFS, DDFS, and OS, but had a lesser prognostic effect after adjustment for other prognostic factors. (C) 2018 by American Society of Clinical Oncology
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