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| 2. |
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| 3. |
- Abrahamsson, Mattias, et al.
(author)
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Ämnesprovet i NO : biologi, fysik och kemi
- 2013
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In: Ämnesproven 2012 i grundskolans årskurs 9 och specialskolans årskurs 10. - Stockholm : Skolverket. - 9789175590233 ; , s. 32-44
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Book chapter (other academic/artistic)
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| 7. |
- Bergqvist, Ove, et al.
(author)
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Analys av flyktingfrågan – vad är det vi vill att eleverna ska kunna göra när de analyserar flyktingsituationen, och vad i vår undervisning möjliggör det?
- 2017
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In: Lärarnas forskningskonferens 31 oktober 2017. ; , s. 24-25
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Conference paper (other academic/artistic)abstract
- I samhällskunskap undervisas elever i frågor om hur olika samhällen är organiserade och strukturerade, om värden och värdefrågor samt om hur man kan analysera, kritiskt granska och dra relevanta slutsatser om argument i samhällsfrågor. Undervisningen utgår ofta från de dagsaktuella frågor som på- verkar vårt samhälle just nu. En av dessa samhällsfrågor är det faktum att många människor under en längre tid flytt i båt över Medelhavet, en farofylld flykt som medför stora risker och en osäker framtid. Projektets utgångspunkt är denna aktuella flyktingsituation - varför så många flyr, varför andra stannar kvar och hur individer och samhälle påverkas av flyktingsituationen, idag och i den nära framtiden. Vad är det man kan när man kan analysera flyktingsituationen – om man går i ettan, i sexan, i åttan, eller första året på gymnasiet? Hur kan vi undervisa kring detta i samhällskunskap för att utveckla elevernas förmåga att analysera flyktingsituationen? Det här är ett aktuellt och viktigt ämnesområde, och kunnandet som undersöks (förmågan att analysera en samhällsfråga) är grundläggande för samhällskunskap. Samtidigt saknas nästan helt svensk forskning om elevers lärande i interaktion med läraren i undervisning på området (Olsson, 2016, s. 71). Internationell forskning har främst fokuserat hur elevers idéer om samhällsfrågor relaterar till social bakgrund och kulturell identitet (Barton & Avery, 2016), medan forskning som syftar till att beskriva innebörden av elevers samhällskunskapskunnande saknas. I ett större ram-projekt som påbörjades 2015 av SO-nätverket inom Stockholm Teaching & Learning Studies undersöks elevers förmåga att analysera i ämnet samhällskunskap. Syftet med ramprojektet är att bidra till att elevers analysförmåga preciseras och att vi på så vis utvecklar kunskap om hur denna förmåga kan möjliggöras genom undervisning. Symposiet presenterar tre delprojekt som inom ramen för den övergripande studien om innebörden av analysförmågan i samhällskunskap undersöker innebörden av och undervisning för elevers förmåga att analysera situationen med flyktingströmmarna från Syrien till Europa. Tre lärarlag från olika undervisningsstadier – låg- och mellanstadiet, högstadiet och gymnasiet – har under läsåret 2016/2017 utformat och studerat undervisning för elever i årskurs 1 och 6, i årskurs 8 och i gymnasiets år 1. I delprojekten har elevers erfarande av flyktingsituationen och deras sätt att analysera denna kartlagts och analyserats fenomenografiskt (Marton, 1981; Larsson, 1986). Lärargrupperna har därefter utgått från resultaten av dessa kartläggningsanalyser för att med hjälp av variationsteori (Lo, 2012; Marton, 2014) utforma, pröva och revidera undervisning för att möjliggöra elevers utvecklande av förmågan att analysera flyktingsituationen. Varje delstudie har genomfört två cykler av planering, genomförande och analys av forskningslektioner med åtföljande för- och eftertest (jfr. Learning Study). Elevmaterial i form av skriftliga kartläggningar och inspelade och transkriberade lektioner/ gruppdiskussioner har analyserats för att identifiera kritiska aspekter (Marton 2014; Pang & Ki, 2016) av förmågan att analysera flyktingsituationen som behöver fokuseras i undervisning. Under symposiet presenteras de gemensamma utgångspunkterna och frågeställningarna, samt de tre delprojektens olika undervisningsinterventioner och analyser. Sammanfattningsvis diskuteras vilka likheter och skillnader som tycks finnas mellan olika skolstadier när det gäller att kunna analysera frågan om flyktingströmmarna över Medelhavet och kritiska aspekter av att kunna göra detta i olika undervisningskontexter.
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| 9. |
- Gabrielson, Marike, et al.
(author)
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Baseline breast tissue characteristics determine the effect of tamoxifen on mammographic density change
- 2024
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215.
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Journal article (peer-reviewed)abstract
- Tamoxifen prevents recurrence of breast cancer and is also approved for preventive, risk-reducing, therapy. Tamoxifen alters the breast tissue composition and decreases the mammographic density. We aimed to test if baseline breast tissue composition influences tamoxifen-associated density change. This biopsy-based study included 83 participants randomised to 6 months daily intake of placebo, 20, 10, 5, 2.5, or 1 mg tamoxifen. The study is nested within the double-blinded tamoxifen dose-determination trial Karolinska Mammography Project for Risk Prediction of Breast Cancer Intervention (KARISMA) Study. Ultrasound-guided core-needle breast biopsies were collected at baseline before starting treatment. Biopsies were quantified for epithelial, stromal, and adipose distributions, and epithelial and stromal expression of proliferation marker Ki67, oestrogen receptor (ER) and progesterone receptor (PR). Mammographic density was measured using STRATUS. We found that greater mammographic density at baseline was positively associated with stromal area and inversely associated with adipose area and stromal expression of ER. Premenopausal women had greater mammographic density and epithelial tissue, and expressed more epithelial Ki67, PR, and stromal PR, compared to postmenopausal women. In women treated with tamoxifen (1–20 mg), greater density decrease was associated with higher baseline density, epithelial Ki67, and stromal PR. Women who responded to tamoxifen with a density decrease had on average 17% higher baseline density and a 2.2-fold higher PR expression compared to non-responders. Our results indicate that features in the normal breast tissue before tamoxifen exposure influences the tamoxifen-associated density decrease, and that the age-associated difference in density change may be related to age-dependant differences in expression of Ki67 and PR.
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| 10. |
- Gabrielson, Marike, et al.
(author)
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Effects of tamoxifen on normal breast tissue histological composition : Results from a randomised six-arm placebo-controlled trial in healthy women
- 2023
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 152:11, s. 2362-2372
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Journal article (peer-reviewed)abstract
- Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.
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| 11. |
- Hammarström, Mattias, et al.
(author)
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Side effects of low-dose tamoxifen : results from a six-armed randomised controlled trial in healthy women
- 2023
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In: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 129:1, s. 61-71
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Journal article (peer-reviewed)abstract
- Background: Adherence to adjuvant tamoxifen therapy is suboptimal, and acceptance of tamoxifen for primary prevention is poor. Published results indicate effect of low-dose tamoxifen therapy. Using questionnaire data from a randomised controlled trial, we describe side effects of standard and low-dose tamoxifen in healthy women. Methods: In the KARISMA trial, 1440 healthy women were randomised to 6 months of daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. Participants completed a 48-item, five-graded Likert score symptom questionnaire at baseline and follow-up. Linear regression models were used to identify significant changes in severity levels across doses and by menopausal status. Results: Out of 48 predefined symptoms, five were associated with tamoxifen exposure (hot flashes, night sweats, cold sweats, vaginal discharge and muscle cramps). When comparing these side effects in premenopausal women randomised to low doses (2.5, 5 mg) versus high doses (10, 20 mg), the mean change was 34% lower in the low-dose group. No dose-dependent difference was seen in postmenopausal women. Conclusions: Symptoms related to tamoxifen therapy are influenced by menopausal status. Low-dose tamoxifen, in contrast to high-dose, was associated with less pronounced side effects, a finding restricted to premenopausal women. Our findings give new insights which may influence future dosing strategies of tamoxifen in both the adjuvant and preventive settings. Trial registration: ClinicalTrials.gov ID: NCT03346200.
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| 12. |
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| 13. |
- Hedman, Mattias, et al.
(author)
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Fractionated Irradiation of Five Human Lung Cancer Cell Lines and Prediction of Survival According to a Radiobiology Model
- 2011
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 31:4, s. 1125-1130
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Journal article (peer-reviewed)abstract
- Background: This study evaluates a predictive radiobiology model by measurements of surviving fraction (SF) by the clonogenic assay or the extrapolation method and the proliferation rate in vitro. It is hypothesized that incorporating proliferation to intrinsic radiosensitivity, measured by SF, to predict radiation responsiveness after fractionated irradiation adds to the model's accuracy. Materials and Methods. Five lung cancer cell lines with known SF after 1 Gy (SF1), and also SF2 and SF5, were irradiated with three different fractionation regimes; 10x1 Gy, 5x2 Gy or 2x5 Gy during the same total time to achieve empirical SF. In addition, the SF1, SF2 and SF5 after fractionated irradiation was calculated for each cell line based on the already known single fraction SF and with or without a proliferation factor. The results were compared to the empirical data. Results and Discussion: By using the clonogenic assay to measure radiosensitivity, prediction of radiosensitivity was improved after fractionated radiotherapy when proliferation was used in the radiobiology model. However, this was not the case in the cell lines where the extrapolation method was used to calculate SF. Thus, a radiobiology model including intrinsic radiosensitivity, measured by the clonogenic assay, as well as proliferation, is better at predicting survival after fractionated radiotherapy, compared to the use of intrinsic radiosensitivity alone.
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| 14. |
- Jägerskog, Ann-Sofie, 1977-, et al.
(author)
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Varför fortsätter flykten över Medelhavet? : Innebörden av att göra en kausalanalys av en samhällsfråga
- 2021
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In: Forskning om undervisning och lärande. - 2000-9674 .- 2001-6131. ; 9:2, s. 5-29
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Journal article (peer-reviewed)abstract
- Denna artikel bygger på en studie som undersöker vad det innebär att analysera ensamhällsfråga i samhällskunskap, en viktig del av kritiskt tänkande, och vad eleverbehöver erfara i undervisningen för att utveckla en mer kvalificerad analysförmåga.Elever från samtliga stadier i grundskolan ombads att, före och efter en lektion somfokuserade på flyktingsituationen kring Medelhavet, skriftligt besvara en fråga omorsaker till denna flykt. En fenomenografisk analys av de 233 elevsvar som genererades visade att det sätt som eleverna erfor flyktingsituationen på var tydligt kopplat tillkvalitén på deras analyser. I analysen av elevsvaren identifierades tre aspekter somtycks vara kritiska för elever att urskilja för att de ska kunna kvalificera sina kausalanalyser av en samhällsfråga. Dessa aspekter berör en samhällsfrågas dynamik,komplexiteten i kausalitet och vikten av att ta olika dimensioner i beaktande (somsamhälleliga respektive individuella dimensioner eller historiska respektive framtidadimensioner). Dessa aspekter visade sig var viktiga för elever i alla årskurser somingick i studien. Artikeln diskuterar även implikationer för undervisning.
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| 15. |
- Larsson, Anna Maria, et al.
(author)
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Serial evaluation of serum thymidine kinase activity is prognostic in women with newly diagnosed metastatic breast cancer
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10
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Journal article (peer-reviewed)abstract
- The rapid development of new therapies in metastatic breast cancer (MBC), entails a need for improved prognostic and monitoring tools. Thymidine kinase 1 (TK1) is involved in DNA synthesis and its activity correlates to outcome in cancer patients. The aim of this study was to evaluate serum TK1 activity (sTK1) levels in MBC patients as a tool for prognostication and treatment monitoring. 142 women with MBC scheduled for 1st line systemic treatment were included in a prospective observational study. sTK1 was measured at baseline (BL) and at 1, 3 and 6 months and correlations to progression-free and overall survival (PFS, OS) evaluated. High sTK1 levels (above median) correlated to worse PFS and OS at BL, also after adjusting for other prognostic factors. sTK1 levels were significantly associated with PFS and OS measured from follow-up time points during therapy. Changes from 3 to 6 months during therapy significantly correlated to PFS and OS, whereas early changes did not. We could demonstrate sTK1 level as an independent prognostic factor in patients with newly diagnosed MBC. Changes in sTK1 levels from 3 to 6 months correlated to PFS and OS. Future studies of sTK1 are warranted to further define its clinical utility.
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| 16. |
- Lorant, Camilla, et al.
(author)
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The risk factors associated with post-transplantation BKPyV nephropathy and BKPyV DNAemia : a prospective study in kidney transplant recipients
- 2024
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In: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 24
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Journal article (peer-reviewed)abstract
- Background: BK polyomavirus (BKPyV) infection after kidney transplantation can lead to serious complications such as BKPyV-associated nephropathy (BKPyVAN) and graft loss. The aim of this study was to investigate the incidence of BKPyVAN after implementing a BKPyV screening program, to map the distribution of BKPyV genotypes and subtypes in the Uppsala-orebro region and to identify host and viral risk factors for clinically significant events.Methods This single-center prospective cohort study included kidney transplant patients aged >= 18 years at the Uppsala University Hospital in Sweden between 2016 and 2018. BKPyV DNA was analyzed in plasma and urine every 3 months until 18 months after transplantation. Also genotype and subtype were determined. A logistic regression model was used to analyze selected risk factors including recipient sex and age, AB0 incompatibility and rejection treatment prior to BKPyVAN or high-level BKPyV DNAemia.Results: In total, 205 patients were included. Of these, 151 (73.7%) followed the screening protocol with 6 plasma samples, while184 (89.8%) were sampled at least 5 times. Ten (4.9%) patients developed biopsy confirmed BKPyVAN and 33 (16.1%) patients met criteria for high-level BKPyV DNAemia. Male sex (OR 2.85, p = 0.025) and age (OR 1.03 per year, p = 0.020) were identified as significant risk factors for developing BKPyVAN or high-level BKPyV DNAemia. BKPyVAN was associated with increased viral load at 3 months post transplantation (82,000 vs. < 400 copies/mL; p = 0.0029) and with transient, high-level DNAemia (n = 7 (27%); p < 0.0001). The most common genotypes were subtype Ib2 (n = 50 (65.8%)) and IVc2 (n = 20 (26.3%)).Conclusions: Male sex and increasing age are related to an increased risk of BKPyVAN or high-level BKPyV DNAemia. BKPyVAN is associated with transient, high-level DNAemia but no differences related to viral genotype were detected.
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| 17. |
- Lundin, Mattias, 1970-
(author)
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Students’ participation in the realization of school science activities
- 2007
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Doctoral thesis (other academic/artistic)abstract
- I denna avhandling visar jag hur elever och lärare genomför NO-verksamhet i grundskolan. Avhandlingen illustrerar hur elevers frågor och uttryckta erfarenheter blir en del av ett etablerat ämnesinnehåll. Syftet med studien är att skapa förståelse för hur två agendor – varav den ena baseras på elevers deltagande och den andra baseras på ett etablerat ämnesinnehåll – orkestreras så att båda agendorna tillgodoses vid genomförandet av NO-verksamheten. Studien bygger på videoobservationer under NOlektioner i skolår 5-9. Analysen visar hur olika aktiviteter i genomförandet av ett NOprojekt orkestrerar elevers frågor och uttryckta erfarenheter med ett naturvetenskapligt innehåll. Analysen visar också hur naturvetenskapens karaktär, the Nature of Science (NOS), kommuniceras som följemening till instruktioner. Vidare illustrerar avhandlingen olika sätt att använda frågor för att överbrygga vetenskapliga och vardagliga sätt att kommunicera. Resultaten visar också olika roller som elevers erfarenheter antar i en NOverksamhet. Resultaten utgör en konkretisering av skolans naturvetenskap, the Nature of School Science (NOSS). Skolans naturvetenskapliga aktiviteter begripliggörs lämpligen om de betraktas utifrån sina egna syften och förutsättningar. I avhandlingen utvecklas begreppet NOSS för att lyfta fram sådana syften och förutsättningar såsom dessa framträder i aktiviteten.
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| 18. |
- Reizenstein, Johan A, et al.
(author)
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Time trends in T3 to T4 laryngeal cancer : a population-based long-term analysis.
- 2014
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In: Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 36:12
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Journal article (peer-reviewed)abstract
- BACKGROUND: A decline in laryngectomies and survival in laryngeal cancer has been reported, especially among patients with advanced tumors.METHODS: Of 1058 patients with laryngeal cancer diagnosed from 1978 to 2007 in the Uppsala-Örebro region in Sweden, 263 T3 to T4 tumors treated with curative intent were studied retrospectively. Two time periods were defined, 1978 to 1992 and 1993 to 2007.RESULTS: Glottic tumors decreased constituting 68.6% of cases in 1978 to 1992 and 47.9% in 1993 to 2007. Laryngectomies were performed in 38.8% and 34.5% in the corresponding time periods. The use of laryngectomy was not strongly prognostic. A decline in overall survival (OS) over time could only be identified for the first year of follow-up. Chemotherapy was only used in a minority of cases.CONCLUSION: The marked decrease of glottic site may mark a shift in etiology. Laryngectomy was not strongly associated with improved survival. The absence of improved survival calls for intensified research.
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| 19. |
- Sah, Vasu R., et al.
(author)
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Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy
- 2023
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In: Cancer Research Communications. - : American Association For Cancer Research (AACR). - 2767-9764. ; 3:5, s. 884-895
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Journal article (peer-reviewed)abstract
- Purpose: Patients with metastatic uveal melanoma have limited therapeutic options and high mortality rate so new treatment options are needed.Patients and Methods: We previously reported that patients treated with the PD-1 inhibitor pembrolizumab and the histone deacetylase inhibitor entinostat in the PEMDAC trial, experienced clinical benefits if their tu-mor originated from iris or was wildtype for BAP1 tumor suppressor gene. Here we present the 2-year follow-up of the patients in the PEMDAC trial and identify additional factors that correlate with response or survival.Results: Durable responses were observed in 4 patients, with additional 8 patients exhibiting a stable disease. The median overall survival was 13.7 months. Grade 3 adverse events were reported in 62% of the patients, but they were all manageable. No fatal toxicity was observed. Activity of thymidine kinase 1 in plasma was higher in patients with stable disease or who progressed on treatment, compared with those with partial response. Chemokines and cytokines were analyzed in plasma. Three chemokines were significantly different when comparing patients with and without response. One of the factors, CCL21, was higher in the plasma of respond-ing patients before treatment initiation but decreased in the same patients upon treatment. In tumors, CCL21 was expressed in areas resembling ter -tiar y lymphoid structures (TLS). High plasma levels of CCL21 and presence of TLS-like regions in the tumor correlated with longer survival.Conclusions: This study provides insight into durable responses in the PEMDAC trial, and describes dynamic changes of chemokines and cytokines in the blood of these patients.Significance: The most significant finding from the 2-year follow-up study of the PEMDAC trial was that high CCL21 levels in blood was associated with response and survival. CCL21 was also expressed in TLS-like regions and presence of these regions was associated with longer survival. These analyses of soluble and tumor markers can inform on predictive biomark-ers needing validation and become hypothesis generating for experimental research.
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| 20. |
- Strömgren, Mattias, et al.
(author)
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A process-oriented evaluation of nine accident investigation methods
- 2015
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In: Safety Science Monitor. - : IPSO AUSTRALIA. - 1443-8844. ; 19:1
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Journal article (peer-reviewed)abstract
- A range of methods for accident investigation have been published. They focus on different aspects and provide support in various respects to the entire investigation process. Previous research has examined strengths and weaknesses of methods in analytical terms, but few or none so far have studied their capability to support the accident investigation process. During a number of training courses on advanced accident investigation methodology, held annually at Karlstad University since 2003, systematic tests of nine accident investigation methods were performed. The methods' process supporting properties were qualitatively evaluated against a general model of the investigation process. The results show that none of the methods provide strong support for all steps of the investigation process. A few methods, including STEP and Deviation analysis, however, provide a relatively strong support for certain key elements of the process. Most methods are supportive to the analysis phase, but less supportive to the planning and concluding phases. This in turn implies that several methods should be termed accident analysis methods rather than accident investigation methods. The results also point to differences in analytical principles and output formats, which also affect their usefulness.
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| 21. |
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| 22. |
- Sädbom, Stefan, et al.
(author)
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The use of systematic sampling and XRF-XRT based scanning to determine potential recovery of metals from waste rock
- 2020
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In: Mine Water Solutions. - : International Mine Water Association. - 9783000672972 ; , s. 146-151
-
Conference paper (peer-reviewed)abstract
- It is difficult to evaluate the potential for reprocessing and extraction of minerals from waste rock with valuable and/or harmful elements.We suggest a new sampling strategy/protocol for waste rock, specifically developed for historic mining sites, in combination with XRF-XRT scanning with a GeoCore X10 instrument.Håkansboda historical mine site in Sweden was used as a case study to look at the potential for the combination of techniques.The combination of the suggested randomized sampling strategy/protocol and the dataset from the GX10 scanning enables prediction of amenability for pre-processing with the use of mechanical sorting or if the extraction of valuable minerals only can be achieved through fine grinding, flotation or leaching.
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| 23. |
- Tang, Zheng, et al.
(author)
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Semi-Transparent Tandem Organic Solar Cells with 90% Internal Quantum Efficiency
- 2012
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In: Advanced Energy Materials. - : Wiley. - 1614-6840 .- 1614-6832. ; 2:12, s. 1467-1476
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Journal article (peer-reviewed)abstract
- Semi-transparent (ST) organic solar cells with potential application as power generating windows are studied. The main challenge is to find proper transparent electrodes with desired electrical and optical properties. In this work, this is addressed by employing an amphiphilic conjugated polymer PFPA-1 modified ITO coated glass substrate as the ohmic electron-collecting cathode and PEDOT:PSS PH1000 as the hole-collecting anode. For active layers based on different donor polymers, considerably lower reflection and parasitic absorption are found in the ST solar cells as compared to solar cells in the standard geometry with an ITO/PEDOT:PSS anode and a LiF/Al cathode. The ST solar cells have remarkably high internal quantum efficiency at short circuit condition (similar to 90%) and high transmittance (similar to 50%). Hence, efficient ST tandem solar cells with enhanced power conversion efficiency (PCE) compared to a single ST solar cell can be constructed by connecting the stacked two ST sub-cells in parallel. The total loss of photons by reflection, parasitic absorption and transmission in the ST tandem solar cell can be smaller than the loss in a standard solar cell based on the same active materials. We demonstrate this by stacking five separately prepared ST cells on top of each other, to obtain a higher photocurrent than in an optimized standard solar cell.
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| 24. |
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| 25. |
- Zhu, Yajing, et al.
(author)
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The role of serum thymidine kinase 1 activity in neoadjuvant-treated HER2-positive breast cancer : biomarker analysis from the Swedish phase II randomized PREDIX HER2 trial
- 2024
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In: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 204:2, s. 299-308
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Journal article (peer-reviewed)abstract
- BackgroundThymidine kinase 1 (TK1) plays a pivotal role in DNA synthesis and cellular proliferation. TK1 has been studied as a prognostic marker and as an early indicator of treatment response in human epidermal growth factor 2 (HER2)-negative early and metastatic breast cancer (BC). However, the prognostic and predictive value of serial TK1 activity in HER2-positive BC remains unknown.MethodsIn the PREDIX HER2 trial, 197 HER2-positive BC patients were randomized to neoadjuvant trastuzumab, pertuzumab, and docetaxel (DPH) or trastuzumab emtansine (T-DM1), followed by surgery and adjuvant epirubicin and cyclophosphamide. Serum samples were prospectively collected from all participants at multiple timepoints: at baseline, after cycle 1, 2, 4, and 6, at end of adjuvant therapy, annually for a total period of 5 years and/or at the time of recurrence. The associations of sTK1 activity with baseline characteristics, pathologic complete response (pCR), event-free survival (EFS), and disease-free survival (DFS) were evaluated.ResultsNo association was detected between baseline sTK1 levels and all the baseline clinicopathologic characteristics. An increase of TK1 activity from baseline to cycle 2 was seen in all cases. sTK1 level at baseline, after 2 and 4 cycles was not associated with pCR status. After a median follow-up of 58 months, 23 patients had EFS events. There was no significant effect between baseline or cycle 2 sTK1 activity and time to event. A non-significant trend was noted among patents with residual disease (non-pCR) and high sTK1 activity at the end of treatment visit, indicating a potentially worse long-term prognosis.ConclusionsTK1 activity increased following neoadjuvant therapy for HER2-positive BC but was not associated with patient outcomes or treatment benefit. However, the post-surgery prognostic value in patients that have not attained pCR warrants further investigation.Trial registrationClinicalTrials.gov, NCT02568839. Registered on 6 October 2015.
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