liu.seSearch for publications in DiVA
Change search
Refine search result
1 - 11 of 11
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Bill-Axelson, A.
    et al.
    Department of Urology, University Hospital, Uppsala, Sweden.
    Holmberg, L.
    Regional Oncologic Center, University Hospital, Uppsala, Sweden, King's College London, School of Medicine, Division of Cancer Studies, London, United Kingdom, Medical School, Division of Cancer Studies, Guy's Hospital, London SE1 9RT, United Kingdom.
    Filen, F.
    Filén, F., Department of Urology, University Hospital, Uppsala, Sweden.
    Ruutu, M.
    Department of Urology, Helsinki University Central Hospital, Helsinki, Finland.
    Garmo, H.
    Regional Oncologic Center, University Hospital, Uppsala, Sweden.
    Busch, C.
    Department of Pathology, University Hospital, Uppsala, Sweden.
    Nordling, S.
    Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland.
    Haggman, M.
    Häggman, M., Department of Urology, University Hospital, Uppsala, Sweden.
    Andersson, S.-O.
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Bratell, S.
    Department of Urology, Borås Hospital, Borås, Sweden.
    Spångberg, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Urology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Palmgren, J.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Adami, H.-O.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States.
    Johansson, J.-E.
    Department of Urology, Örebro University Hospital, Örebro, Sweden, Center for Assessment of Medical Technology, Örebro University Hospital, Örebro, Sweden.
    Radical prostatectomy versus watchful waiting in localized prostate cancer: The Scandinavian prostate cancer group-4 randomized trial2008In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 100, no 16, p. 1144-1154Article in journal (Refereed)
    Abstract [en]

    Background: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up. Methods: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided. Results: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P =. 09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94, P =. 03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88, P =. 006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8, P <. 001). Conclusion: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery. © The Author 2008. Published by Oxford University Press.

  • 2. Francis, Prudence
    et al.
    Crown, John
    Di Leo, Angelo
    Buyse, Marc
    Balil, Ana
    Andersson, Michael
    Nordenskjöld, Bo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Lang, Istvan
    Jakesz, Raimund
    Vorobiof, Daniel
    Gutiérrez, Jorge
    van Hazel, Guy
    Dolci, Stella
    Jamin, Sophie
    Bendahmane, Belguendouz
    Gelber, Richard D.
    Goldhirsch, Aron
    Castiglione-Gertsch, Monica
    Piccart-Gebhart, Martine
    Adjuvant chemotherapy with sequential or concurrent anthracycline and docetaxel: Breast International Group 02-98 randomized trial2008In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 100, no 2, p. 121-133Article in journal (Refereed)
    Abstract [en]

    Background: Docetaxel is more effective than doxorubicin for patients with advanced breast cancer. The Breast International Group 02-98 randomized trial tested the effect of incorporating docetaxel into anthracycline-based adjuvant chemotherapy and compared sequential vs concurrent administration of doxorubicin and docetaxel. Methods: Patients with lymph node-positive breast cancer (n = 2887) were randomly assigned to one of four treatments: 1) sequential control (four cycles of doxorubicin at 75 mg/m2, followed by three cycles of cyclophosphamide, methotrexate, and 5-fluorouracil [CMF]), 2) concurrent control (four cycles of doxorubicin at 60 mg/m2 plus cyclophosphamide at 600 mg/m2, followed by three cycles of CMF), 3) sequential docetaxel (three cycles of doxorubicin at 75 mg/m2, followed by three cycles of docetaxel at 100 mg/m2, followed by three cycles of CMF), 4) concurrent docetaxel (four cycles of doxorubicin at 50 mg/m2 plus docetaxel at 75 mg/m2, followed by three cycles of CMF). The primary comparison evaluated the efficacy of including docetaxel regardless of schedule and was planned after 1215 disease-free survival (DFS) events (ie, relapse, second primary cancer, or death from any cause). Docetaxel and control treatment groups were compared by log-rank tests, and hazard ratios (HR) of DFS events were calculated by Cox modeling. All statistical tests were two-sided. Results: Due to a lower-than-anticipated rate of relapse, this analysis was performed after 5 years with 732 events. Patients in control arms had a 5-year DFS of 73% (95% confidence interval [CI] = 70% to 75%). Docetaxel treatment resulted in an improvement in DFS of borderline statistical significance compared with control treatment (HR = 0.86, 95% CI = 0.74 to 1.00, P =. 05). However, DFS in the sequential docetaxel arm was better than that in the concurrent docetaxel arm (HR = 0.83, 95% CI = 0.69 to 1.00) and in the sequential control arm (HR = 0.79, 95% CI = 0.64 to 0.98). Conclusions: Incorporating docetaxel into anthracycline-based therapy resulted in an improvement in DFS that was of borderline statistical significance. However, important differences may be related to doxorubicin and docetaxel scheduling, with sequential but not concurrent administration, appearing to produce better DFS than anthracycline-based chemotherapy. © The Author(s).

  • 3. Holm, Caroline
    et al.
    Rayala, Suresh
    Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Huoston. TX.
    Jirström, Karin
    Stål, Olle
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Kumar, Rakesh
    Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Huoston. TX.
    Landberg, Göran
    Association between Pak1 expression and subcellular localization and tamoxifen resistance in breast cancer patients2006In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 98, no 10, p. 671-680Article in journal (Refereed)
    Abstract [en]

    Background: p21-activated kinase 1 (Pak1) phosphorylates many proteins in both normal and transformed cells. Its ability to phosphorylate and thereby activate the estrogen receptor α (ERα) potentially limits the effectiveness of antiestrogen treatment in breast cancer. Here we studied associations between Pak1 expression and subcellular localization in tumor cells and tamoxifen resistance.

    Methods: Pak1 protein expression was evaluated in 403 primary breast tumors from premenopausal patients who had been randomly assigned to 2 years of adjuvant tamoxifen or no treatment. Tamoxifen response was evaluated by comparing recurrence-free survival in relation to Pak1 and ERα expression in untreated versus tamoxifen-treated patients. Tamoxifen responsiveness of human MCF-7 breast cancer cells that inducibly expressed constitutively active Pak1 or that transiently overexpressed wild-type Pak1 (Wt-Pak1) or Pak1 that lacked functional nuclear localization signals (Pak1ΔNLS) was evaluated by analyzing cyclin D1 promoter activation and protein levels as markers for ERα activation. The response to tamoxifen in relation to Pak1 expression was analyzed in naturally tamoxifen-resistant Ishikawa human endometrial cancer cells. All statistical tests were two-sided.

    Results: Among patients who had ERα–positive tumors with low Pak1 expression, those treated with tamoxifen had better recurrence-free survival than those who received no treatment (hazard ratio [HR] = 0.502, 95% confidence interval [CI] = 0.331 to 0.762; P = .001) whereas there was no difference in recurrence-free survival between treatment groups for patients whose tumors had high cytoplasmic (HR = 0.893, 95% CI = 0.420 to 1.901; P = .769) or any nuclear Pak1 expression (HR = 0.955, 95% CI = 0.405 to 2.250; P = .916). In MCF-7 cells, overexpression of Wt-Pak1, but not of Pak1ΔNLS, compromised tamoxifen response by stimulating cyclin D1 expression. Treatment of Ishikawa cells with tamoxifen led to an increase in the amount of nuclear Pak1 and Pak1 kinase activity, suggesting that tamoxifen, to some extent, regulates Pak1 expression.

    Conclusions: Our data support a role for Pak1, particular Pak1 localized to the nucleus, in ERα signaling and in tamoxifen resistance.

  • 4. Holmberg, Lars
    et al.
    Iversen, Ole-Erik
    Rudenstam, Carl Magnus
    Hammar, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Kumpulainen, Eero
    Jaskiewicz, Janusz
    Dobaczewska, Daria
    Fjosne, Hans E
    Peralta, Octavio
    Arriagada, Rodrigo
    Holmqvist, Marit
    Maenpa, Johanna
    Increased risk of recurrence after hormone replacement therapy in breast cancer survivors2008In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 100, no 7, p. 475-482Article in journal (Refereed)
    Abstract [en]

    Background: Hormone replacement therapy (HT) is known to increase the risk of breast cancer in healthy women, but its effect on breast cancer risk in breast cancer survivors is less clear. The randomized HABITS study, which compared HT for menopausal symptoms with best management without hormones among women with previously treated breast cancer, was stopped early due to suspicions of an increased risk of new breast cancer events following HT. We present results after extended follow-up. Methods: HABITS was a randomized, non-placebo-controlled noninferiority trial that aimed to be at a power of 80% to detect a 36% increase in the hazard ratio (HR) for a new breast cancer event following HT. Cox models were used to estimate relative risks of a breast cancer event, the maximum likelihood method was used to calculate 95% confidence intervals (CIs), and χ2 tests were used to assess statistical significance, with all P values based on two-sided tests. The absolute risk of a new breast cancer event was estimated with the cumulative incidence function. Most patients who received HT were prescribed continuous combined or sequential estradiol hemihydrate and norethisterone. Results: Of the 447 women randomly assigned, 442 could be followed for a median of 4 years. Thirty-nine of the 221 women in the HT arm and 17 of the 221 women in the control arm experienced a new breast cancer event (HR = 2.4, 95% CI = 1.3 to 4.2). Cumulative incidences at 5 years were 22.2% in the HT arm and 8.0% in the control arm. By the end of follow-up, six women in the HT arm had died of breast cancer and six were alive with distant metastases. In the control arm, five women had died of breast cancer and four had metastatic breast cancer (P =. 51, log-rank test). Conclusion: After extended follow-up, there was a clinically and statistically significant increased risk of a new breast cancer event in survivors who took HT. © The Author 2008. Published by Oxford University Press.

  • 5. Jayson, Gordon
    et al.
    Zweit, Jamal
    Jackson, Alan
    Mulatero, Clive
    Julyan, Peter
    Ranson, Malcolm
    Broughton, Lynn
    Wagstaff, John
    Håkansson, Leif
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Groenewegen, Gerard
    Bailey, John
    Smith, Nigel
    Hastings, David
    Lawrence, Jeremy
    Haroon, Hamied
    Ward, Tim
    McGown, Alan
    Tang, Meina
    Levitt, Dan
    Marreaud, Sandrine
    Lehmann, Frederic
    Herold, Manfred
    Zwierzina, Heinz
    Molecular imaging and biological evaluation of HuMV833 anti-VEGF antibody: Implications for trial design of antiangiogenic antibodies2002In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 94, no 19, p. 1484-1493Article in journal (Refereed)
    Abstract [en]

    Background: Vascular endothelial growth factor (VEGF) is a potent angiogenic cytokine, and various inhibitory agents, including specific antibodies, have been developed to block VEGF-stimulated angiogenesis. We developed HuMV833, a humanized version of a mouse monoclonal anti-VEGF antibody (MV833) that has antitumor activity against a number of human tumor xenografts, and investigated the distribution and biologic effects of HuMV833 in patients in a phase I trial. Methods: Twenty patients with progressive solid tumors were treated with various doses of HuMV833 0.3, 1, 3, or 10 mg/kg). Positron emission tomography with 124I-HuMV833 was used to measure the antibody distribution in and clearance from tissues. Magnetic resonance imaging was used to measure the vascular permeability surface area product with a first-pass pharmacokinetic model (Kfp) to determine tumor vascular permeability. Results: The antibody was generally well tolerated, although the incremental dose, phase I study design, and pharmacodynamic end-points could not identify the optimum biologically active dose. Antibody distribution and clearance were markedly heterogeneous between and within patients and between and within individual tumor. HuMV833 distribution to normal tissues also varied among patients, but the antibody was cleared from these tissues in a homogeneous fashion. Permeability was strongly heterogeneous between and within patients and between and within individual tumors. All tumors showed a reduction in kfp 48 hours after the first treatment (median = 44%, range = 4%-91%). Conclusions: Because of the heterogeneity in tumor biology with respect to anti-body uptake and clearance, we suggest that either intrapatient dose escalation approaches or larger, more precisely defined patient cohorts would be preferable to conventional strategies in the design of phase I studies with anitiangiogenic compounds like HuMV833.

  • 6.
    Jung, Seungyoun
    et al.
    Harvard University, MA USA .
    Spiegelman, Donna
    Harvard University, MA USA .
    Baglietto, Laura
    Cancer Council Victoria, Australia .
    Bernstein, Leslie
    City Hope National Medical Centre, CA USA .
    Boggs, Deborah A.
    Boston University, MA USA .
    van den Brandt, Piet A.
    Maastricht University, Netherlands .
    Buring, Julie E.
    Harvard University, MA USA .
    Cerhan, James R.
    Mayo Clin, MN USA .
    Gaudet, Mia M.
    Amer Cancer Soc, GA USA .
    Giles, Graham G.
    Cancer Council Victoria, Australia .
    Goodman, Gary
    Fred Hutchinson Cancer Research Centre, WA USA .
    Hakansson, Niclas
    Karolinska Institute, Sweden .
    Hankinson, Susan E.
    Harvard University, MA USA .
    Helzlsouer, Kathy
    St Johns Mercy Medical Centre, MD USA .
    Horn-Ross, Pamela L.
    Cancer Prevent Institute Calif, CA USA .
    Inoue, Manami
    National Cancer Centre, Japan .
    Krogh, Vittorio
    Fdn IRCCS Ist Nazl Tumori Milano, Italy .
    Löf, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Nutrition. Linköping University, Faculty of Health Sciences.
    McCullough, Marjorie L.
    Amer Cancer Soc, GA USA .
    Miller, Anthony B.
    University of Toronto, Canada .
    Neuhouser, Marian L.
    Fred Hutchinson Cancer Research Centre, WA USA .
    Palmer, Julie R.
    Boston University, MA USA .
    Park, Yikyung
    NCI, MD USA .
    Robien, Kim
    University of Minnesota, MN USA .
    Rohan, Thomas E.
    Albert Einstein Coll Med, NY USA .
    Scarmo, Stephanie
    NYU, NY 10016 USA .
    Schairer, Catherine
    NCI, MD USA .
    Schouten, Leo J.
    Maastricht University, Netherlands .
    Shikany, James M.
    University of Alabama Birmingham, AL USA .
    Sieri, Sabina
    Fdn IRCCS Ist Nazl Tumori Milano, Italy .
    Tsugane, Schoichiro
    National Cancer Centre, Japan .
    Visvanathan, Kala
    Johns Hopkins Bloomberg School Public Heatlh, MD USA .
    Weiderpass, Elisabete
    Karolinska Institute, Sweden .
    Willett, Walter C.
    Harvard University, MA USA .
    Wolk, Alicja
    Karolinska Institute, Sweden .
    Zeleniuch-Jacquotte, Anne
    NYU, NY USA .
    Zhang, Shumin M.
    Brigham and Womens Hospital, MA USA .
    Zhang, Xuehong
    Brigham and Womens Hospital, MA USA .
    Ziegler, Regina G.
    NCI, MD USA .
    Smith-Warner, Stephanie A:
    Harvard University, MA USA .
    Fruit and Vegetable Intake and Risk of Breast Cancer by Hormone Receptor Status2013In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 105, no 3, p. 219-236Article in journal (Refereed)
    Abstract [en]

    Estrogen receptornegative (ER) breast cancer has few known or modifiable risk factors. Because ER tumors account for only 15% to 20% of breast cancers, large pooled analyses are necessary to evaluate precisely the suspected inverse association between fruit and vegetable intake and risk of ER breast cancer. less thanbrgreater than less thanbrgreater thanAmong 993 466 women followed for 11 to 20 years in 20 cohort studies, we documented 19 869 estrogen receptor positive (ER) and 4821 ER breast cancers. We calculated study-specific multivariable relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression analyses and then combined them using a random-effects model. All statistical tests were two-sided. less thanbrgreater than less thanbrgreater thanTotal fruit and vegetable intake was statistically significantly inversely associated with risk of ER breast cancer but not with risk of breast cancer overall or of ER tumors. The inverse association for ER tumors was observed primarily for vegetable consumption. The pooled relative risks comparing the highest vs lowest quintile of total vegetable consumption were 0.82 (95% CI 0.74 to 0.90) for ER breast cancer and 1.04 (95% CI 0.97 to 1.11) for ER breast cancer (Pcommon-effects by ER status andlt; .001). Total fruit consumption was non-statistically significantly associated with risk of ER breast cancer (pooled multivariable RR comparing the highest vs lowest quintile 0.94, 95% CI 0.85 to 1.04). less thanbrgreater than less thanbrgreater thanWe observed no association between total fruit and vegetable intake and risk of overall breast cancer. However, vegetable consumption was inversely associated with risk of ER breast cancer in our large pooled analyses.

  • 7.
    Kok, Marleen
    et al.
    Netherlands Canc Inst, Dept Expt Therapy, Amsterdam, Netherlands.
    Holm-Wigerup, Caroline
    Lund Univ, Malmo Univ Hosp, Ctr Mol Pathol, Malmo, Sweden.
    Hauptmann, Michael
    Netherlands Canc Inst, Dept Bioinformat and Stat, Amsterdam, Netherlands.
    Michalides, Rob
    Netherlands Canc Inst, Dept Tumor Biol, Amsterdam, Netherlands.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Linn, Sabine
    Netherlands Canc Inst, Dept Mol Biol, Amsterdam, Netherlands.
    Landberg, Goran
    Univ Manchester, Breakthrough Breast Canc Res Unit, Sch Canc Enabling Sci and Technol,Christie NHS Fdn, Manchester Acad Hlth Sci Ctr,Paterson Inst Canc R, Manchester M20 4BX, Lancs, England.
    Estrogen Receptor-alpha Phosphorylation at Serine-118 and Tamoxifen Response in Breast Cancer2009In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 101, no 24, p. 1725-1729Article in journal (Refereed)
    Abstract [en]

    Although estrogen receptor-alpha (ER alpha) is a marker used to identify breast cancer patients most likely to benefit from endocrine therapy, approximately 50% of ER alpha-positive breast carcinomas are resistant to tamoxifen. Preclinical studies have shown that phosphorylation of ER alpha at serine-118 (ER alpha S118-P) is required for tamoxifen-mediated inhibition of ER alpha-induced gene expression. We evaluated the association between recurrence-free survival after tamoxifen treatment and ER alpha S118-P expression by use of Cox proportional hazards regression. Data were from 239 premenopausal patients with breast cancer who participated in a randomized trial of 2 years of adjuvant tamoxifen treatment vs no systemic treatment. ER alpha S118-P expression was assessed by immunohistochemistry and categorized by use of the Allred score (low expression = score of 0-6; high expression = score of 7-8). All statistical tests were two-sided. Compared with systemically untreated patients, we found evidence of a benefit from adjuvant tamoxifen among patients whose tumors had high ER alpha S118-P expression (23.7 recurrences per 1000 person-years versus 72.2 recurrences per 1000 person-years, hazard ratio [HR] of recurrence = 0.36, 95% confidence interval [CI] = 0.20 to 0.65) but not among patients whose tumors had low expression (51.0 recurrences per 1000 person-years versus 57.0 recurrences per 1000 person-years, HR of recurrence = 0.87, 95% CI = 0.51 to 1.48.

  • 8.
    Lindstrom, Linda S.
    et al.
    Karolinska Inst, Sweden.
    Yau, Christina
    Univ Calif San Francisco, CA USA; Buck Inst Res Aging, CA USA.
    Czene, Kamila
    Karolinska Inst, Sweden.
    Thompson, Carlie K.
    Univ Calif San Francisco, CA USA.
    Hoadley, Katherine A.
    Univ North Carolina Chapel Hill, NC USA.
    vant Veer, Laura J.
    Univ Calif San Francisco, CA 94140 USA; Univ Calif San Francisco, CA 94143 USA.
    Balassanian, Ron
    Univ Calif San Francisco, CA 94140 USA.
    Bishop, John W.
    Univ Calif Davis, CA 95616 USA.
    Carpenter, Philip M.
    Univ Southern Calif, CA USA; Univ Calif Irvine, CA USA.
    Chen, Yunn-Yi
    Univ Calif San Francisco, CA 94140 USA.
    Datnow, Brian
    Univ Calif San Diego, CA 92093 USA.
    Hasteh, Farnaz
    Univ Calif San Diego, CA 92093 USA.
    Krings, Gregor
    Univ Calif San Francisco, CA 94140 USA.
    Lin, Fritz
    Univ Calif Irvine, CA USA.
    Zhang, Yanhong
    Univ Calif Davis, CA 95616 USA.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Benz, Christopher C.
    Univ Calif San Francisco, CA USA; Buck Inst Res Aging, CA USA.
    Fornander, Tommy
    Karolinska Inst, Sweden.
    Borowsky, Alexander D.
    Univ Calif Davis, CA 95616 USA.
    Esserman, Laura J.
    Univ Calif San Francisco, CA USA.
    Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer2018In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 110, no 7, p. 726-733, article id djx270Article in journal (Refereed)
    Abstract [en]

    Background: Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. Methods: The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Raos quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results: A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P amp;lt; .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio (HR] = 1.98, 95% confidence interval (CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI -1.18 to 4.99). Conclusions: Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors.

  • 9.
    Ma, Ran
    et al.
    Karolinska Institute, Sweden.
    Karthik, Govindasamy-Muralidharan
    Karolinska Institute, Sweden.
    Lovrot, John
    Karolinska Institute, Sweden.
    Haglund, Felix
    Karolinska Institute, Sweden; Karolinska University of Lab, Sweden.
    Rosin, Gustaf
    Karolinska Institute, Sweden.
    Katchy, Anne
    University of Houston, TX USA.
    Zhang, Xiaonan
    Karolinska Institute, Sweden.
    Viberg, Lisa
    Karolinska Institute, Sweden.
    Frisell, Jan
    Karolinska University Hospital, Sweden.
    Williams, Cecilia
    Karolinska Institute, Sweden; University of Houston, TX USA; Royal Institute Technology, Sweden.
    Linder, Stig
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Cancer Center Karolinska, Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden.
    Fredriksson, Irma
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Hartman, Johan
    Karolinska Institute, Sweden; Karolinska University of Lab, Sweden.
    Estrogen Receptor beta as a Therapeutic Target in Breast Cancer Stem Cells2017In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 109, no 3, article id djw236Article in journal (Refereed)
    Abstract [en]

    Background: Breast cancer cells with tumor-initiating capabilities (BSCs) are considered to maintain tumor growth and govern metastasis. Hence, targeting BSCs will be crucial to achieve successful treatment of breast cancer. Methods: We characterized mammospheres derived from more than 40 cancer patients and two breast cancer cell lines for the expression of estrogen receptors (ERs) and stem cell markers. Mammosphere formation and proliferation assays were performed on cells from 19 cancer patients and five healthy individuals after incubation with ER-subtype selective ligands. Transcriptional analysis was performed to identify pathways activated in ER beta-stimulated mammospheres and verified using in vitro experiments. Xenograft models (n = 4 or 5 per group) were used to study the role of ERs during tumorigenesis. Results: We identified an absence of ERa but upregulation of ER beta in BSCs associated with phenotypic stem cell markers and responsible for the proliferative role of estrogens. Knockdown of ER beta caused a reduction of mammosphere formation in cell lines and in patient-derived cancer cells (40.7%, 26.8%, and 39.1%, respectively). Gene set enrichment analysis identified glycolysis-related pathways (false discovery rate amp;lt; 0.001) upregulated in ER beta-activated mammospheres. We observed that tamoxifen or fulvestrant alone was insufficient to block proliferation of patient-derived BSCs while this could be accomplished by a selective inhibitor of ER beta (PHTPP; 53.7% in luminal and 45.5% in triple-negative breast cancers). Furthermore, PHTPP reduced tumor initiation in two patient-derived xenografts (75.9% and 59.1% reduction in tumor volume, respectively) and potentiated tamoxifen-mediated inhibition of tumor growth in MCF7 xenografts. Conclusion: We identify ER beta as a mediator of estrogen action in BSCs and a novel target for endocrine therapy.

  • 10.
    Nordenskjöld, Bo
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Rosell, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Rutqvist, Lars-Erik
    Department of Oncology, Södersjukhuset Hospital, Stockholm, Sweden.
    Malmström, Per-Olof
    Department of Oncology, Lund University Hospital, Lund, Sweden.
    Bergh, Jonas
    Department of Oncology, Karolinska Hospital, Stockholm, Sweden.
    Bengtsson, Nils-Olof
    Department of Oncology, Umeå University Hospital, Umeå, Sweden.
    Hatschek, Thomas
    Department of Oncology, Karolinska Hospital, Stockholm, Sweden.
    Wallgren, Arne
    Department of Oncology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Carstensen, John
    Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Department of Health and Society, Tema Health and Society.
    Coronary heart disease mortality after 5 years of adjuvant tamoxifen therapy: Results from a randomized trial2005In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 97, no 21, p. 1609-1610Article in journal (Refereed)
    Abstract [en]

    From January 1, 1983, through December 31, 1992, a total of 4610 patients entered a randomized trial that compared mortality among patients receiving 2 years of adjuvant tamoxifen therapy with that in patients receiving 5 years of adjuvant tamoxifen therapy, 4175 of whom were recurrence free after 2 years of tamoxifen therapy. Among the 2046 patients randomly assigned to the 5-year group all-cause mortality, breast cancer-specific mortality, and the incidence of contralateral breast cancer were reduced, compared with those among 2129 patients randomized in the 2-year group, but the incidence of endometrial cancer was increased. In addition, mortality from coronary heart disease was statistically significantly reduced in the 5-year group, compared with that in the 2-year group (hazard ratio = 0.67, 95% confidence interval = 0.47 to 0.94, P = .022 [two-sided Wald test]). Ten years after surgery, 2.1% of the patients in the 5-year group and 3.5% of those in the 2-year group had died from coronary heart disease. No statistically significant increases in mortality from other heart diseases, cerebrovascular diseases, or other vascular diseases were observed. © The Author 2005. Published by Oxford University Press. All rights reserved.

  • 11. Setlur, Sunita R.
    et al.
    Mertz, Kirsten D.
    Hoshida, yujin
    Demichelis, Francesca
    Lupien, Mathieu
    Perner, Sven
    Sboner, Andrea
    Pawitan, Yudi
    Andrén, Ove
    Johnson, Laura A.
    Tang, Jeff
    Adami, Hans-Olov
    Calza, Stefano
    Chinnaiyan, Arul M.
    Rhodes, Daniel
    Tomlins, Scott
    Fall, Katja
    Mucci, Lorelei A.
    Kantoff, Philip W.
    Stampfer, Meir J.
    Andersson, Swen-Olof
    Varenhorst, Eberhard
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Urology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Johansson, Jan-Erik
    Brown, Myles
    Golub, Todd R.
    Rubin, Mark A.
    Estrogen-dependent signaling in a molecularly distinct subclass of aggressive prostate cancer2008In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 100, no 11, p. 815-825Article in journal (Refereed)
    Abstract [en]

    Background: The majority of prostate cancers harbor gene fusions of the 5′-untranslated region of the androgen-regulated transmembrane protease serine 2 (TMPRSS2) promoter with erythroblast transformation-specific transcription factor family members. The common fusion between TMPRESS2 and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) is associated with a more aggressive clinical phenotype, implying the existence of a distinct subclass of prostate cancer defined by this fusion. Methods: We used complementary DNA-mediated annealing, selection, ligation, and extension to determine the expression profiles of 6144 transcriptionally informative genes in archived biopsy samples from 455 prostate cancer patients in the Swedish Watchful Waiting cohort (1987-1999) and the United States-based Physicians' Health Study cohort (1983-2003). A gene expression signature for prostate cancers with the TMPRSS2-ERG fusion was determined using partitioning and classification models and used in computational functional analysis. Cell proliferation and TMPRSS2-ERG expression in androgen receptor-negative (NCI-H660) prostate cancer cells after treatment with vehicle or estrogenic compounds were assessed by viability assays and quantitative polymerase chain reaction, respectively. All statistical tests were two-sided. Results: We identified an 87-gene expression signature that distinguishes TMPRSS2-ERG fusion prostate cancer as a discrete molecular entity (area under the curve = 0.80, 95% confidence interval [CI] = 0.792 to 0.81, P <. 001). Computational analysis suggested that this fusion signature was associated with estrogen receptor (ER) signaling. Viability of NCI-H660 cells decreased after treatment with estrogen (viability normalized to day 0, estrogen vs vehicle at day 8, mean = 2.04 vs 3.40, difference = 1.36, 95% CI = 1.12 to 1.62) or ERβ agonist (ERβ agonist vs vehicle at day 8, mean = 1.86 vs 3.40, difference = 1.54, 95% CI = 1.39 to 1.69) but increased after ERα agonist treatment (ERα agonist vs vehicle at day 8, mean = 4.36 vs 3.40, difference = 0.96, 95% CI = 0.68 to 1.23). Similarly, expression of TMPRSS2-ERG decreased after ERβ agonist treatment (fold change over internal control, ERβ agonist vs vehicle at 24 hours, NCI-H660, mean = 0.57- vs 1.0-fold, difference = 0.43-fold, 95% CI = 0.29- to 0.57-fold) and increased after ERα agonist treatment (ERα agonist vs vehicle at 24 hours, mean = 5.63- vs 1.0-fold, difference = 4.63-fold, 95% CI = 4.34- to 4.92-fold). Conclusions: TMPRSS2-ERG fusion prostate cancer is a distinct molecular subclass. TMPRSS2-ERG expression is regulated by a novel ER-dependent mechanism. © The Author 2008. Published by Oxford University Press.

1 - 11 of 11
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf