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  • 51.
    Velikyan, Irina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Wennborg, Anders
    Affibody AB, Solna, Sweden..
    Feldwisch, Joachim
    Affibody AB, Solna, Sweden..
    Orlova, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Lindman, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Carlsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Good manufacturing practice compliant production of a Ga-68-labelled Affibody agent for breast cancer imaging: first-in-human2015In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 58, p. S358-S358Article in journal (Other academic)
  • 52.
    Wickberg, Asa
    et al.
    Fac Med & Hlth, Dept Surg, SE-70182 Orebro, Sweden.
    Liljegren, Goran
    Fac Med & Hlth, Dept Surg, SE-70182 Orebro, Sweden.
    Killander, Fredrika
    Skane Univ Hosp, Lund, Sweden;Lund Univ, Lund, Sweden.
    Lindman, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Bjohle, Judith
    Univ Hosp, Stockholm, Sweden;Karolinska Inst, Stockholm, Sweden.
    Carlberg, Michael
    Fac Med & Hlth, Dept Oncol, SE-70182 Orebro, Sweden.
    Blomqvist, Carl
    Univ Helsinki, Dept Oncol, Helsinki, Finland.
    Ahlgren, Johan
    Fac Med & Hlth, Dept Oncol, SE-70182 Orebro, Sweden.
    Villman, Kenneth
    Fac Med & Hlth, Dept Oncol, SE-70182 Orebro, Sweden.
    Omitting radiotherapy in women >= 65 years with low-risk early breast cancer after breast-conserving surgery and adjuvant endocrine therapy is safe2018In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 44, no 7, p. 951-956Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of this study was to verify if radiotherapy (RT) safely can be omitted in older women treated for estrogen-receptor positive early breast cancer with breast-conserving surgery (BCS) and endocrine therapy (ET). Patients and Methods: Eligibility criteria were: consecutive patients with age >= 65 years, BCS + sentinel node biopsy, clear margins, unifocal T1N0M0 breast cancer tumor, Elston-Ellis histological grade 1 or 2 and estrogen receptor-positive tumor. After informed consent, adjuvant ET for 5 years was prescribed. Primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were contralateral breast cancer and overall survival. Results: Between 2006 and 2012, 603 women were included from 14 Swedish centers. Median age was 71.1 years (range 65-90). After a median follow-up of 68 months 16 IBTR (cumulative incidence at five-year follow-up; 1.2%, 95% CI, 0.6% to 2.5%), 6 regional recurrences (one combined with IBTR), 2 distant recurrences (both without IBTR or regional recurrence) and 13 contralateral breast cancers were observed. There were 48 deaths. One death (2.1%) was due to breast cancer and 13 (27.1%) were due to other cancers (2 endometrial cancers). Five-year overall survival was 93.0% (95% CI, 90.5% to 94.9%). Conclusion: BCS and ET without RT seem to be a safe treatment option in women >= 65 years with early breast cancer and favorable histopathology. The risk of IBTR is comparable to the risk of contralateral breast cancer. Moreover, concurrent morbidity dominates over breast cancer as leading cause of death in this cohort with low-risk breast tumors.

  • 53.
    Wickström, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Haglund, Caroline
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindman, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gullbo, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The novel alkylating prodrug J1: diagnosis directed activity profile ex vivo and combination analyses in vitro2008In: Investigational new drugs, ISSN 0167-6997, E-ISSN 1573-0646, Vol. 26, no 3, p. 195-204Article in journal (Refereed)
    Abstract [en]

    Objective: The dipeptide J1 acts as a prodrug of melphalan with a significant increased potency in vitro resulting from activation by cellular aminopeptidases. The current study was performed to evaluate the ex vivo profile of J1 using 176 primary tumor cell cultures from patients. In addition, the activity of J1 in combination with eight standard drugs, representing different mechanistic classes, was studied in nine different human tumor cell lines of different histopathological origin. Methods: Ex vivo evaluation of tumor type selectivity, was performed using the established fluorometric microculture cytotoxicity assay (FMCA). Combinations between J1 and eight standard chemotherapeutic drugs were analyzed using the median-effect method. Results: The prodrug J1 expressed approximately 50- to 100-fold higher potency but similar activity profile as that of its metabolite, melphalan. The difference was greater in some diagnoses (e.g. breast cancer, NHL and AML), and exceptionally high in some breast cancer samples with aggressive phenotypes. Combination analysis of J1 and standard chemotherapeutics yielded several potentially additive and synergistic interactions, most striking for etoposide with significant synergism in all studied cell lines. Conclusions: In conclusion, the ex vivo profile suggests that further evaluation of J1 as the alkylating agent in for example aggressive breast cancer might be of particular interest, preferentially in combination with DNA-topoisomerase II inhibitors like etoposide.

  • 54. Wigertz, Annette
    et al.
    Ahlgren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg.
    Holmqvist, Marit
    Fornander, Tommy
    Adolfsson, Jan
    Lindman, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Lambe, Mats
    Adherence and discontinuation of adjuvant hormonal therapy in breast cancer patients: a population-based study2012In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 133, no 1, p. 367-373Article in journal (Refereed)
    Abstract [en]

    Adherence to long-term pharmacological treatment for chronic conditions is often less than optimal. Till date, a limited number of population-based studies have assessed adherence to adjuvant hormonal therapy in breast cancer, a therapy with proven benefits in terms of reductions of recurrence and mortality. We aimed to examine rates of adherence and early discontinuation in Sweden where prescribed medications are subsidized for all residents and made available at reduced out-of-pocket costs. Individual-level data were obtained from Regional Clinical Quality Breast Cancer Registers, the Swedish Prescribed Drug Register, and several other population-based registers. Multivariate logistic regression was used to analyze factors associated with adherence to prescribed medication for a period of 3 years. Between January 1 and December 31, 2005, 1,741 patients in central Sweden were identified with estrogen receptor positive breast cancer, and at least one prescription dispensation of either tamoxifen or an aromatase inhibitor. Of these women, 1,193 (69%) were fully adherent to therapy for 3 years (medication possession ratio of 80% or higher and a maximum of 180 days between refills). During the 3-year follow-up, 215 women (12%) had prematurely discontinued therapy. Adherence was positively associated with younger age, large tumor size, being married, and being born in the Nordic countries, while no clear association was observed with education or income. During the 3 years of follow-up, 31% of women were non-adherent to therapy. Further efforts must be undertaken to promote adherence over the entire recommended treatment period.

  • 55.
    Zhou, Wenjing
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Jirström, Karin
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sollie, Thomas
    Lindman, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sørlie, Therese
    Blomqvist, Carl
    Wärnberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Molecular subtypes in ductal carcinoma in situ of the breast and their relation to prognosis: a population-based cohort study2013In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, p. 512-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Different molecular subtypes of breast cancer have been identified based on gene expression profiling. Treatment suggestions based on an approximation of these subtypes by immunohistochemical criteria have been published by the St Gallen international expert consensus panel. Ductal carcinoma in situ (DCIS) can be classified into the same molecular subtypes. Our aim was to study the relation between these newly defined subtypes and prognosis in DCIS.

    METHODS: TMA including 458 women from a population-based cohort with DCIS diagnosed 1986-2004 was used. Stainings for ER, PR, HER2 and Ki67 were used to classify the surrogate molecular subtypes according to the St Gallen criteria from 2011. The associations with prognosis were examined using Kaplan-Meier analyses and Cox proportional hazards regression models.

    RESULTS: Surrogate molecular subtyping could be done in 381 cases. Mean follow up was 164 months. Of the classified DCIS 186 were Luminal A (48.8%), 33 Luminal B/HER2- (8.7%), 74 Luminal B/HER2+ (17.4%), 61 HER2+/ER- (16.0%) and 27 Triple Negative (7.1%). One hundred and two women had a local recurrence of which 58 were invasive. Twenty-two women had generalised disease, 8 without a prior local recurrence. We could not find a prognostic significance of the molecular subtypes other than a higher risk of developing breast cancer after more than 10 years of follow-up among women with a Triple Negative DCIS (OR 3.2; 95% CI 1.1-9.8).

    CONCLUSIONS: The results from this large population-based cohort, with long-term follow up failed to demonstrate a prognostic value for the surrogate molecular subtyping of DCIS using the St Gallen criteria up to ten years after diagnosis. More than ten years after diagnosis Triple Negative DCIS had an elevated risk of recurrence.

12 51 - 55 of 55
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