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1.
  • Glimelius, Bengt, et al. (författare)
  • U-CAN : a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
  • 2018
  • Ingår i: ; 57:2, s. 187-194
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.
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2.
  • Lindman, H., et al. (författare)
  • A randomised study of tailored toxicity-based dosage of fluorouracil-epirubicin-cyclophosphamide chemotherapy for early breast cancer (SBG 2000-1)
  • Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 94, s. 79-86
  • Tidskriftsartikel (refereegranskat)abstract
    • Study aim: Retrospective studies have demonstrated a worse outcome in breast cancer patients not developing leukopenia during adjuvant chemotherapy. The SBG 2000-1 is the first randomised trial designed to compare individually dosed chemotherapy without G-CSF support based on grade of toxicity to standard-dosed chemotherapy based on body surface area (BSA). Methods: Patients with early breast cancer were included and received the first cycle of standard FEC (fluorouracil 600 mg/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2). Patients with nadir leukopenia grade 0–2 after first cycle were randomised between either 6 additional courses of tailored FEC with increased doses (E 75–90 mg/m2, C 900–1200 mg/m2) or fixed treatment with 6 standard FEC. Patients with grade 3–4 leukopenia were registered and treated with 6 standard FEC. Primary end-point was distant disease-free survival (DDFS). Results: The study enrolled 1535 patients, of which 1052 patients were randomised to tailored FEC (N = 524) or standard FEC (N = 528), whereas 401 patients with leukopenia grade 3–4 continued standard FEC and formed the registered cohort. Dose escalation did not statistically significantly improve 10-year DDFS (79% and 77%, HR 0.87, CI 0.67–1.14, P = 0.32) or OS (82% and 78%, respectively, HR 0.89, CI 0.57–1.16, P = 0.38). Corresponding estimates for the registered group of patients were DDFS 79% and OS 82%, respectively. Conclusions: The SBG 2000-1 study failed to show a statistically significant improvement of escalated and tailored-dosed chemotherapy compared with standard BSA-based chemotherapy in patients with low haematological toxicity, although all efficacy parameters showed a numerical advantage for tailored treatment.
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3.
  • Rosell, J., et al. (författare)
  • Time dependent effects of adjuvant tamoxifen therapy on cerebrovascular disease: results from a randomised trial
  • 2011
  • Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 1532-1827 .- 0007-0920. ; 104:6, s. 899-902
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Tamoxifen has been associated with an increased risk of stroke. There is, however, little information on the effect in the post-treatment period. Using data from the Swedish Breast Cancer Group adjuvant trial of 5 vs 2 years of tamoxifen treatment, we now report both short-term and long-term effects on morbidity as well as mortality because of cerebrovascular disease. METHODS: Data from the Swedish National Hospital Discharge Registry combined with information from the Swedish Cause of Death Registry was used to define events of disease. Hazard ratios (HRs) were estimated using Cox regression. RESULTS: Comparing patients randomised to 5 years of tamoxifen with patients randomised to 2 years of tamoxifen, the incidence of cerebrovascular diseases was increased (HR 1.70, 95% CI 1.05-2.75) during the active treatment phase and reduced after the active treatment period (HR 0.78, 95% CI 0.63-0.96), and the difference in HR between the two time-periods was significant (P 0.0033). The mortality from cerebrovascular diseases was increased during the treatment period (HR 3.18, 95% CI 1.03-9.87) and decreased during the post-treatment period (HR 0.60, 95% CI 0.40-0.90) with a significant difference in HR between the two periods of follow-up (P=0.0066). Similar results were seen for subgroups of cerebrovascular diseases, such as stroke and ischaemic stroke. CONCLUSION: In an adjuvant setting, tamoxifen was associated with an increased risk of cerebrovascular disease during treatment, but a decreased risk in the post-treatment period. British Journal of Cancer (2011) 104, 899-902. doi: 10.1038/bjc. 2011.45 www. bjcancer. com
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4.
  • Wilking, N., et al. (författare)
  • Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
  • 2007
  • Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 18:4, s. 694-700
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below theage of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. © 2007 Oxford University Press.
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5.
  • Ciray, Ipek, et al. (författare)
  • Early response of breast cancer bone metastases to chemotherapy evaluated with MR imaging
  • 2001
  • Ingår i: Acta Radiologica. - 0284-1851 .- 1600-0455. ; 42:2, s. 198-206
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • PURPOSE: To compare T1-weighted spin-echo and fat-suppressed long echo time inversion recovery turbo spin-echo (long TE IR-TSE) MR images in the evaluation of early response of breast cancer bone metastases to chemotherapy. MATERIAL AND METHODS: Eighteen breast cancer patients with known bone metastases were investigated prospectively by MR, using T1-weighted and long TE IR-TSE sequences on the sternum, spine, pelvis and proximal femora, before and after a median of 6 courses of chemotherapy. Therapeutic response evaluation with MR was based on change in tumor size assessed quantitatively by measuring all focal metastases, and change in pattern and signal intensity (SI) of the metastases, assessed visually. Combined response evaluation based on clinical findings, conventional radiography, and scintigraphy was used as reference. RESULTS: Progressive disease (2 patients) and no change (4 patients) were assessed equally well on both MR sequences. Long TE IR-TSE demonstrated partial response with higher accuracy than T1-weighted images, 58% (7/12 patients) vs. 17% (2/12 patients). In patients without progression there was an SI increase in or around the metastases in 6 patients on T1-weighted images and in 7 patients on long TE IR-TSE images. CONCLUSION: The long TE IR-TSE sequence demonstrated early partial response of breast cancer bone metastases to chemotherapy more accurately than the T1-weighted sequence.
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6.
  • Dahlberg, L., et al. (författare)
  • Health care costs for treatment of disseminated breast cancer
  • 2009
  • Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 45:11, s. 1987-1991
  • Tidskriftsartikel (refereegranskat)abstract
    • The rapid development of the care makes it important to have relevant cost information for cost-effectiveness assessments. The aim of this study is to estimate the health care cost of a disseminated breast cancer relapse in Sweden. A retrospective cohort study of women with disseminated breast cancer in Sweden was done. The individual case records were reviewed and all data concerning treatments, hospitalisation, examinations and palliative care were collected. The study included 53 patients with a total mean cost of euro93,700 (95% Confidence Interval (CI): euro78,500-euro109,600). Drugs and hospitalisations were the largest single cost sources. HER2-positive patients had slightly higher mean costs (euro123,300), while triple negative patients had slightly lower mean costs (euro70,600). The current costs for patients with disseminated breast cancer are considerably higher than those previously shown, which may have important consequences for economic evaluations of interventions aimed at reducing the risk of disseminated breast cancer.
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7.
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8.
  • Fredholm, Hanna, et al. (författare)
  • Breast cancer in young women : poor survival despite intensive treatment
  • 2009
  • Ingår i: PLoS one. - 1932-6203. ; 4:11, s. e7695-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Breast cancer is uncommon in young women and correlates with a less favourable prognosis; still it is the most frequent cancer in women under 40, accounting for 30-40% of all incident female cancer. The aim of this study was to study prognosis in young women, quantifying how much stage at diagnosis and management on the one hand, and tumour biology on the other; each contribute to the worse prognosis seen in this age group. METHODOLOGY/PRINCIPAL FINDINGS: In a registry based cohort of women aged 20-69 (n = 22 017) with a primary diagnosis of invasive breast cancer (1992-2005), women aged 20-34 (n = 471), 35-39 (n = 858) and 40-49 (n = 4789) were compared with women aged 50-69 years (n = 15 899). The cumulative 5-year relative survival ratio and the relative excess mortality (RER) were calculated. The cumulative 5-year relative survival ratio was lowest in women aged 20-34. The RER was 2.84 for women aged 20-34 and decreased with increasing age (RER 1.76 and 1.17 for women aged 35-39 and 40-49, respectively). The excess risk was, however, present only in disease stages I and II. For women aged 20-34 with stage I disease RER was 4.63, and 6.70 in the subgroup with tumour size 1-10 mm. The absolute difference in stage I between the youngest and the reference groups amounted to nearly 8%, with a 90% 5-year survival in women aged 20-34. In stages IIa and IIb, the relative excess risk was not as dramatic, but the absolute differences approached 15%. The youngest women with small tumours generally received more aggressive treatment than women in older age groups. CONCLUSIONS: After correction for stage, tumour characteristics and treatment, age remained an independent risk factor for breast cancer death in women <35 years of age. The excess risk for young women was only seen in early stages of disease and was most pronounced in women with small tumours. Young women affected by breast cancer have a high risk of dying compared to their middle-aged counterparts even if diagnosed early and receiving an intense treatment.
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9.
  • Fredholm, Hanna, et al. (författare)
  • Breast cancer in young women and prognosis : How important are proliferation markers?
  • 2017
  • Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 84, s. 278-289
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim:Compared to middle-aged women, young women with breast cancer have a higher risk of systemic disease. We studied expression of proliferation markers in relation to age and subtype and their association with long-term prognosis.Methods:Distant disease-free survival (DDFS) was studied in 504 women aged <40 years and 383 women aged >= 40 years from a population-based cohort. Information on patient characteristics, treatment and follow-up was collected from medical records. Tissue microarrays were produced for analysis of oestrogen receptor, progesterone receptor (PR), Her2, Ki-67 and cyclins.Results: Young women with luminal tumours had significantly higher expression of Ki-67 and cyclins. Proliferation markers were prognostic only within this subtype. Ki-67 was a prognostic indicator only in young women with luminal PR+ tumours. The optimal cut-off for Ki-67 varied by age. High expression of cyclin E1 conferred a better DDFS in women aged <40 years with luminal PR- tumours (hazard ratio [HR] 0.47 [0.24-0.92]). Age < 40 years was an independent risk factor of DDFS exclusively in women with luminal B PR+ tumours (HR 2.35 [1.22-4.50]). Young women with luminal B PR- tumours expressing low cyclin E1 had a six-fold risk of distant disease compared with luminal A ( HR 6.21 [2.17-17.6]).Conclusions:The higher expression of proliferation markers in young women does not have a strong impact on prognosis. Ki-67 is only prognostic in the subgroup of young women with luminal PR tumours. The only cyclin adding prognostic value beyond subtype is cyclin E1. Age is an independent prognostic factor only in women with luminal B PR+ tumours.
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10.
  • Fredholm, Hanna, et al. (författare)
  • Long-term outcome in young women with breast cancer : a population-based study
  • 2016
  • Ingår i: ; 160:1, s. 131-143
  • Tidskriftsartikel (refereegranskat)abstract
    • Whether young age at diagnosis of breast cancer is an independent risk factor for death remains controversial, and the question whether young age should be considered in treatment decisions is still to be answered. From a population-based cohort of 22,017 women with breast cancer, all women < 35 years (n = 471) were compared to a random sample of 700 women aged 35-69 years from the same cohort. Information on patient and tumor characteristics, treatment, and follow-up was collected from the medical records. Tissue microarrays were produced for analysis of classical biomarkers. Breast cancer-specific survival (BCSS), distant disease-free survival (DDFS), and locoregional recurrence-free survival (LRFS) by age were compared using women 50-69 years as reference. At 10 years follow-up, women < 35 years and 35-39 years had a worse BCSS [age < 35 years 69 % (HR 2.75, 95 % CI 1.93-3.94), age 35-39 years 76 % (HR 2.33, 95 % CI 1.54-3.52), age 40-49 years 84 % (HR 1.53, 95 % CI 0.97-2.39), and age 50-69 years 89 % (reference)]. The worse BCSS was statistically significant in stages I-IIa and Luminal B tumors. At multivariate analysis age < 35 years and 35-39 years confined a risk in LRFS (HR 2.13, 95 % CI 1.21-3.76 and HR 1.97, 95 % CI 1.06-3.68) but not in DDFS and BCSS. In the subgroup of women < 40 years with luminal tumors stage I-IIa, low age remained an independent risk factor also in DDFS (HR 1.87, 95 % CI 1.03-3.44). Young women have a high risk of systemic disease even when diagnosed in an early stage. The excess risk of relapse is most pronounced in Luminal B tumors, where low age is an independent prognostic factor of DDFS and LRFS.
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