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  • Holm, Johanna, et al. (författare)
  • Associations of breast cancer risk prediction tools with tumor characteristics and metastasis
  • 2016
  • Ingår i: Journal of Clinical Oncology. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0732-183X. ; 34:3, s. 251-U109
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The association between established risk factors for breast cancer and subtypes or prognosis of the disease is not well known. We analyzed whether the Tyrer-Cuzick–predicted 10-year breast cancer risk score (TCRS), mammographic density (MD), and a 77-single nucleotide polymorphism polygenic risk score (PRS) were associated with breast cancer tumor prognosticators and risk of distant metastasis. Patients and Methods: We used a case-only design in a population-based cohort of 5,500 Swedish patients with breast cancer. Logistic and multinomial logistic regression of outcomes, estrogen receptor (ER) status, lymph node involvement, tumor size, and grade was performed with TCRS, PRS, and percent MD as exposures. Cox proportional hazard models were used to estimate hazard ratios (HRs) of distant metastasis. Results: Women at high risk for breast cancer based on PRS and/or TCRS were significantly more likely to be diagnosed with favorable prognosticators, such as ER-positive and low-grade tumors. In contrast, PRS weighted on ER-negative disease was associated with ER-negative tumors. When stratifying by age, the associations of TCRS with favorable prognosticators were restricted to women younger than age 50. Women scoring high in both TCRS and PRS had a lower risk of distant metastasis (HR, 0.69; 95% CI, 0.49 to 0.98). MD was not associated with any of the examined prognosticators. Conclusion: Women at high risk for breast cancer based on genetic and lifestyle factors were significantly more likely to be diagnosed with breast cancers with a favorable prognosis. Better knowledge of subtype- specific risk factors could be vital for the success of prevention programs aimed at lowering mortality.
  • Holm, Johanna, et al. (författare)
  • Risk factors and tumor characteristics of interval cancers by mammographic density
  • 2015
  • Ingår i: Journal of Clinical Oncology. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0732-183X. ; 33:9, s. 1030-
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To compare tumor characteristics and risk factors of interval breast cancers and screen-detected breast cancers, taking mammographic density into account. Patients and Methods: Women diagnosed with invasive breast cancer from 2001 to 2008 in Stockholm, Sweden, with data on tumor characteristics (n ? 4,091), risk factors, and mammographic density (n ? 1,957) were included. Logistic regression was used to compare interval breast cancers with screen- detected breast cancers, overall and by highest and lowest quartiles of percent mammo- graphic density. Results: Compared with screen-detected breast cancers, interval breast cancers in nondense breasts (? 20% mammographic density) were significantly more likely to exhibit lymph node involvement (odds ratio [OR], 3.55; 95% CI, 1.74 to 7.13) and to be estrogen receptor negative (OR, 4.05; 95% CI, 2.24 to 7.25), human epidermal growth factor receptor 2 positive (OR, 5.17; 95% CI, 1.64 to 17.01), progesterone receptor negative (OR, 2.63; 95% CI, 1.58 to 4.38), and triple negative (OR, 5.33; 95% CI, 1.21 to 22.46). In contrast, interval breast cancers in dense breasts (? 40.9% mammographic density) were less aggressive than interval breast cancers in nondense breasts (overall difference, P ? .008) and were phenotypically more similar to screen-detected breast cancers. Risk factors differentially associated with interval breast cancer relative to screen- detected breast cancer after adjusting for age and mammographic density were family history of breast cancer (OR, 1.32; 95% CI, 1.02 to 1.70), current use of hormone replacement therapy (HRT; OR, 1.84; 95% CI, 1.38 to 2.44), and body mass index more than 25 kg/m2 (OR, 0.49; 95% CI, 0.29 to 0.82). Conclusion: Interval breast cancers in women with low mammographic density have the most aggressive phenotype. The effect of HRT on interval breast cancer risk is not fully explained by mammographic density. Family history is associated with interval breast cancers, possibly indicating disparate genetic background of screen-detected breast cancers and interval breast cancers.
  • Abrahamsson, Jonas, 1954, et al. (författare)
  • Response-guided induction therapy in pediatric acute myeloid leukemia with excellent remission rate.
  • 2011
  • Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - : American Society of Clinical Oncology. - 1527-7755 .- 0732-183X. ; 29:3, s. 310-5
  • Tidskriftsartikel (refereegranskat)abstract
    • To evaluate the early treatment response in children with acute myeloid leukemia (AML) using a response-guided induction strategy that includes idarubicin in the first course.
  • Agudo, Antonio, et al. (författare)
  • Impact of Cigarette Smoking on Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Study.
  • 2012
  • Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 1527-7755 .- 0732-183X.
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSEOur aim was to assess the impact of cigarette smoking on the risk of the tumors classified by the International Agency for Research on Cancer as causally associated with smoking, referred to as tobacco-related cancers (TRC). METHODSThe study population included 441,211 participants (133,018 men and 308,193 women) from the European Prospective Investigation Into Cancer and Nutrition. We investigated 14,563 participants who developed a TRC during an average follow-up of 11 years. The impact of smoking cigarettes on cancer risk was assessed by the population attributable fraction (AF(p)), calculated using the adjusted hazard ratios and 95% CI for current and former smokers, plus either the prevalence of smoking among cancer cases or estimates from surveys in representative samples of the population in each country.ResultsThe proportion of all TRC attributable to cigarette smoking was 34.9% (95% CI, 32.5 to 37.4) using the smoking prevalence among cases and 36.2% (95% CI, 33.7 to 38.6) using the smoking prevalence from the population. The AF(p) were above 80% for cancers of the lung and larynx, between 20% and 50% for most respiratory and digestive cancers and tumors from the lower urinary tract, and below 20% for the remaining TRC. CONCLUSIONUsing data on cancer incidence for 2008 and our AF(p) estimates, about 270,000 new cancer diagnoses per year can be considered attributable to cigarette smoking in the eight European countries with available data for both men and women (Italy, Spain, United Kingdom, the Netherlands, Greece, Germany, Sweden, Denmark).
  • Albertsen, B. K., et al. (författare)
  • Intermittent Versus Continuous PEG-Asparaginase to Reduce Asparaginase-Associated Toxicities: A NOPHO ALL2008 Randomized Study
  • 2019
  • Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 37:19, s. 1638-1646
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE Asparaginase is an essential drug in childhood acute lymphoblastic leukemia (ALL) therapy and is frequently given for months to obtain continuous asparagine depletion. We randomly assigned patients to continuous versus intermittent pegylated-asparaginase (PEG-asp) treatment, hypothesizing there would be decreased toxicity with unchanged efficacy. METHODS Children (median age, 4.2 years) treated for non-high-risk ALL according to the Nordic Society for Pediatric Hematology and Oncology ALL2008 protocol received five intramuscular PEG-asp injections (1,000 IU/m(2)) every two weeks and were then randomly assigned to additional three doses (6-week intervals [experimental arm], n = 309) versus 10 doses (2-week intervals [standard arm], n = 316). The primary end point was noninferior (6% margin) disease-free survival. Toxicity reduction was a secondary end point. Occurrence of asparaginase-associated hypersensitivity, pancreatitis, osteonecrosis, and thromboembolism were prospectively registered. RESULTS After a median follow-up of 4.1 years, the 5-year disease-free survival was 92.2% (95% CI, 88.6 to 95.8) and 90.8% (95% CI, 87.0 to 94.6) in the experimental and standard arms, respectively. The 3-year cumulative incidence of any first asparaginase-associated toxicity (hypersensitivity [n = 13]; osteonecrosis [n = 29]; pancreatitis [n = 24]; thromboembolism [n = 17]) was 9.3% in the experimental arm and 18.1% in the standard arm (P = .001). Asparaginase-associated toxicity reduction was confirmed in sex- and risk-group-adjusted Cox regression analysis stratified by age (>= 10 and < 10 years; hazard ratio, 0.48; P = .001). The experimental arm had the lowest incidences of all four toxicities, reaching significance for pancreatitis (6-month risk, 5.8% v 1.3%; P = .002). CONCLUSION The excellent cure rates and reduced toxicity risk support the use of intermittent PEG-asp therapy after the first 10 weeks in future childhood ALL trials that apply prolonged PEG-asp therapy.
  • Ambros, I. M., et al. (författare)
  • Age Dependency of the Prognostic Impact of Tumor Genomics in Localized Resectable MYCN-Nonamplified Neuroblastomas. Report From the SIOPEN Biology Group on the LNESG Trials and a COG Validation Group
  • 2020
  • Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 38:31, s. 3685-
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSEFor localized, resectable neuroblastoma without MYCN amplification, surgery only is recommended even if incomplete. However, it is not known whether the genomic background of these tumors may influence outcome.PATIENTS AND METHODSDiagnostic samples were obtained from 317 tumors, International Neuroblastoma Staging System stages 1/2A/2B, from 3 cohorts: Localized Neuroblastoma European Study Group I/II and Children's Oncology Group. Genomic data were analyzed using multi- and pangenomic techniques and fluorescence in-situ hybridization in 2 age groups (cutoff age, 18 months) and were quality controlled by the International Society of Pediatric Oncology European Neuroblastoma (SIOPEN) Biology Group.RESULTSPatients with stage 1 tumors had an excellent outcome (5-year event-free survival [EFS] standard deviation [SD], 95% +/- 2%; 5-year overall survival [OS], 99% +/- 1%). In contrast, patients with stage 2 tumors had a reduced EFS in both age groups (5-year EFS +/- SD, 84% +/- 3% in patients < 18 months of age and 75% 7% in patients >= 18 months of age). However, OS was significantly decreased only in the latter group (5-year OS +/- SD in < 18months and 18months, 96% +/- 2% and 81% +/- 7%, respectively; P = .001). In < 18months, relapses occurred independent of segmental chromosome aberrations (SCAs); only 1p loss decreased EFS (5-year EFS SD in patients 1p loss and no 1p loss, 62% +/- 13% and 87% +/- 3%, respectively; P = .019) but not OS (5-year OS +/- SD, 92% +/- 8% and 97% +/- 2%, respectively). In patients >= 18 months, only SCAs led to relapse and death, with 11q loss as the strongest marker (11q loss and no 11q loss: 5-year EFS +/- SD, 48% +/- 16% and 85% +/- 7%, P = .033; 5-year OS +/- SD, 46% +/- 22% and 92% +/- 6%, P = .038).CONCLUSIONGenomic aberrations of resectable non-MYCN-amplified stage 2 neuroblastomas have a distinct age-dependent prognostic impact. Chromosome 1p loss is a risk factor for relapse but not for diminished OS in patients < 18 months, SCAs (especially 11q loss) are risk factors for reduced EFS and OS in those > 18months. In older patients with SCA, a randomized trial of postoperative chemotherapy compared with observation alone may be indicated.
  • Anand, Aseem, et al. (författare)
  • Quantitative imaging by automated bone scan index (BSI) as a response biomarker in standard clinical care of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide
  • 2015
  • Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 33:7 Suppl, s. 288-288
  • Konferensbidrag (refereegranskat)abstract
    • Background: Enzalutamide (ENZ), an androgen receptor antagonist therapy, was approved for patients (pts) with mCRPC. However, in standard of care for mCRPC pts, change in prostate specific antigen (PSA) is not accepted as an efficacy response measurement and the radiological change is inadequately measured in an interpreter-dependent subjective analysis of bone scan. Therefore, an objective efficacy response biomarker is warranted. In this registry study, we evaluated BSI as a quantitative analysis of bone scintigraphy, to access response in mCRPC pts being treated with ENZ.Methods: Pts with mCRPC, at Skåne University Hospital (SUH), Sweden, who initiated treatment with ENZ after failing chemotherapy were eligible for the study. Primary objective was to associate the change in BSI and PSA, after 12 weeks (wks) of treatment with EZN, with overall survival (OS). Automated BSI generated by EXINI boneBSI platform is quantitative representation of tumor burden as a percent of total skeletal mass. Bivariate cox regression analysis was used to evaluate the association of BSI and PSA with OS.Results: Thirty-five pts, who initiated ENZ treatment at (SUH), were eligible for the BSI analysis. Follow-up scans for the BSI analysis were available from 24 pts. Median baseline BSI value was 2.92 (range: 0.0-11.72) and at follow-up the median BSI value was 2.83 (range: 0.0-12.65). OS was associated with BSI at both baseline and at follow-up as opposed to that of PSA (table 1). The change in BSI between baseline and follow-up was also significantly associated with OS, whereas the change in PSA was not.Conclusions: Automated BSI and its relative change were observed to be associated with OS in mCRPC pts receiving ENZ as standard of care treatment. The result deserves further validation, in controlled investigational studies, of BSI as a quantitative imaging biomarker indicative of efficacy response to second-line treatment in mCRPC pts.
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