| 1. |
- Bergh, Jonas, et al.
(författare)
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Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer : A randomised trial
- 2000
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 356:9239, s. 1384-1391
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chemotherapy drug distribution varies greatly among individual patients. Therefore, we developed an individualised fluorouracil, epirubicin, cyclophosphamide (FEC) regimen to improve outcomes in patients with high-risk early breast cancer. We then did a randomised trial to compare this individually tailored FEC regimen with conventional adjuvant chemotherapy followed by consolidation with high-dose chemotherapy with stem-cell support. Methods: 525 women younger than 60 years of age with high-risk primary breast cancer were randomised after surgery to receive nine cycles of tailored FEC to haematological equitoxicity with granulocyte colony-stimulating factor (G-CSF) support (n=251), or three cycles of FEC at standard doses followed by high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTCb), and peripheral-blood stem-cell or bone-marrow support (n=274). Both groups received locoregional radiation therapy and tamoxifen for 5 years. The primary outcome measure was relapse-free survival, and analysis was by intention to treat. Findings: At a median follow-up of 34.3 months, there were 81 breast-cancer relapses in the tailored FEC group versus 113 in the CTCb group (double triangular method p=0.04). 60 deaths occurred in the tailored FEC group and 82 in the CTCb group (log-rank p=0.12). Patients in the CTCb group experienced more grade 3 or 4 acute toxicity compared with the tailored FEC group (p<0.0001). Two treatment-related deaths (0.7%) occurred in the CTCb group. Six patients in the tailored FEC group developed acute myeloid leukaemia and three developed myelodysplastic syndrome. Interpretation: Tailored FEC with G-CSF support resulted in a significantly improved relapse-free survival and fewer grade 3 and 4 toxicities compared with marrow-supported high-dose chemotherapy with CTCb as adjuvant therapy of women with high-risk primary breast cancer.
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| 2. |
- Wilking, Nils, et al.
(författare)
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Drug utilization research in the area of cancer drugs
- 2016
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Ingår i: Drug Utilization Research: Methods and Applications. - 9781118949788 ; , s. 315-327
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Bokkapitel (refereegranskat)abstract
- Increased biological understanding of cancer diseases has resulted in a paradigm shift in the medical treatment of cancer. Despite encouraging advances, most cancer types are still incurable and cancer is the second most common cause of death in developed countries.The high price of cancer drugs is a major challenge to equal access and puts heavy strains on public health care payers. After sharp increases in the 2000s, total expenditures on cancer drugs have levelled off due to patent expiration of many expensive and widely used drugs.Cancer drug utilization studies cover a great variety of topics. Four main research areas are patient adherence, physician adherence to guidelines, effectiveness and safety (outcomes research) and access (market uptake).Most cancer drugs are classified under Anatomical Therapeutic Chemical (ATC) group L. The use of defined daily dose (DDD) as a measurement unit is feasible for oral cancer drugs. As most cancer drugs are administered as infusions or injections at hospitals, usage is commonly measured in milligrams.Drug utilization research in the area of cancer is faced with a lack of data. Comparisons are challenging, as prices and population bases vary across regions. The linkage of registries and health care databases that include cancer drug usage will create improved opportunities in the future.
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| 3. |
- Bergenmar, Mia, et al.
(författare)
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Audio-recorded information to patients considering participation in cancer clinical trials - a randomized study
- 2014
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Ingår i: Acta Oncologica. - 1651-226X. ; 53:9, s. 1197-1204
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Tidskriftsartikel (refereegranskat)abstract
- Background. Patient information in cancer clinical trial is challenging. The value of audio-recording interventions for patients considering participating in clinical trials is unclear. The primary aim of this randomized study was to investigate effects of audio-recorded information on knowledge and understanding in patients considering participation in a clinical trial. Material and methods. Patients scheduled for information about a phases 2 or 3 trial by one of the 13 participating oncologists at the Department of Oncology during the study period (2008-2013) were eligible. The intervention consisted of an audio-recording on compact disc (CD) of the information at the medical consultation in which the patients were informed about a trial. Knowledge and understanding was measured by the questionnaire, Quality of Informed Consent. Results. A total of 130 patients were randomized, 70% of the calculated sample size (n = 186). Sixty-seven patients were randomized to the intervention. In total, 101 patients (78%) completed questionnaires. No statistical significant differences were found between the groups with respect to knowledge and understanding. The level of knowledge was relatively high, with the exceptions of the risks associated with, and the unproven nature of, the trial. Overall, patients who declined participation scored statistically significant lower on knowledge. Conclusion. The present study was underpowered and the results should therefore be interpreted with caution. Still, 130 patients were included with a response rate of 78%. A CD including the oral information about a clinical trial did not show any effects on knowledge or understanding. However, the levels of knowledge were high, possible due to the high levels of education in the study group. Information on risks associated with the trial is still an area for improvement.
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| 4. |
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| 5. |
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| 6. |
- Jönsson, Bengt, et al.
(författare)
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Comparator report on patient access to cancer medicines in Europe revisited
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In a new report, the Swedish Institute for Health Economics (IHE) compares the cancer situation in EU28 plus Norway and Switzerland. The report builds on a previous comparative study conducted in 2005 and provides a comprehensive view of the development of cancer in Europe over the past two decades. The report shows that the number of people diagnosed with cancer continue to increase in Europe, up by 30 percent between 1995 and 2012 due to a growing and aging population. Despite this growth and an increased spending on cancer medicines the overall spending on cancer care has remained stable at around six percent of total health expenditure largely due to a shift towards outpatient care. The report also concludes that there is great difference in access to medicines, in particular between richer and poorer countries but also between countries with similar purchasing power. The access problem requires collaboration between policy makers, payers, regulators, HTA bodies and manufacturers. Local solutions seem most feasible to balance the risk and reward of new treatment options between payers and manufacturers and reflect the affordability levels of different countries.
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| 7. |
- Jönsson, Bengt, et al.
(författare)
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Comparator Report on Patient Access to Cancer Medicines in Europe Revisited - A UK Perspective
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- IHE has published a new comparator report on the cost of cancer and access to cancer medicines. The report is a condensed version of the previously published report, Comparator report on patient access to cancer medicines in Europe revisited (IHE Report 2016:4) and focusing on the UK.The report reveals similar trends in the UK as in the rest of Europe: incidence of cancer is increasing, as is mortality in absolute terms but once demographic factors is accounted for mortality has decreased due to increased survival. However, compared to countries with similar economic status the UK lags behind.
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| 8. |
- Jönsson, Bengt, et al.
(författare)
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Får norska cancerpatienter den behandling de förtjänar?
- 2006
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Ingår i: Tidsskrift for den Norske Lægeforening. - : Norwegian Medical Assocation. - 0807-7096 .- 0029-2001. ; 126:21, s. 2828-2829
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- För de patienter som idag insjuknar med cancer, är skillnaden mellan tidigt och sent användande av nya förbättrade läkemedel skillnaden mellan att få eller inte få chansen till optimal behandling. Norska cancerpatienter må ha tillgång till modern cancerbehandling på samma sätt som andra patienter har inom stora delar av Europa.
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| 9. |
- Jönsson, Bengt, et al.
(författare)
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The cost and burden of cancer in the European Union 1995–2014
- 2016
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 66, s. 162-170
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is an intense debate about the cost of cancer and the value of new treatments. However, there is limited data on the cost of cancer in the European Union (EU) and how costs relate to the burden of disease. This paper presents new estimates on the development of the cost of cancer in the EU 1995–2014, with a focus on the major cost components: total health expenditure, cancer drugs, and production loss due to premature mortality.Methods: Data on overall health expenditure were combined with national disease estimates to derive cancer-specific health expenditure. Data on drug sales were obtained from IMS Health, and epidemiological data were used to calculate life years lost due to cancer.Findings: Health expenditure on cancer increased continuously from €35.7 billion in 1995 to €83.2 billion in 2014 in the EU and spending on cancer drugs from €7.6 billion in 2005 to €19.1 billion in 2014 (current prices). Yet the share of total health expenditure devoted to cancer was mostly constant (around 6 per cent). While expenditures on cancer drugs increased in both absolute and relative terms, other expenditures were stable or decreased, despite increases in cancer incidence driven by a growing and ageing population. Reductions in cancer mortality during working age resulted in decreasing production loss due to premature mortality.Interpretation: Health spending on cancer as a share of total health expenditure is rather low and stable despite the growing incidence and relative burden of cancer. Problems to reallocate funding in health care systems under economic pressure may be one explanation and shifting costs from inpatient to ambulatory care another.
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| 10. |
- Laakso, Mervi, et al.
(författare)
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Basoluminal carcinoma: A new biologically and prognostically distinct entity between basal and luminal breast cancer
- 2006
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 12:14, s. 4185-4191
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Breast carcinomas expressing basal epithelium cytokeratins constitute a tumor subgroup that is typically hormone receptor negative and shows a distinct gene expression profile. Based on variable basal cytokeratin immunostaining patterns, we hypothesized that the "basal phenotype" tumor group may comprise more than one biological entity. Experimental Design: Basal cytokeratins 5 and 14 (CK5/14) were stained by immunohistochemistry and the percentage of positive cells was defined by image analysis. The results thus obtained were compared with clinicopathologic characteristics and relapse-free survival. Results: Of the 506 breast tumors, 53 (10.5%) showed immunoreactivity for CK5/14. Basal cytokeratin expression showed up as two microscopically distinguishable subtypes, i.e., a uniformly positive type ("basal") and a partially positive type ("basoluminal") often displaying a checkerboard-type intratumoral heterogeneity. These subgroups could also be separated with a third basal cytokeratin (CK17, P < 0,0001). Both basal and basoluminal subtypes were hormone receptor negative and of high grade, but differed with respect to the Ki-67 labeling index (P = 0.0014), vimentin (P = 0.005), and c-kit (P = 0.02), which were more frequently expressed in basal than in basoluminal tumors. In contrast, the amplification of HER-2 was found almost exclusively in the basoluminal subgroup (P = 0.009). Compared with the basal tumors, basoluminal tumors associated with significantly shorter relapse-free survival (P = 0.01), which was not explained by their more frequent HER-2 amplification. Conclusions: We conclude that the intratumoral heterogeneity in basal cytokeratin expression can be used to define two distinct breast cancer subtypes, basal and basoluminal, with distinctive features related to proliferation activity, oncogene and biomarker status, and patient survival.
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| 11. |
- Lawler, Mark, et al.
(författare)
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A Catalyst for Change: The European Cancer Patient's Bill of Rights.
- 2014
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Ingår i: The Oncologist. - : Oxford University Press (OUP). - 1549-490X .- 1083-7159.
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Tidskriftsartikel (refereegranskat)abstract
- The European Cancer Concord is a unique patient-centered partnership that will act as a catalyst to achieve improved access to an optimal standard of cancer care and research for European citizens. In order to provide tangible benefits for European cancer patients, the partnership proposes the creation of a “European Cancer Patient's Bill of Rights,” a patient charter that will underpin equitable access to an optimal standard of care for Europe's citizens.
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| 12. |
- Linderholm, B. K., et al.
(författare)
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Angiogenic factors in relation to clinical effect in a phase II trial of weekly paclitaxel
- 2013
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Ingår i: Breast. - : Elsevier BV. - 1532-3080. ; 22:6, s. 1142-1147
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several anticancer agents including paclitaxel have an inhibitory effect on angiogenesis. Aims: To compare the overall response rate and time to progression with changes in circulating angiogenic factors during palliative treatment with weekly paclitaxel. Material and methods: Patients with metastatic BC, ECOG 0-2, received weekly paclitaxel, concomitant with trastuzumab if HER2+ BC (n = 7). Circulating vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were determined at base-line and before start of new course. Results: Fifty-five of 63 included patients were evaluable. The overall response rate including stable disease >= 24 weeks (CR + PD + SD) was obtained in 25 of the evaluable patients (45%). The median time to progression (TTP) was 5.3 months and overall survival (OS) 16.7 months. Patients with triple negative breast cancer (TNBC) showed a trend towards higher base-line VEGF compared with hormone receptor positive or HER2+ tumours and had shorter TTP. Significant differences in VEGF and bFGF levels at 12 weeks were found between patients with longer versus shorter TTP (VEGF: p = 0.046, bFGF: p = 0.005) and between patients gaining versus lacking clinical benefit (VEGF: p = 0.05, bFGF: p = 0.02). Conclusions: The clinical utility of circulating VEGF may be a useful tool for monitoring treatment efficacy. (C) 2013 Elsevier Ltd. All rights reserved.
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| 13. |
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| 14. |
- Lundkvist, Jonas, et al.
(författare)
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Cost-effectiveness of exemestane versus tamoxifen as adjuvant therapy for early-stage breast cancer after 2-3 years treatment with tamoxifen in Sweden.
- 2007
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Ingår i: Breast cancer research and treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 102:3, s. 289-99
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Tidskriftsartikel (refereegranskat)abstract
- Aromatase inhibitors are rapidly becoming the cornerstone of endocrine treatment for advanced disease and are now also used as adjuvant treatment in early-stage disease. The objective of this study was to assess the cost-effectiveness of adjuvant treatment with exemestane versus tamoxifen for early-stage breast cancer after 2-3 years treatment with tamoxifen in Sweden.The results are based on findings in the Intergroup Exemestane Study (IES). IES was a randomized controlled trial in which postmenopausal women who had received 2-3 years of tamoxifen therapy following primary treatment of early-stage breast cancer, were randomized to either continue on tamoxifen therapy or be switched to exemestane therapy. The results showed a disease-free survival hazard ratio of exemestane relative to tamoxifen in IES of 0.69. A Markov state-transition model was developed to simulate consequences after the end of the clinical trial, and to integrate the trial data with external data on mortality, costs and quality of life specific for Swedish women.The cost per QALY gained was about euro 20,000 in the base case analysis without inclusion of consequences of coronary heart disease. Inclusion of these events increased the cost-effectiveness ratio to about euro 31,000. This means that, based on our assumption, sequential exemestane treatment in early breast cancer is a cost-effective option compared with tamoxifen alone, although more long-term data on overall survival and consequences of adverse events would be valuable to increase the validity of the analysis further.
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| 15. |
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| 16. |
- Palmebäck Wegman, Pia, 1964-
(författare)
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Studies of tamoxifen resistance in breast cancer
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Oestrogen is one of the most important hormonal regulators and is known to play a key role in the development and growth of breast cancer. The majority of tumours have a hormone dependent growth, and this is indicated by the presence of oestrogen receptors (ERs). About two thirds of breast cancers occur after the menopause when the ovaries have ceased to produce oestrogen and despite the low levels of circulating oestrogen’s the tumour concentrations of oestrone, oestradiol and their sulfates have been shown to be significant. Patients with hormone dependent tumours are candidates for treatment with the anti-oestrogen tamoxifen, which acts by competing with oestrogen for binding to the ER thereby, diminish the transcription of oestrogen regulated genes. The drug is mainly metabolised by cytochrome P450 enzymes in the liver and to a lesser extent locally in the breast, where upon several produced metabolites have higher affinity for the ER than the mother substance. Patients treated with tamoxifen have in general a prolonged disease-free survival. Even if most patients respond well to tamoxifen about 30-50 % either fail to respond or become resistant by incompletely understood mechanisms. Therefore, the aim of this thesis was to investigate possible mechanisms responsible for tamoxifen resistance. In paper I and II we studied genetic variants of enzymes participating in the metabolism of tamoxifen and assessed whether these variants correlated to breast cancer prognosis and/or to the benefit of tamoxifen. The results indicate an influence of CYP2D6, CYP3A5, and SULT1A1 genotypes in tamoxifen response. Further, tamoxifen has shown to compete with oestrogen for the binding to ER. In paper III we measured the expression levels of enzymes involved in the local synthesis of oestrogens in order to see if they correlated to clinical outcome. The protein expression of stromal aromatase was shown to have a prognostic significance, especially in ER-positive patients. Finally, tamoxifen and its ER-active metabolites have shown to induce both cell cycle arrest and apoptosis and one central mediator in these processes is the tumour suppressor protein p53. The proapoptotic activity of p53 is dependent on a proline rich domain containing a common Pro-to-Arg polymorphism. In paper IV we examined the value of this genetic variant as a predictive marker for anti-cancer therapy and found that patients carrying the Pro-allele might be good responders of tamoxifen therapy. The present thesis further indicates the complexity of the mechanisms underlying tamoxifen resistance. In summary, genetic variants of metabolic enzymes, genetic variants in p53, as well as expression levels of enzymes involved in local oestrogen synthesis, may have influence on breast cancer prognosis and may be useful markers in the prediction of tamoxifen response.
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| 17. |
- Ringborg, Ulrik, et al.
(författare)
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The Porto European Cancer Research Summit 2021
- 2021
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 15:10, s. 2507-2543
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Tidskriftsartikel (refereegranskat)abstract
- Key stakeholders from the cancer research continuum met in May 2021 at the European Cancer Research Summit in Porto to discuss priorities and specific action points required for the successful implementation of the European Cancer Mission and Europe's Beating Cancer Plan (EBCP). Speakers presented a unified view about the need to establish high-quality, networked infrastructures to decrease cancer incidence, increase the cure rate, improve patient's survival and quality of life, and deal with research and care inequalities across the European Union (EU). These infrastructures, featuring Comprehensive Cancer Centres (CCCs) as key components, will integrate care, prevention and research across the entire cancer continuum to support the development of personalized/precision cancer medicine in Europe. The three pillars of the recommended European infrastructures – namely translational research, clinical/prevention trials and outcomes research – were pondered at length. Speakers addressing the future needs of translational research focused on the prospects of multiomics assisted preclinical research, progress in Molecular and Digital Pathology, immunotherapy, liquid biopsy and science data. The clinical/prevention trial session presented the requirements for next-generation, multicentric trials entailing unified strategies for patient stratification, imaging, and biospecimen acquisition and storage. The third session highlighted the need for establishing outcomes research infrastructures to cover primary prevention, early detection, clinical effectiveness of innovations, health-related quality-of-life assessment, survivorship research and health economics. An important outcome of the Summit was the presentation of the Porto Declaration, which called for a collective and committed action throughout Europe to develop the cancer research infrastructures indispensable for fostering innovation and decreasing inequalities within and between member states. Moreover, the Summit guidelines will assist decision making in the context of a unique EU-wide cancer initiative that, if expertly implemented, will decrease the cancer death toll and improve the quality of life of those confronted with cancer, and this is carried out at an affordable cost.
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| 18. |
- Salgado, Roberto, et al.
(författare)
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Societal challenges of precision medicine : Bringing order to chaos
- 2017
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 84, s. 325-334
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Tidskriftsartikel (refereegranskat)abstract
- The increasing number of drugs targeting specific proteins implicated in tumourigenesis and the commercial promotion of relatively affordable genome-wide analyses has led to an increasing expectation among patients with cancer that they can now receive effective personalised treatment based on the often complex genomic signature of their tumour. For such approaches to work in routine practice, the development of correspondingly complex biomarker assays through an appropriate and rigorous regulatory framework will be required. It is becoming increasingly evident that a re-engineering of clinical research is necessary so that regulatory considerations and procedures facilitate the efficient translation of these required biomarker assays from the discovery setting through to clinical application. This article discusses the practical requirements and challenges of developing such new precision medicine strategies, based on leveraging complex genomic profiles, as discussed at the Innovation and Biomarkers in Cancer Drug Development meeting (8th–9th September 2016, Brussels, Belgium).
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| 19. |
- Sundquist, Marie
(författare)
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Prognostic Factors in Breast Cancer
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer is increasing in the industrialised countries. Due to early detection and adjuvaut treatment with radiotherapy, hormones and chemotherapy, mortality has decreased. The different adjuvant treatments have adverse effects. It is an important task is to estimate the risk of recurrence for the individual patient in order to tailor her individual treatment. This thesis aims at identifying predictors for disease development in primary and disseminated breast cancer.Histologic grade was strongly correlated to breast cancer mortality in 630 patients with primary breast cancer. The combination of grade, tumour size and lymph node status in the Nottingham Prognostic Index provides a powerful instrument separating patients in groups with excellent, good, intermediate and poor prognosis.Grade was more sensitive than S-phase fraction in identifying high risk patients and patients with very good prognosis.Presence of cancer cells in blood- and lymph vessels close to the tumour in patients with grade 3 tumours increased the risk oflocoregional recurrence 6-fold as compared to patients with grade 1 or 2 tumours without such vascular invasion.The mortality of young women with breast cancer has decreased very little since 1960. Women under 37 years of age had increased tumour size, more metastatic lymph nodes and doubled rate of high grade tumours as compared to older women.Disease-free interval and survival in patients with distant recurrence were strongly associated to histologic grade and hormone receptor content. Patients with grade 3, hormone receptor negative tumours had a median survival of 10 months after recurrence while only 15 % of women with receptor positive, grade 1 tumours have so far died after a median follow-up time of 5 years after recurrence.The Nottingham Prognostic Index and assessments of presence of tmnour cells in vessels provide important information about the risk oflocoregional and distant recurrence in breast cancer. Treatment decisions, counselling and follow-up programmes should be based on such assessments. For patients with metastatic breast cancer, tumour grade, estrogen receptor status and serum-c-erbB-2 predict the course of the disease.
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| 20. |
- Söderqvist, Gunnar, et al.
(författare)
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Metabolism of estrone sulfate by normal breast tissue : Influence of menopausal status and oral contraceptives
- 1994
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Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760. ; 48:2-3, s. 221-224
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Tidskriftsartikel (refereegranskat)abstract
- The metabolism of [ 3 H]estrone sulfate ([ 3 H]E 1 S) was studied in normal breast tissue from 10 premenopausal women without oral contraceptives (OC), in 12 OC users and in 9 untreated postmenopausal women. [ 3 H]E 1 S was converted into estrone ([ 3 H]E 1 ) and estradiol-17β ([ 3 H]E 2 ) by tissue samples from all three groups of women, with only minor formation of other unconjugated compounds. The rate of [ 3 H]E 2 formation was significantly higher in premenopausal women without OC than in postmenopausal women. Among premenopausal women, OC users had a significantly lower rate of total hydrolysis and of [ 3 H]E 1 formation than non-users. The rate of total hydrolysis of [ 3 H]E 1 S in normal breast tissue from all three groups of women was similar to that in muscle, but the rate of [ 3 H]E 2 formation was ten times higher. Both total hydrolysis rate and rate of [ 3 H]E 2 formation were significantly lower in normal breast tissue than in breast carcinoma and in normal and neoplastic endometrium. The specific ability of normal breast tissue to convert E 1 S into the terminal biologically active estrogen E 2 may be important for estrogenic stimulation of the breast in subjects with low circulating E 2 levels. The lower rate of E 1 formation in OC users may reflect an inhibitory effect of the progestagen compound in such preparations.
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| 21. |
- Villman, Kenneth, 1958-
(författare)
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Chemosensitivity in Breast Cancer
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer mortality in Sweden is now in decline, thanks to early detection and the wide use of adjuvant endocrine therapy and chemotherapy. While hormone receptor status is predictive of response to endocrine treatment, there is no clinically useful predictive marker of a patient’s response to chemotherapy. Consequently, patients receive chemotherapy with considerable toxicity but minimal benefit. The aim of this thesis was to investigate a number of methods with the potential to predict response to chemotherapy and thus enhance treatment efficacy in breast cancer patients.We found that topo IIα, the key target enzyme of topo II inhibitors, is significantly expressed in nonproliferating breast cancer cells. This finding may explain why topo II inhibitors are effective in patients with slow growing tumors and a low proliferation rate.Topo IIα gene amplification was suggestive of increased response to anthracyclines in advanced breast cancer, whereas the oncogene HER2 had no predictive value by itself. These findings are in accordance with current knowledge.Cyclin A, a marker of cell proliferation, showed good prognostic value but did not predict response to chemotherapy in advanced breast cancer.In vitro chemosensitivity testing with FMCA predicted tumor response in patients with advanced breast cancer with a sensitivity of 89% and a specificity of 53%. Our results are consistent with the results from similar assays, which predict drug resistance with good accuracy while clinical drug sensitivity is less reliably predicted. The use of FMCA and similar assays is not yet recommended outside clinical trials; their main utility is in preclinical testing of new anti-cancer drugs, including targeted therapies.The combination of epirubicin, capecitabine, and cisplatin (EXC) demonstrated high clinical response rate (74%) and pathological complete response rate (22%) in locally advanced breast cancer, but with cumbersome toxicity. The fluoropyrimidine biomarkers TS, TP, and DPD did not predict response to the EXC regimen.
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| 22. |
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| 23. |
- Vrdoljak, E., et al.
(författare)
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Insights into cancer surveillance in Central and Eastern Europe, Israel and Turkey
- 2015
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Ingår i: European Journal of Cancer Care. - : Hindawi Limited. - 1365-2354 .- 0961-5423. ; 24:1, s. 99-110
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Tidskriftsartikel (refereegranskat)abstract
- The current cancer landscape within transitional economies in central and Eastern Europe and the Mediterranean area is not particularly optimistic. Current perceptions are often based on extrapolations from other countries and regions; and hence the authors collaborated with the South Eastern Europe Oncology Group (SEEROG) to collect information on cancer registration in Central and Eastern Europe, Israel and Turkey. Healthcare authorities and specialist oncology centres in 21 countries in the region were contacted for information on cancer registries in their countries. Based on this information, the authors believe that the recording and reporting of data on cancer in the region is at an acceptable level. The authors discuss and compare institution- and population-based registries, and present opinions on elements of an ideal registry' based on the survey replies and comparisons with other registries. A comparison with the sources used for GLOBOCAN 2008 illustrates the need for consistent data to be communicated, published and utilised throughout the region and the oncology community. The authors conclude by considering the potential value of collaboration between health authorities across the region, as well as between the clinical and epidemiological communities, to ensure that cancer data are consistently collected, verified and made public.
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| 24. |
- Wettermark, Björn, et al.
(författare)
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Forecasting drug utilization and expenditure in a metropolitan health region
- 2010
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Ingår i: BMC Health Services Research. - London, UK : BioMed Central. - 1472-6963. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: New pharmacological therapies are challenging the healthcare systems, and there is an increasing need to assess their therapeutic value in relation to existing alternatives as well as their potential budget impact. Consequently, new models to introduce drugs in healthcare are urgently needed. In the metropolitan health region of Stockholm, Sweden, a model has been developed including early warning (horizon scanning), forecasting of drug utilization and expenditure, critical drug evaluation as well as structured programs for the introduction and follow-up of new drugs. The aim of this paper is to present the forecasting model and the predicted growth in all therapeutic areas in 2010 and 2011.METHODS: Linear regression analysis was applied to aggregate sales data on hospital sales and dispensed drugs in ambulatory care, including both reimbursed expenditure and patient co-payment. The linear regression was applied on each pharmacological group based on four observations 2006-2009, and the crude predictions estimated for the coming two years 2010-2011. The crude predictions were then adjusted for factors likely to increase or decrease future utilization and expenditure, such as patent expiries, new drugs to be launched or new guidelines from national bodies or the regional Drug and Therapeutics Committee. The assessment included a close collaboration with clinical, clinical pharmacological and pharmaceutical experts from the regional Drug and Therapeutics Committee.RESULTS: The annual increase in total expenditure for prescription and hospital drugs was predicted to be 2.0% in 2010 and 4.0% in 2011. Expenditures will increase in most therapeutic areas, but most predominantly for antineoplastic and immune modulating agents as well as drugs for the nervous system, infectious diseases, and blood and blood-forming organs.CONCLUSIONS: The utilisation and expenditure of drugs is difficult to forecast due to uncertainties about the rate of adoption of new medicines and various ongoing healthcare reforms and activities to improve the quality and efficiency of prescribing. Nevertheless, we believe our model will be valuable as an early warning system to start developing guidance for new drugs including systems to monitor their effectiveness, safety and cost-effectiveness in clinical practice.
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