Skuteczność i koszty leczenia raka jajnika w Polsce – ujęcie regionalne

Ovarian cancer (OC) affects over 3 000 women in Poland annually. The efficacy of the therapy remains relatively low due to challenges of systematic improvement in the early detection OC rates. International comparisons indicate a positive correlation between health expenditures and 5-year survival rates of cancer patients. To the best of our knowledge, our study has been the first to present a correlation between the 5-year survival rates (SRs) and the cost of ovarian cancer therapy in particular regions of Poland. Material and methods: The study was based on the National Health Fund (NHF) data, available in the Disease Treatment Registry. The analysis included approximately 13 000 OC patients who started their treatment between 2005 and 2008 to allow for the evaluation of long-term therapy results. The 5-year survival rates were analyzed in relation to average NHF expenditures in various regions of Poland, distinguishing the population of patients aged 45-64 years. Results: The 5-year survival rate in the cohorts diagnosed in 2005 and 2008 changed marginally, from 42% to 43%, maintaining relatively large differences between the regions (from 35% to 53% in patients diagnosed in 2008). The NHF expenditures in particular regions differed significantly: mean cost for the entire treatment cycle ranged from 31.600 PLN do 58.000 PLN per person among patients diagnosed in 2008. No significant correlation between the survival and the cost was found. Conclusions: SRs of OC patients in particular regions of Poland are not correlated with average treatment cost. Thus, the differences in SRs between various regions of Poland have their source in other factors, e.g. clinical stage at diagnosis, or prevailing treatment patterns in the given region. Further studies may decrease regional discrepancies in patient care and SRs in OC subjects.Wstęp: W Polsce na raka jajnika zachorowuje corocznie ponad trzy tysiące kobiet. Ponieważ w praktyce trudno osiągnąć sytuację systematycznego, wczesnego wykrywania tej choroby, skuteczność jej leczenia jest relatywnie niska. Analiza danych zagranicznych pozwala stwierdzić występowanie korelacji wydatków na opiekę zdrowotną z 5-letnim przeżyciem pacjentów leczonych na chorobę nowotworową. W niniejszym opracowaniu, po raz pierwszy w Polsce, zbadano dane w ujęciu wojewódzkim, dotyczące 5-letniego przeżycia chorych na raka jajnika oraz wydatków na ich leczenie. Materiał i metody: W pracy wykorzystano dane pochodzące z Rejestru Leczenia Chorób Narodowego Funduszu Zdrowia. Analizie poddano blisko 13 tys. nowych potwierdzonych przypadków raka jajnika (początek leczenia w latach 2005–2008), aby umożliwić obserwację odległych wyników zastosowanej terapii. Dokonano analizy porównawczej wskaźników 5-letniego przeżycia oraz wydatków na leczenie w całym cyklu terapeutycznym, wyróżniając grupę pacjentek w wieku od 45 do 64 lat. Wyniki: Wartości wskaźników 5-letniego przeżycia pacjentek leczonych na raka jajnika wzrosły średnio w kohortach chorych, zdiagnozowanych w latach 2005–2008, z poziomu 42% do 43%, notując dużą rozpiętość w poszczególnych województwach (35%–53% w grupie pacjentek rozpoczynających leczenie w roku 2008). Znaczne różnice między województwami stwierdzono również w wydatkach na leczenie (31 tys.–58 tys. złotych na osobę w całym cyklu terapeutycznym, w grupie pacjentek rozpoczynających leczenie w roku 2008). Nie zaobserwowano jednak występowania, statystycznie istotnej, korelacji 5-letniego przeżycia chorych na raka jajnika z wydatkami na ich leczenie. Wnioski: Zestawienie wskaźników przeżycia 5-letniego w populacji chorych na raka jajnika ze średnimi wydatkami poszczególnych województw na ich leczenie nie wskazuje występowania istotnej statystycznie korelacji wydatków z efektami leczenia. Wobec tego przyczyn różnic występujących w wynikach leczenia należy szukać gdzie indziej. Być może wiążą się ze stopniem zaawansowania nowotworu w chwili rozpoczęcia leczenia lub z wyborem sposobu leczenia (treatment patterns). Pogłębienie tej analizy oraz identyfikacja i zrozumienie przyczyn występujących różnic mogą prowadzić do zmniejszenia regionalnych nierówności w zakresie wyników leczenia chorych na raka jajnika w Polsce

Reduction in the level of antibodies against heat shock proteins 60 during different hormonal protocols in postmenopausal women

Introduction: In current literature, the immune-inflammatory theory of atherosclerosis is widely discussed. The role of how heat shock proteins 60 (HSP60) lead to the development of the atheromatous plaque is especially underlined. The aim of the study is to estimate the influence of three hormonal protocols on behavior of antibodies against HSP60. It determines the state of endothelium in postmenopausal women. Material and methods: The study was carried out on 90 women between 2007 and 2012. All the women were in their menopausal age (51 ± 3 years), from the south region of Poland, with a follicle stimulating hormone (FSH) level above 25 mIU/ml, and with menopausal symptoms disturbing their normal daily activity. The study was done for a period of 6 months. Three groups of 30 randomized patients were formed. In the first group we used transdermal estrogen therapy in a 37.5 µg/24 h dose combined with a 10 mg dose of dydrogesterone. In the second group we applied transdermal estrogen therapy in a 50 µg/24 h dose with 2.5 mg of oral medroxyprogesterone. In both these groups, gestagens were administered continuously. In the third group, we prescribed continuous, oral, low-dose combined estrogen-gestagen therapy with 1 mg of ethinyl estradiol and 0.5 mg of norethisterone acetate. The control group consisted of 30 volunteers who were also from the south region of Poland, in good health, with menopausal symptoms, no menstrual period for the last 12 months, selected considering their age and weight, with an FSH level above 25 mIU/ml and with normal levels of thyroid stimulating hormone (TSH) and prolactin. All patients treated and in the control group were seronegative to Chlamydia pneumonia for the entire duration of the study. In the analysis conducted, nonparametric tests were used (Mann-Whitney U test, Wilcoxon test, Kruskal-Wallis test - ANOVA). Results: After 6 months of hormonal therapy, we found that all schemes of treatment promote a significant reduction in antibodies against HSP60 in all treated groups vs. the control group. Conclusions: All of the investigated estrogen protocols have a favorable impact on the blood level of HSP60 antibodies in early postmenopausal women who have no cardiovascular risk factors. It triggers a better condition of endothelium

ARTICLEAssociation of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival

Aim To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Methods Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09–1.56)]. Conclusion Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk

Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival

Background: Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers.Aim: To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS.Methods: Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results: There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy.Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09-1.56)].Conclusion: Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.Peer reviewe

Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element

A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30-to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 x 10(-31)).Peer reviewe

Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element.

A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10)

CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

Funder: Breast Cancer Now (BCN); doi: https://doi.org/10.13039/100009794Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265Funder: U.S. Department of Health & Human Services | National Institutes of Health (NIH)Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): HEALTH-F2-2009-223175, HEALTH-F2-2009-223175Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada); doi: https://doi.org/10.13039/501100000024Funder: Quebec Breast cancer Foundation Genome QuebecFunder: U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM); doi: https://doi.org/10.13039/100000092Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))Funder: European Union’s Horizon 2020Funder: Deutsche Krebshilfe (German Cancer Aid); doi: https://doi.org/10.13039/501100005972Funder: BCAST - European Union’s Horizon 2020Funder: Breast Cancer Now; doi: https://doi.org/10.13039/501100007913Abstract: Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Results: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (−49.2%, 95% CI −56.1% to −41.1%, P = 3.1 × 10–18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (−26.7%, 95% CI −39.4% to −11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82–0.91, P = 6.9 × 10–8). Conclusions: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women

Skuteczność i koszty leczenia raka jajnika w Polsce; podejście regionalne

Ovarian cancer (OC) affects over 3 000 women in Poland annually. The efficacy of the therapy remains relatively low due to challenges of systematic improvement in the early detection OC rates. International comparisons indicate a positive correlation between health expenditures and 5-year survival rates of cancer patients. To the best of our knowledge, our study has been the first to present a correlation between the 5-year survival rates (SRs) and the cost of ovarian cancer therapy in particular regions of Poland. Material and methods: The study was based on the National Health Fund (NHF) data, available in the Disease Treatment Registry. The analysis included approximately 13 000 OC patients who started their treatment between 2005 and 2008 to allow for the evaluation of long-term therapy results. The 5-year survival rates were analyzed in relation to average NHF expenditures in various regions of Poland, distinguishing the population of patients aged 45-64 years. Results: The 5-year survival rate in the cohorts diagnosed in 2005 and 2008 changed marginally, from 42% to 43%, maintaining relatively large differences between the regions (from 35% to 53% in patients diagnosed in 2008). The NHF expenditures in particular regions differed significantly: mean cost for the entire treatment cycle ranged from 31.600 PLN do 58.000 PLN per person among patients diagnosed in 2008. No significant correlation between the survival and the cost was found. Conclusions: SRs of OC patients in particular regions of Poland are not correlated with average treatment cost. Thus, the differences in SRs between various regions of Poland have their source in other factors, e.g. clinical stage at diagnosis, or prevailing treatment patterns in the given region. Further studies may decrease regional discrepancies in patient care and SRs in OC subjects.Wstęp: W Polsce na raka jajnika zachorowuje corocznie ponad trzy tysiące kobiet. Ponieważ w praktyce trudno osiągnąć sytuację systematycznego, wczesnego wykrywania tej choroby, skuteczność jej leczenia jest relatywnie niska. Analiza danych zagranicznych pozwala stwierdzić występowanie korelacji wydatków na opiekę zdrowotną z 5-letnim przeżyciem pacjentów leczonych na chorobę nowotworową. W niniejszym opracowaniu, po raz pierwszy w Polsce, zbadano dane w ujęciu wojewódzkim, dotyczące 5-letniego przeżycia chorych na raka jajnika oraz wydatków na ich leczenie. Materiał i metody: W pracy wykorzystano dane pochodzące z Rejestru Leczenia Chorób Narodowego Funduszu Zdrowia. Analizie poddano blisko 13 tys. nowych potwierdzonych przypadków raka jajnika (początek leczenia w latach 2005–2008), aby umożliwić obserwację odległych wyników zastosowanej terapii. Dokonano analizy porównawczej wskaźników 5-letniego przeżycia oraz wydatków na leczenie w całym cyklu terapeutycznym, wyróżniając grupę pacjentek w wieku od 45 do 64 lat. Wyniki: Wartości wskaźników 5-letniego przeżycia pacjentek leczonych na raka jajnika wzrosły średnio w kohortach chorych, zdiagnozowanych w latach 2005–2008, z poziomu 42% do 43%, notując dużą rozpiętość w poszczególnych województwach (35%–53% w grupie pacjentek rozpoczynających leczenie w roku 2008). Znaczne różnice między województwami stwierdzono również w wydatkach na leczenie (31 tys.–58 tys. złotych na osobę w całym cyklu terapeutycznym, w grupie pacjentek rozpoczynających leczenie w roku 2008). Nie zaobserwowano jednak występowania, statystycznie istotnej, korelacji 5-letniego przeżycia chorych na raka jajnika z wydatkami na ich leczenie. Wnioski: Zestawienie wskaźników przeżycia 5-letniego w populacji chorych na raka jajnika ze średnimi wydatkami poszczególnych województw na ich leczenie nie wskazuje występowania istotnej statystycznie korelacji wydatków z efektami leczenia. Wobec tego przyczyn różnic występujących w wynikach leczenia należy szukać gdzie indziej. Być może wiążą się ze stopniem zaawansowania nowotworu w chwili rozpoczęcia leczenia lub z wyborem sposobu leczenia (treatment patterns). Pogłębienie tej analizy oraz identyfikacja i zrozumienie przyczyn występujących różnic mogą prowadzić do zmniejszenia regionalnych nierówności w zakresie wyników leczenia chorych na raka jajnika w Polsce