A multipurpose TNM stage ontology for cancer registries.

BACKGROUND: Population-based cancer registries are a critical reference source for the surveillance and control of cancer. Cancer registries work extensively with the internationally recognised TNM classification system used to stage solid tumours, but the system is complex and compounded by the different TNM editions in concurrent use. TNM ontologies exist but the design requirements are different for the needs of the clinical and cancer-registry domains. Two TNM ontologies developed specifically for cancer registries were designed for different purposes and have limitations for serving wider application. A unified ontology is proposed to serve the various cancer registry TNM-related tasks and reduce the multiplication effects of different ontologies serving specific tasks. The ontology is comprehensive of the rules for TNM edition 7 as required by cancer registries and designed on a modular basis to allow extension to other TNM editions. RESULTS: A unified ontology was developed building on the experience and design of the existing ontologies. It follows a modular approach allowing plug in of components dependent upon any particular TNM edition. A Java front-end was developed to interface with the ontology via the Web Ontology Language application programme interface and enables batch validation or classification of cancer registry records. The programme also allows the means of automated error correction in some instances. Initial tests verified the design concept by correctly inferring TNM stage and successfully handling the TNM-related validation checks on a number of cancer case records, with a performance similar to that of an existing ontology dedicated to the task. CONCLUSIONS: The unified ontology provides a multi-purpose tool for TNM-related tasks in a cancer registry and is scalable for different editions of TNM. It offers a convenient way of quickly checking validity of cancer case stage information and for batch processing of multi-record data via a dedicated front-end programme. The ontology is adaptable to many uses, either as a standalone TNM module or as a component in applications of wider focus. It provides a first step towards a single, unified TNM ontology for cancer registries.

Impact of the first wave of the COVID-19 pandemic on cancer registration and cancer care: a European survey.

BACKGROUND: The coronavirus disease COVID-19 pandemic posed a number of challenges to the oncology community, particularly the diagnosis and care of cancer patients while ensuring safety from the virus for both patients and professionals: minimization of visits to the hospital, cancellation of the screening programmes and the difficulties in the management and operation of cancer registries (CRs) while working remotely. This article describes the effects in the medium term of the first wave of the COVID-19 pandemic on cancer registration in Europe, focusing on changes in cancer detection and treatment, possible reduction of CR resources and difficulties in the access to data sources. METHODS: A questionnaire was distributed in June 2020 to the directors of 108 CRs from 34 countries affiliated to the European Network of Cancer Registries, providing a 37% response rate. RESULTS: The results of the survey showed that cancer-screening programmes were mostly stopped or slowed down in the majority of regions covered by the respondent CRs. Cancer diagnostics and treatments were severely disrupted. The cancer registration process was also disrupted, due to changes in the work modalities for the personnel, as well as to the difficulties in accessing sources and/or receiving the notifications. In some CRs, staff was allocated to different activities related to controlling the pandemic. Several CRs reported that they were investigating the impact of COVID-19 on cancer care via dedicated studies. CONCLUSIONS: A careful analysis will be necessary for proper interpretation of temporal and geographical variations of the 2020 cancer burden indicators.

The European cancer burden in 2020: Incidence and mortality estimates for 40 countries and 25 major cancers.

INTRODUCTION: Europe is an important focus for compiling accurate and up-to-date world cancer statistics owing to its large share of the world's total cancer burden. This article presents incidence and mortality estimates for 25 major cancers across 40 individual countries within European areas and the European Union (EU-27) for the year 2020. METHODS: The estimated national incidence and mortality rates are based on statistical methodology previously applied and verified using the most recently collected incidence data from 151 population-based cancer registries, mortality data and 2020 population estimates. RESULTS: Estimates reveal 4 million new cases of cancer (excluding non-melanoma skin cancer) and 1.9 million cancer-related deaths. The most common cancers are: breast in women (530,000 cases), colorectum (520,000), lung (480,000) and prostate (470,000). These four cancers account for half the overall cancer burden in Europe. The most common causes of cancer deaths are: lung (380,000), colorectal (250,000), breast (140,000) and pancreatic (130,000) cancers. In EU-27, the estimated new cancer cases are approximately 1.4 million in males and 1.2 million in females, with over 710,000 estimated cancer deaths in males and 560,000 in females. CONCLUSION: The 2020 estimates provide a basis for establishing priorities in cancer-control measures across Europe. The long-established role of cancer registries in cancer surveillance and the evaluation of cancer control measures remain fundamental in formulating and adapting national cancer plans and pan-European health policies. Given the estimates are built on recorded data prior to the onset of coronavirus disease 2019 (COVID-19), they do not take into account the impact of the pandemic.

An ontology-based approach for developing a harmonised data-validation tool for European cancer registration.

BACKGROUND: Population-based cancer registries constitute an important information source in cancer epidemiology. Studies collating and comparing data across regional and national boundaries have proved important for deploying and evaluating effective cancer-control strategies. A critical aspect in correctly comparing cancer indicators across regional and national boundaries lies in ensuring a good and harmonised level of data quality, which is a primary motivator for a centralised collection of pseudonymised data. The recent introduction of the European Union's general data-protection regulation (GDPR) imposes stricter conditions on the collection, processing, and sharing of personal data. It also considers pseudonymised data as personal data. The new regulation motivates the need to find solutions that allow a continuation of the smooth processes leading to harmonised European cancer-registry data. One element in this regard would be the availability of a data-validation software tool based on a formalised depiction of the harmonised data-validation rules, allowing an eventual devolution of the data-validation process to the local level. RESULTS: A semantic data model was derived from the data-validation rules for harmonising cancer-data variables at European level. The data model was encapsulated in an ontology developed using the Web-Ontology Language (OWL) with the data-model entities forming the main OWL classes. The data-validation rules were added as axioms in the ontology. The reasoning function of the resulting ontology demonstrated its ability to trap registry-coding errors and in some instances to be able to correct errors. CONCLUSIONS: Describing the European cancer-registry core data set in terms of an OWL ontology affords a tool based on a formalised set of axioms for validating a cancer-registry's data set according to harmonised, supra-national rules. The fact that the data checks are inherently linked to the data model would lead to less maintenance overheads and also allow automatic versioning synchronisation, important for distributed data-quality checking processes.

Cancer registries - guardians of breast cancer biomarker information: A systematic review.

BACKGROUND: Breast cancer is the most common cancer and the leading cause of cancer-related death in females, with a large societal and economic impact. Decisions regarding its treatment are largely affected by the categorization into different subtypes with hormone receptor status and HER2 status being the most important predictive factors. Other biological markers play an important role for prognostic and predictive reasons. The data collection and harmonization of cancer cases are performed by cancer registries whose collection of parameters largely differs, partially including results from biomarker testing. METHODS: This systematic literature review consisting of a total of 729 reports determined whether information about biomarker testing in breast cancer cases is collected and published by cancer registries worldwide. RESULTS: The number of publications using breast cancer biomarker data from registries steeply rose with the beginning of the 21st century and some hospital-based and population-based cancer registries reacted with immediate collection of biomarker data following the recommendation of clinical guidelines. For female breast cancer, biomarkers have achieved an essential clinical value and this review points to a steady increase in the collection of biomarker data by cancer registries during the last decade. CONCLUSIONS: In the future, recommendations for biomarker data collection and coding by cancer registries may be required to ensure harmonization and comparability of the data.

Early quality-of-life and psychological predictors of disease-free time and survival in localized prostate cancer.

PURPOSE: The constructs evaluated in investigating association between psychosocial factors and cancer survival has varied between studies, and factors related to quality of life (QOL) have shown contradictory results. We investigated the effect of socioeconomic and early QOL and psychological factors on disease-free time and survival in localized prostate cancer. METHODS: A consecutive sample of patients with localized prostate cancer (T1-3, N0, M0) treated with external beam radiotherapy completed validated questionnaires on coping with cancer (the Ways of Coping Questionnaire WOC-CA), anger expression (the Anger Expression Scale), life events (the Life Experience Survey), and various aspects of QOL (the Rotterdam Symptom Checklist, the Depression Scale DEPS, the EORTC QLQ-C30, the LENT-SOMA outcome measure) approximately 4.5 months after diagnosis. Cox regression analyses were used to determine the predictors of the disease-free and overall survival times measured from the date of diagnosis to the date of a PSA-relapse and date of death. RESULTS: After controlling for biological prognostic factors, age, and adjuvant hormonal therapies, moderate and high socioeconomic status and an increased level of pain predicted longer survival, whereas an increased level of prostate-area symptoms and fatigue and, especially, reports of no/few physical symptoms were predictors of a shorter survival time. A longer PSA-relapse-free time was predicted by Cognitive Avoidance/Denial coping, whereas problems in social functioning, hopelessness, and an excellent self-reported QOL predicted a shorter PSA-relapse-free time. CONCLUSIONS: Higher socioeconomic status was prognostic for longer survival, as previously reported. Patients with a seemingly good QOL (few physical complaints, excellent self-reported QOL) had poorer prognoses. This association may due to the survival decreasing effect of emotional non-expression; patients with high emotional non-expression may over-report their wellbeing in simple measures, and thus actually be in need of extra attention and care.

Variability of cancer risk within an area: time to complement the incidence rate.

The aim of this study was to show that age-adjusted cancer incidence rates for an area may not be representative of the incidence in subareas. We propose a simple measure to show the amount of geographical variability. European age-standardized incidence rates (ASRs) for 'all sites excluding nonmelanoma skin cancer', for men, in 2014, for Nordic countries as a whole, for each country (Denmark, Faroe Islands, Finland, Greenland, Iceland, Sweden and Norway) and for their regions, were retrieved from the Nordcan with corresponding standard errors SEs. We compared the ASR for Nordic countries versus single country and single country versus specific regions. The overlapping of 95% confidence intervals was used for ASRs comparisons. As a measure of variability, we computed the range between the highest and the lowest ASR within an area and the ratio between this range and the ASR of the overall area, r/R=(range/ASR)×100. The 95% confidence interval of the ASR for Nordic countries as a whole did not overlap those of the majority of the single countries; in fact, the r/R - which provides a clue for the amount of underlying geographical variability - was rather large (57.1%). Within countries, the variability was negligible in Iceland (r/R=9.6%), whereas the highest value was found in Sweden (37.1%). The ASR does not provide any information on underlying geographical variability. Therefore, its interpretation could be misleading. When data for subareas are available, the r/R, which is simple to compute and to understand, should be added to the ASR for providing more truthful information.

Pain Sensation During Colposcopy and Cervical Biopsy, With or Without Local Anesthesia: A Randomized Trial.

OBJECTIVE: The aim of the study was to determine whether an injection of a local anesthetic is more painful than a cervical punch biopsy without local anesthesia. MATERIALS AND METHODS: The study was a randomized controlled trial, conducted at the Helsinki University Central Hospital. It consisted of 204 women referred for colposcopic assessments. Half of them were randomized to receive local anesthesia before their cervical punch biopsies. After the injection of the local anesthetic, the cervical punch biopsy, and the endocervical curettage, the women scored their actual pain using a 10-cm visual analog scale (VAS).To measure the difference in VAS scores between two groups, a linear regression model was used. Binomial regression model was applied for comparing the probability of experiencing unbearable pain between the groups. Applying modeling approach allowed also for proper adjustment for other potential risk factors. RESULTS: The mean VAS score for the injection of the local anesthetic was 2.7, the VAS score for the cervical punch biopsy without local anesthesia was 3.5, and the difference was 0.8 (p = .017; 95% CI = 0.1-1.5). The mean VAS for the biopsy with local anesthesia was 0.8, which was significantly lower than the mean VAS for the biopsy without local anesthesia (difference = 2.7; p < .001; 95% CI = 2.2-3.3). The relative risk for experiencing moderate or severe pain (VAS ≥ 5) was 0.6 (p = .03; 95% CI = 0.3-0.9) for the injection of local anesthetic versus the biopsy without local anesthesia. CONCLUSIONS: Injection of a local anesthetic for colposcopy is less painful than biopsies without local anesthesia, and local anesthesia decreases the pain perceived.

Performance of mRNA- and DNA-based high-risk human papillomavirus assays in detection of high-grade cervical lesions.

INTRODUCTION: The aim was to assess the performance of two commercial assays for the detection of high-risk human papillomavirus (hrHPV): Aptima HPV Assay (Hologic, Inc., Marlborough, MA, USA) which detects mRNA of 14 different hrHPV types, and Hybrid Capture 2 HPV DNA test (HC2; Qiagen, Gaithersburg, MD, USA), which detects the DNA of 13 different hrHPV types. Test performance was compared in the settings of a standard colposcopy clinic, among the regular patient flow. MATERIAL AND METHODS: Two separate cervical cell samples for Aptima and HC2 testing were collected from women referred to colposcopy or a cervical follow-up visit. Altogether, 481 paired samples were analyzed and all positive samples were also tested using the Aptima HPV 16 18/45 Genotype Assay. Results from the two assays were compared directly and with stratification by histology and cytology from the same sampling visit. RESULTS: The overall agreement between HC2 and Aptima assays was 92.9% (Kappa coefficient of 0.855). The sensitivity and specificity of the assays in detecting CIN2+ were 92.5 and 58.2% for HC2, and 94.0 and 59.3% for Aptima, respectively. No significant differences between the assays were found (p-values >0.5). Both assays detected all CIN3 (n = 30) and carcinoma (n = 2) cases. CONCLUSIONS: The mRNA-based Aptima assay and the extensively studied DNA-based HC2 test performed equally well in detecting high-grade cervical lesions. Our data contribute to the growing evidence base indicating that the mRNA-based Aptima assay could be used for the triage of patients with HPV-associated cervical disease.

Contribution of changes in demography and in the risk factors to the predicted pattern of cancer mortality among Spanish women by 2022.

BACKGROUND: Changes in the burden of cancer mortality are expected to be observed among Spanish women. We predict those changes, in Spain, for breast cancer (BC), colorectal cancer (CRC), lung cancer (LC) and pancreatic cancer (PC) from 2013 to 2022. METHODS: Bayesian age-period-cohort modeling was used to perform projections of the cancer burden in 2013-2022, extrapolating the trend of cancer mortality data from 1998 to 2012. We assessed the time trends of the crude rates (CRs) during 1998-2012, and compared the number of cancer deaths between the periods 2008-2012 and 2018-2022 to assess the contribution of demographic changes and changes in the risk factors for cancer. RESULTS: During 1998-2012, CRs of cancer decreased for BC (0.3% per year) and increased for LC (4.7%), PC (2%) and CRC (0.7%). During 2013-2022, CRs might level off for CRC, whereas the time trends for the remaining cancers might continue at a similar pace. During 2018-2022, BC could be surpassed by CRC as the most frequent cause of cancer mortality among Spanish women, whereas LC could be the most common cause of cancer mortality among women aged 50-69 years (N/year=1960 for BC versus N/year=1981 for LC). Comparing 2018-2022 and 1998-2012, changes in the risk factors for cancer could contribute 37.93% and 18.36% to the burden of LC and PC, respectively, and demographic shifts - mainly due to ageing (19.27%) - will drive the burden of CRC. CONCLUSIONS: During 2018-2022, demographic changes (ageing) and changes in risk factors could have a different impact on the lifetime risk of cancer among Spanish women.

Selecting the minimum prediction base of historical data to perform 5-year predictions of the cancer burden: The GoF-optimal method.

BACKGROUND: Predicting the future burden of cancer is a key issue for health services planning, where a method for selecting the predictive model and the prediction base is a challenge. A method, named here Goodness-of-Fit optimal (GoF-optimal), is presented to determine the minimum prediction base of historical data to perform 5-year predictions of the number of new cancer cases or deaths. METHODS: An empirical ex-post evaluation exercise for cancer mortality data in Spain and cancer incidence in Finland using simple linear and log-linear Poisson models was performed. Prediction bases were considered within the time periods 1951-2006 in Spain and 1975-2007 in Finland, and then predictions were made for 37 and 33 single years in these periods, respectively. The performance of three fixed different prediction bases (last 5, 10, and 20 years of historical data) was compared to that of the prediction base determined by the GoF-optimal method. The coverage (COV) of the 95% prediction interval and the discrepancy ratio (DR) were calculated to assess the success of the prediction. RESULTS: The results showed that (i) models using the prediction base selected through GoF-optimal method reached the highest COV and the lowest DR and (ii) the best alternative strategy to GoF-optimal was the one using the base of prediction of 5-years. CONCLUSIONS: The GoF-optimal approach can be used as a selection criterion in order to find an adequate base of prediction.

Postmenopausal hormone therapy-also use of estradiol plus levonorgestrel-intrauterine system is associated with an increased risk of primary fallopian tube carcinoma.

Data on the possible impact of postmenopausal hormone therapy (HT) on the incidence of rare primary fallopian tube carcinoma (PFTC) are scarce. Therefore, we conducted a nationwide case-control study analyzing the association between the use of different HTs and PFTC. All women aged 50 years or older with an incident PFTC (n = 360) during 1995-2007 were identified from the Finnish Cancer Registry. For each case of PFTC, ten age- and place of residence-matched controls were selected from the Finnish National Population Register, which also provided information on parity. Data on HT purchases were received from the Prescription Register, and data on hysterectomies and sterilizations from the National Care Register. Controls with a salpingectomy before the PFTC diagnosis of the respective case were excluded. The PFTC risk in relation to different HTs was estimated with a conditional logistic regression model, adjusted for parity, age at last delivery, hysterectomy and sterilization. The use for five years or more of estradiol combined with levonorgestrel-releasing-intrauterine system (odds ratio 2.84, 95% confidence interval 1.10-7.38) and sequential estradiol-progestin therapy (EPT; 3.37; 2.23-5.08) were both linked with increases in the risk of PFTC, while the risk with use of estradiol-only therapy or continuous EPT was not statistically significantly increased. The OR for the use of tibolone for one year or more was 1.56 (0.55-4.41). The use of HT is related to an increased risk of PFTC, particularly when a progestin component is intrauterine or systemic progestin is given in sequential manner.

Pregnancy incidence and outcome before and after cervical intraepithelial neoplasia: a retrospective cohort study.

We performed a retrospective cohort study of 3530 women treated for cervical intraepithelial neoplasia (CIN) in Helsinki University Central Hospital, Finland, to investigate whether CIN treatment itself affects pregnancy incidence and outcome. We estimated the incidence of live births, miscarriages, extrauterine pregnancies, molar pregnancies, and termination of pregnancies (TOPs) before and after CIN treatment using nationwide registers. Women were followed up until death, emigration, sterilization, or the end of 2004. The comparison of incidence of pregnancy outcomes before and after the treatment was estimated by calculating hazard ratios (HRs) with conditional Poisson regression. After 76,162 woman-years of follow-up, the incidence of any pregnancy remained constant over CIN-treatment, HR 1.02 and 95% confidence interval (CI) 0.97-1.08, but the incidence of the first pregnancy was significantly elevated after treatment, HR 1.13, and 95% CI 1.03-1.23. The incidence of live births was significantly elevated after treatment, HR 1.08 and 95% CI 1.01-1.15. Incidence of miscarriages, TOPs, extrauterine pregnancies, and molar pregnancies was not elevated. TOPs was significantly increased in the first pregnancy, HR 1.40, 95% CI 1.15-1.72 and after treatment by the loop electrosurgical excision procedure (LEEP), HR 1.36, 95% CI 1.15-1.60. CIN treatment did not reduce pregnancy incidence and women had more live births after than before CIN treatment. TOPs was more common in the first pregnancy or after treatment by LEEP. We encourage research on the psychosocial consequences of CIN treatment also in other countries and settings.

Body mass index and cancer incidence: the FINRISK study.

The relation between body mass index (BMI) and risk of cancer incidence is controversial. Cancer incidence during 1972-2008 in relation to BMI was investigated in a prospective cohort of 54,725 Finns aged 24-74 years and free of cancer at enrollment. Over a mean follow-up of 20.6 years, 8,429 (15.4%) incident cancers were recorded, 4,208 (49.9%) from men. Both parametric and nonparametric approaches were used to evaluate the shape of the relationship between BMI and incidence of cancer. BMI had a linear positive association with incidence of cancers of the colon, liver, kidney, bladder and all sites combined in men, and of cancers of the stomach, colon, gallbladder and ovary in women, an inverse association with incidence of cancers of the lung in men and the lung and breast in women, a J-shaped association with incidence of all cancers combined in women. High BMI in women was associated with an increased overall cancer risk in never smokers but a reduced risk in smokers. Elevated BMI was associated with an increased risk of incidence of cancers of certain sites.

Breast carcinoma detection modes and death in a female population in relation to population-based mammography screening.

PURPOSE: Associations between population-based screening, breast carcinoma detection modes and breast carcinoma death have not been studied using nationwide data at individual level. We evaluated these in Finland, where invitational age is gradually expanding from 50-59 to 50-69 years in 2008-2017. We also predicted breast carcinoma patterns in 2020 to assess the impact of changing invitational policy on breast carcinoma incidence and mortality. METHODS: The data included breast carcinomas in 2000-2010 (n = 48 040), and deaths due to these carcinomas (n = 4722). We divided carcinomas into those detected before or after the screening age, and those detected at the screening age. The latter was further divided into screen-detected and interval carcinomas, and carcinomas in the non-attendees. The prediction of future patterns was based on incidence data from the ten-year period 1998-2007 preceding the period of expanding invitational age in the national programme. RESULTS: Approximately 13% of in situ carcinomas were detected before, 29% after, and 57% at the screening age. In invasive cancers, the percentages were 16%, 42%, and 42%, respectively. At the screening age, more than half of invasive cancers were screening-detected, one quarter interval cancers, and one out of six cancers in the non-attendees. Almost 60% of breast cancer deaths were due to cancers detected after the screening age. By 2020, breast cancers detected at the screening age will increase from 42% to 65%, and breast cancers detected by screening from 23% to 38%. CONCLUSIONS: The study demonstrates a novel approach to examine associations between breast carcinoma incidence and mortality within and outside population-based screening. The results show mammography screening having a distinct role in overall breast carcinoma incidence and mortality.

Lifetime physical activity and cancer incidence--a cohort study of male former elite athletes in Finland.

OBJECTIVES: Physical activity has been shown to decrease the risk of certain cancers. Objective of this study was to assess the effect of physical activity on cancer incidence in former male athletes in older age. DESIGN: A cohort of 2448 elite male athletes and 1712 referents was followed-up for cancer incidence during 1986-2010 through the Finnish Cancer Registry. METHODS: Standardised incidence ratios were calculated with the general male population as the reference. Self-reported questionnaire-based data on covariates were used in Cox regression analyses comparing the risk of cancer in athletes and referents. RESULTS: The overall cancer incidence was lower in athletes than in the general population, standardised incidence ratio 0.89 (95% confidence interval 0.81-0.97). It was lowest among middle-distance runners (standardised incidence ratio 0.51, 95% confidence interval 0.22-1.01), long-distance runners (standardised incidence ratio 0.57, 95% confidence interval 0.35-0.88) and jumpers (standardised incidence ratio 0.60, 95% confidence interval 0.37-0.92). The standardised incidence ratio of lung cancer among athletes was 0.40 (95% confidence interval 0.27-0.55) and that of kidney cancer 0.23 (95% confidence interval 0.06-0.57). The hazard ratio for lung cancer between athletes and referents increased from the unadjusted ratio of 0.29 (95% confidence interval: 0.18-0.48) to 0.61 (95% confidence interval: 0.30-1.26) after adjustment for smoking status and pack-years of smoking. CONCLUSIONS: Former male elite athletes evidently have less cancer than men on the average. The lesser risk can be attributed to lifestyle factors, notably less frequent smoking among the athletes.

Effect of various forms of postmenopausal hormone therapy on the risk of ovarian cancer--a population-based case control study from Finland.

Postmenopausal hormone therapy (HT) associates with an increased risk of ovarian cancer, but its' influence on tumor histology is not as well known. Therefore, we evaluated the effect of various types of HT on the risk of epithelial ovarian cancer by histological subtype. All Finnish women diagnosed with ovarian cancer (n = 3,958) aged over 50 during 1995-2007 were identified from the Finnish Cancer Registry. For each case, three controls, matched for age and place of residence, were recruited from the Finnish National Population Register, which also provided data on parity and ages at deliveries. After exclusion of controls with oophorectomy, 11,325 controls remained. The prescription register provided HT use from age 50. Odds ratios (OR) for different HTs were estimated by conditional logistic regression: adjusted for parity, ages at deliveries and hysterectomy. Estradiol-only therapy use for 5 years or more associated with an increased risk (OR 1.45; 95% confidence interval 1.20-1.75) of a serous subtype, but with a decreased risk of mucinous subtype (0.35; 0.19-0.67). Use of sequential estradiol-progestin therapy (EPT) for 5 years or more associated with an increase in overall ovarian cancer risk (1.35; 1.20-1.63) and with an increase in the endometrioid subtype (1.88; 1.24-2.86) particularly. Continuous EPT, estradiol + levonorgestrel-releasing intrauterine system or tibolone had no effect on overall ovarian cancer risk. In conclusion, only sequential EPT use for 5 years or more associates with an increased risk of overall ovarian cancer. Furthermore, HT regimens differ significantly in their association with various histological types of ovarian cancer.

Stillbirth, early death and neonatal morbidity among offspring of female cancer survivors.

BACKGROUND: Increased awareness of the adverse effects of cancer treatments has prompted the development of fertility preserving regimens for the growing population of cancer survivors who desire to have children of their own. MATERIAL AND METHODS: We conducted a registry-based study to evaluate the risk of stillbirth, early death and neonatal morbidity among children of female cancer survivors (0-34 years at diagnosis) compared with children of female siblings. A total of 3501 and 16 908 children of female cancer patients and siblings, respectively, were linked to the national medical birth and cause-of-death registers. RESULTS: The risk of stillbirth or early death was not significantly increased among offspring of cancer survivors as compared to offspring of siblings: the risk [Odds Ratio (OR)] of early neonatal death, i.e. mortality within the first week was 1.35, with a 95% confidence interval (CI) of 0.58-3.18, within 28 days 1.40, 95% CI 0.46-4.24 and within the first year of life 1.11, 95% CI 0.64-1.93 after adjustment for the main explanatory variables. All these risk estimates were reduced towards one after further adjustment for duration of pregnancy. Measures of serious neonatal morbidity were not significantly increased among the children of survivors. However, there was a significant increase in the monitoring of children of cancer survivors for neonatal conditions (OR 1.56, 95% CI 1.35-1.80), which persisted even after correcting for duration of pregnancy, that might be related to parental cancer and its treatment or increased surveillance among the children. CONCLUSION: Offspring of cancer survivors were more likely to require monitoring or care in a neonatal intensive care unit, but the risk of early death or stillbirth was not increased after adjustment for prematurity. Due to the rarity of the mortality outcomes studied, collaborative studies may be helpful in ruling out the possibility of an increased risk among offspring of cancer survivors.

Endometrial cancer associated with various forms of postmenopausal hormone therapy: a case control study.

This study evaluates the effect of different modes of estradiol-progestagen therapy (EPT) regimens on the postmenopausal endometrial cancer risk in Finland. Women diagnosed with endometrial cancer in 1995-2007 at the age of 50-80 years were identified from the Finnish Cancer Registry (N = 7,261). For each case, three age-matched controls were retrieved from the Finnish Population Register. The use of EPT since 1994 was ascertained from the national Medical Reimbursement Register. Odds ratios (ORs) for different EPT regimens were calculated with conditional logistic regression analysis, adjusted for parity and ages at the deliveries. For use of <5 years, the OR for sequential EPT was 0.67 (95% confidence interval 0.52-0.86), for continuous EPT 0.45 (0.27-0.73), and for estradiol plus levonorgestrel-releasing intrauterine device system (LNG-IUS) 0.39 (0.17-0.88). A decreased risk persisted for the use of continuous EPT and estradiol plus LNG-IUS of up to 10 years. The use of long-cycle EPT showed a tendency toward an elevated risk both for exposure of <5 years (1.40; 0.82-2.38) and for estimated use of >5 years (1.63; 1.12-2.38). For an estimated exposure of >10 years, the risk for endometrial cancer was elevated for both users of long-cycle EPT (2.95; 2.40-3.62) and sequential EPT (1.38; 1.15-1.66). Norethisterone acetate and medroxyprogesterone acetate as parts of EPT did not differ in their endometrial cancer risk. The use of tibolone showed no endometrial risk. The use of sequential and long-cycle EPT is associated with an increased risk of endometrial cancer, whereas the use of continuous EPT or estradiol plus LNG-IUS shows a decreased risk.