Estimating the prevalence of breast cancer using a disease model: data problems and trends

BACKGROUND: Health policy and planning depend on quantitative data of disease epidemiology. However, empirical data are often incomplete or are of questionable validity. Disease models describing the relationship between incidence, prevalence and mortality are used to detect data problems or supplement missing data. Because time trends in the data affect their outcome, we compared the extent to which trends and known data problems affected model outcome for breast cancer. METHODS: We calculated breast cancer prevalence from Dutch incidence and mortality data (the Netherlands Cancer Registry and Statistics Netherlands) and compared this to regionally available prevalence data (Eindhoven Cancer Registry, IKZ). Subsequently, we recalculated the model adjusting for 1) limitations of the prevalence data, 2) a trend in incidence, 3) secondary primaries, and 4) excess mortality due to non-breast cancer deaths. RESULTS: There was a large discrepancy between calculated and IKZ prevalence, which could be explained for 60% by the limitations of the prevalence data plus the trend in incidence. Secondary primaries and excess mortality had relatively small effects only (explaining 17% and 6%, respectively), leaving a smaller part of the difference unexplained. CONCLUSION: IPM models can be useful both for checking data inconsistencies and for supplementing incomplete data, but their results should be interpreted with caution. Unknown data problems and trends may affect the outcome and in the absence of additional data, expert opinion is the only available judge

What can we learn from geographical comparisons of childhood cancer survival?

With improvements in treatment for childhood cancer, comparisons of survival rates between countries have become important to inform future health policies and treatment strategies. Population-based cancer registry data are viewed as the gold standard for such comparisons, but even these have potential confounding factors. Here, we review the interpretation of recent geographical comparisons of childhood cancer survival from the viewpoint of the British Isles, a region with a 45-year record of national population-based cancer registration and a national childhood cancer clinical trials organisation in place for nearly 30 years. Using national data on referral patterns to tertiary paediatric oncology centres, we explore some of the reasons for lower survival rates in the past for some tumour groups and anticipate continued improvement in the next decade. Participation in international clinical trials coincided with rapid gains in survival for hepatoblastoma. This exemplifies the potential benefits of international collaborative clinical research, particularly for rare subgroups

Prognostic value of morphology and hormone receptor status in breast cancer - a population based study

We analysed the 5-year relative survival among 4473 breast cancer cases diagnosed in 1990-1992 from cancer registries in Estonia, France, Italy, Spain, the Netherlands and the UK. Among eight categories based on ICD-O codes (infiltrating ductal carcinoma, lobular plus mixed carcinoma, comedocarcinoma, 'special types', medullary carcinoma, not otherwise specified (NOS) carcinoma, other carcinoma and cancer without microscopic confirmation), the 5-year relative survival ranged from 66% (95% CI 61-71) for NOS carcinoma to 95% (95% CI 90-100) for special types (tubular, apocrine, cribriform, papillary, mucinous and signet ring cell); 27% (95% CI 18-36) for cases without microscopic confirmation. Differences in 5-year relative survival by tumor morphology and hormone receptor status were modelled using a multiple regression approach based on generalised linear models. Morphology and hormone receptor status were confirmed as significant survival predictors in this population-based study, even after adjusting for age and stage at diagnosis

Debating the Desirability of New Biomedical Technologies: Lessons from the Introduction of Breast Cancer Screening in the Netherlands

Health technology assessment (HTA) was developed in the 1970s and 1980s to facilitate decision making on the desirability of new biomedical technologies. Since then, many of the standard tools and methods of HTA have been criticized for their implicit normativity. At the same time research into the character of technology in practice has motivated philosophers, sociologists and anthropologists to criticize the traditional view of technology as a neutral instrument designed to perform a specific function. Such research suggests that the tools and methods of more traditional forms of HTA are often inspired by an ‘instrumentalist’ conception of technology that does not fit the way technology actually works. This paper explores this hypothesis for a specific case: the assessments and deliberations leading to the introduction of breast cancer screening in the Netherlands. After reconstructing this history of HTA ‘in the making’ the stepwise model of HTA that emerged during the process is discussed. This model was rooted indeed in an instrumentalist conception of technology. However, a more detailed reconstruction of several episodes from this history reveals how the actors already experienced the inadequacy of some of the instrumentalist presuppositions. The historical case thus shows how an instrumentalist conception of technology may result in implicit normative effects. The paper concludes that an instrumentalist view of technology is not a good starting point for HTA and briefly suggests how the fit between HTA methods and the actual character of technology in practice might be improved

Safety of aromatase inhibitors in the adjuvant setting

The third-generation aromatase inhibitors (AIs) letrozole, anastrozole, and exemestane are replacing tamoxifen as adjuvant therapy in most postmenopausal women with early breast cancer. Although AIs have demonstrated superior efficacy and better overall safety compared with tamoxifen in randomized controlled trials, they may not provide the cardioprotective effects of tamoxifen, and bone loss may be a concern with their long-term adjuvant use. Patients require regular bone mineral density monitoring, and prophylactic bisphosphonates are being evaluated to determine whether they may protect long-term bone health. AIs decrease the risks of thromboembolic and cerebrovascular events compared with tamoxifen, and the overall rate of cardiovascular events in patients treated with AIs is within the range seen in age-matched, non-breast-cancer populations. AIs are also associated with a lower incidence of endometrial cancer and fewer vaginal bleeding/discharge events than tamoxifen. Compared with tamoxifen, the incidence of hot flashes is lower with anastrozole and letrozole but may be higher with exemestane. Generally, adverse events with AIs are predictable and manageable, whereas tamoxifen may be associated with life-threatening events in a minority of patients. Overall, the benefits of AIs over tamoxifen are achieved without compromising overall quality of life

Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered

Variation in survival of European children with acute lymphoblastic leukaemia, diagnosed in 1978-1992: the EUROCARE study

The aim of this study was to provide a comparative description of geographical variations and time trends in the population-based survival of European children with acute lymphoblastic leukaemia (ALL). Data on 13 344 newly diagnosed children (0-14 years) with ALL were included in the EUROCARE study and were collected were collected by 34 population-based cancer registries (four comprising only childhood malignancies), operating in 17 countries (four in Scandinavia, two in Southern Europe, three in Eastern Europe, six in Continental Europe and two in the UK). Age-specific crude survival rates were estimated for boys and girls according to country for the period 1985-1989 and in adjusted form to attain comparability. Overall pooled and weighted rates were estimated as European standards. Children dead at diagnosis or diagnosed only through a death certificate were excluded. Geographical variation was also estimated by calculating the relative death rate with respect to the pooled overall European rate. After adjustment for age, gender and country, a Cox regression analysis was used to estimate time trends in survival. Survival was compared with that in the USA, Japan, Canada and Australia. During 1985-1989, the 1-year survival rate varied from 99 to 79%, the 5-year survival rate from over 80 to 56% (with the exception of Estonia; 34%; 95% confidence interval (CI) 20-52) among the various countries; the European weighted means were 90 (95% CI 87-93) and 72% (95% CI 69-75), respectively. Survival was particularly favourable in (south) Sweden, Finland, Germany and The Netherlands and rather unfavourable in Estonia and (surprisingly) France, where only 4% of its population was covered by the participating registries. Compared with the period 1978-1981, the hazard ratio for the period 1986-1989 decreased to 0.59 (95% CI 0.54-0.64) and - in a smaller set of registries - to 0.49 (0.45-0.55) for 1990-1992, an annual decrease in this rate of approximately 3.5%. During 1985-1989, the 5-year survival rates for European children were largely similar to those found in the USA, Canada and Australia, but markedly better than those in Japan. Higher survival rates were found for countries with 'good' access to centrally organised diagnostic and treatment facilities which stimulated 'agggressive' treatments according to a protocol. However, a subdivision according to risk profiles, e.g. according to the initial white blood cell count at diagnosis, could not be made and this might have explained partially the geographical differences in survival, because a positive association appeared between incidence at age 1-4 years and 5-year survival in most countries. (C) 2001 Elsevier Science Ltd. All rights reserved