Danish-German cross-border analysis of breast cancer survival.
Cancer registry data were analysed using Kaplan-Meier curves and Cox regression.
Lower survival was observed in the Danish regions compared to the German region.
Survival differences diminished after adjustment for time, stage and treatment.
The gap closes due to Denmark’s screening programme and increased adjuvant therapy.
Background and Aim
Denmark reports slightly lower breast cancer survival before 2010 than its neighbouring country Germany. Previous research is limited by lacking stage and treatment information. This study aims to investigate differences in breast cancer survival between the bordering regions Schleswig-Holstein (Germany), Southern Denmark and Zealand (Denmark) using registry data including stage and treatment information.
Invasive female breast cancer cases diagnosed during 2004−2013 with follow up through 31st December 2014 were extracted from cancer registries. Cases notified by death certificates only and those aged 90+ years were excluded. Kaplan-Meier curves and log-rank tests were computed. Cox regression analysis was conducted with adjustment for year of diagnosis, age, stage, and treatment.
The analytical sample included 42,966 cases. Kaplan-Meier curves and log-rank tests show significant survival differences between the regions. The Cox regression model adjusted for year of diagnosis and age shows significantly worse overall survival of breast cancer patients in both Danish regions compared to Schleswig-Holstein with hazard ratios (HR) of 1.09 (95 % CI: 1.04; 1.15) for patients from Southern Denmark (SD) and 1.25 (95 % CI: 1.18; 1.32) for residents of Zealand (ZL). This effect diminished after adjustment for stage and treatment (HR: 1.05 (SD), 1.09 (ZL) 95 % CI: 0.99; 1.10 (SD), 1.03; 1.15 (ZL)).
Survival differences can be explained by differing stage distribution and treatment administration, which formerly were more favourable in Schleswig-Holstein. The survival gap will probably close due to Denmark’s national screening program and increased use of adjuvant cancer therapy.
Globally, breast cancer is the most common malignant neoplasm and the leading cause of cancer death in women [ ]. In Europe, recent trends show increasing incidence rates with simultaneously decreasing mortality rates [ ] and improvements in survival among female breast cancer patients [ ]. Denmark was and is known to have lower overall and breast cancer-specific survival than other Nordic countries [ , ] and its neighbouring country Germany [ , ], though remarkable improvements have been observed on a national level in recent years [ ].
In past decades, significant efforts were made to compare cancer survival and explain survival differences across nations with constantly evolving studies such as EUROCARE [ ] and CONCORD [ ], but these also came with limitations. The major limitation of previously published research based on the most recent EUROCARE-5-data, including amongst others Danish and German cancer registry data, is the lack of information about stage and treatment as the key prognostic factors for cancer survival [ , ]. Within EUROCARE and CONCORD protocols, high-resolution studies were conducted and clinical data on stage and treatment were collected successfully from many countries including Denmark, but German cancer registry data were not included [ , ]. However, a study by Storm et al. showed that meaningful survival comparisons of cancer registry data from Germany and Denmark are possible if additional variables like stage and treatment are taken into account as exemplified by cancer registry data for colorectal cancers [ ]. Taking stage and treatment into account is important, as Germany’s and Denmark’s universal health care systems differ substantially, e.g. in terms of accessibility to specialized care (gatekeeper function of Danish general practitioners (GPs) versus free choice of physicians in Germany), implementation of early detection programs, treatment capacities and funding [ ].
Cross-border collaboration in cancer research and care between the German federal state Schleswig-Holstein and the bordering Danish regions Southern Denmark and Zealand was established in 2007 [ ] and expanded since. In light of this program, our aim was to investigate regional differences in breast cancer survival using cancer registry data, including clinical information, to assess i) whether regional survival differences exist and ii) the extent to which they can be explained by tumour stage at diagnosis and type of treatment.