Impact of subtypes and comorbidities on breast cancer relapse and survival in population-based studies.

OBJECTIVE: To study the impact of subtypes and comorbidities on breast cancer (BC) relapse and survival in the heterogeneous patients of the real world. METHODS: We identified patients diagnosed with BC between January 2003 and December 2005 from six population-based Swiss cancer registries. Clinicopathologic data was completed with information on locoregional and distant relapse and date and cause of death for over 10-years. We approximated BC subtypes using grade and the immunohistochemical panel for oestrogen, progesterone and human epidermal growth factor 2 (HER2) receptor status. We studied factors affecting relapse and survival. RESULTS: Luminal A-like subtype represented 46% of all newly diagnosed BC (N = 1831), followed by luminal B-like (N = 1504, 38%), triple negative (N = 436, 11%) and HER2 enriched (N = 204, 5%). We observed regional disparities in subtype prevalence that contribute to explain regional differences in survival formerly described. Disease relapse and BC specific mortality differed by subtype and were lower for luminal A like tumours than for other subtypes for any stage at diagnosis. After a median follow-up of 10.9 years, 1311 (33%) had died, half of them 647 (16%) due to another disease, showing the importance of comorbidities. Omission of systemic therapies in selected patients was not associated with poorer BC specific survival, BC subtype and life expectancy playing a role. CONCLUSIONS: Information on tumour subtype is necessary for an adequate interpretation of population-based BC studies. Measures of comorbidity or frailty help in the evaluation of quality of care in the highly heterogeneous patients of the real world.

Multiple primary tumours: challenges and approaches, a review.

When in a patient more than one tumour in the same or a different organ is diagnosed, multiple primary tumours may be present. For epidemiological studies, different definitions of multiple primaries are used with the two main definitions coming from the project Surveillance Epidemiology and End Results and the International Association of Cancer Registries and International Agency for Research on Cancer. The differences in the two definitions have to be taken into consideration when reports on multiple primaries are analysed. In this review, the literature on multiple primaries is reviewed and summarised. Overall, the frequency of multiple primaries is reported in the range of 2-17%. Aetiological factors that may predispose patients to multiple primaries can be grouped into host related, lifestyle factors and environmental influences. Some of the most common cancer predisposition syndromes based on a clinical presentation are discussed and the relevant genetic evaluation and testing are characterised. Importantly, from a clinical standpoint, clinical situations when multiple primaries should be suspected and ruled out in a patient are discussed. Furthermore, general principles and possible treatment strategies for patients with synchronous and metachronous multiple primary tumours are highlighted.

Evaluation of completeness of case ascertainment in Swiss cancer registration.

This is the first comprehensive evaluation of completeness of case ascertainment in Swiss cancer registration. There is currently no method available that is considered to be the gold standard. Apart from simple measures such as the proportion of cases where registration was initiated by a death certificate and the proportion of diagnoses on the basis of histology or cytology/haematology, we applied two dedicated approaches: (i) the semiquantitative method of comparing the mortality to incidence rate ratio with relative survival (MI-Surv method) and (ii) the Flow method, which provides a quantitative estimate for the completeness depending on time since diagnosis. All 10 Swiss cancer registries in operation since at least 2006 and providing the required parameters were included. Simple and dedicated methods showed high completeness across all cancer registries and for most cancer types tested, with the notable exception of lymphoid leukaemia.

Trends in incidence of oesophageal and gastric cancer according to morphology and anatomical location, in Switzerland 1982-2011.

QUESTION UNDER STUDY/PRINCIPLES: This study aimed to evaluate trends in the incidence of oesophageal and gastric cancer by anatomical location and histology using nationally representative Swiss data. METHODS: We included all oesophageal and gastric cancers recorded in 10 Swiss population-based cancer registries 1982-2011. We calculated age-standardised incidence rates (ASIRs) per 100 000 person-years (PY) (European standard) for both cancer sites stratified by sex, language region (German, French-Italian), morphology and anatomical location. To assess time trends, we estimated annual percentage changes (APCs) with 95% confidence intervals (95% CIs). RESULTS: ASIR of oesophageal adenocarcinoma increased in both sexes and language regions (p <0.001). The steepest increase occurred in males of the German-speaking region (APC 6.8%, 95% CI 5.8-7.8) with ASIRs of 0.8 per 100,000 PY in 1982-1987 and 3.9 per 100.000 PY in 2007-2011. Incidence of oesophageal squamous cell carcinoma decreased significantly in males of both language regions by around -1.5% per year. In contrast, a slight but significant increase (APC 1.4%, 95% CI 0.3-2.4]) of oesophageal squamous cell carcinoma was observed in females of the German-speaking region. We observed stable rates for cancer of the gastric cardia. The incidence of noncardia gastric cancer decreased substantially in both sexes and language regions (p <0.001). CONCLUSION: In Switzerland, the incidence of oesophageal adenocarcinoma has risen whereas incidence of noncardia gastric cancer has decreased substantially as observed in other developed countries.

Cancer survivors in Switzerland: a rapidly growing population to care for.

BACKGROUND: Cancer survivors are a heterogeneous group with complex health problems. Data concerning its total number and growing dynamics for Switzerland are scarce and outdated. METHODS: Population and mortality data were retrieved from the Swiss Federal Statistical Office (FSO). Incidence and relative survival for invasive cancers were computed using data from the cancer registries Geneva (1970-2009), St. Gallen - Appenzell (1980-2010), Grisons & Glarus (1989-2010), and Valais (1989-2010). We estimated prevalence for 1990-2010 using the Prevalence, Incidence Approach MODel (PIAMOD) method. We calculated trends in prevalence estimates by Joinpoint analysis. Projections were extrapolated using the above models and based on time trends of the period 2007-2010. RESULTS: The estimated number of cancer survivors increased from 139'717 in 1990 (2.08% of the population) to 289'797 persons in 2010 (3.70%). The growth rate shows an exponential shape and was 3.3% per year in the period 2008 to 2010. Almost half of the survivors have a history of breast, prostate or colorectal cancer. Among cancer survivors, 55% are women but the increases have been more marked in men (p < 0.01, 3.9% annual increase in men vs. 2.7% in women since 2008). By the end of 2020 372'000 cancer survivors are expected to live in Switzerland. CONCLUSIONS: There is a rapidly growing population of cancer survivors in Switzerland whose needs and concerns are largely unknown.

Bayesian spatio-temporal modelling of tobacco-related cancer mortality in Switzerland.

Tobacco smoking is a main cause of disease in Switzerland; lung cancer being the most common cancer mortality in men and the second most common in women. Although disease-specific mortality is decreasing in men, it is steadily increasing in women. The four language regions in this country might play a role in this context as they are influenced in different ways by the cultural and social behaviour of neighbouring countries. Bayesian hierarchical spatio-temporal, negative binomial models were fitted on subgroup-specific death rates indirectly standardized by national references to explore age- and gender-specific spatio-temporal patterns of mortality due to lung cancer and other tobacco-related cancers in Switzerland for the time period 1969-2002. Differences influenced by linguistic region and life in rural or urban areas were also accounted for. Male lung cancer mortality was found to be rather homogeneous in space, whereas women were confirmed to be more affected in urban regions. Compared to the German-speaking part, female mortality was higher in the French-speaking part of the country, a result contradicting other reports of similar comparisons between France and Germany. The spatio-temporal patterns of mortality were similar for lung cancer and other tobacco-related cancers. The estimated mortality maps can support the planning in health care services and evaluation of a national tobacco control programme. Better understanding of spatial and temporal variation of cancer of the lung and other tobacco-related cancers may help in allocating resources for more effective screening, diagnosis and therapy. The methodology can be applied to similar studies in other settings.

Tobacco-related cancer mortality: projections for different geographical regions in Switzerland.

PRINCIPLES: Switzerland is divided into 26 cantons of variable population size and cultural characteristics. Although a federal law to protect against passive smoking and a national tobacco control programme exist, details of tobacco-related policies are canton-specific. This study aimed to project gender-specific tobacco-related cancer mortality in Switzerland at different geographical levels for the periods 2009-2013 and 2014-2018. METHODS: In this analysis, data on Swiss tobacco-related cancer mortality from 1984 until 2008 were used. Bayesian age-period-cohort models were formulated to assess past trends of gender-specific tobacco-related cancer mortality and to project them up to 2018 at cantonal and language region levels. Furthermore, estimates are provided on a national scale by age categories of 50-69 and ≥70 years. RESULTS: Model-based estimates at cantonal level identified regions with low and high tobacco-related cancer mortality rates for the observed and projected periods. Our analysis based on language regions showed the lowest mortality in the German-speaking part. Projections at national level, between younger (age 50-69) and older (age ≥70) males, indicated an ongoing decreasing trend for males but an upward trend for females. The gap in tobacco-related cancer mortality rates between younger and older males seems to be shrinking. In females, a stronger rise was obtained for the younger age group. CONCLUSION: Our findings indicate region-, sex- and age-related differences in tobacco-related cancer mortality in Switzerland and this could be useful for healthcare planning and for evaluating the impact of canton-specific tobacco-related policies and interventions.

How reliable is Ki-67 immunohistochemistry in grade 2 breast carcinomas? A QA study of the Swiss Working Group of Breast- and Gynecopathologists.

UNLABELLED: Adjuvant chemotherapy decisions in breast cancer are increasingly based on the pathologist's assessment of tumor proliferation. The Swiss Working Group of Gyneco- and Breast Pathologists has surveyed inter- and intraobserver consistency of Ki-67-based proliferative fraction in breast carcinomas. METHODS: Five pathologists evaluated MIB-1-labeling index (LI) in ten breast carcinomas (G1, G2, G3) by counting and eyeballing. In the same way, 15 pathologists all over Switzerland then assessed MIB-1-LI on three G2 carcinomas, in self-selected or pre-defined areas of the tumors, comparing centrally immunostained slides with slides immunostained in the different laboratoires. To study intra-observer variability, the same tumors were re-examined 4 months later. RESULTS: The Kappa values for the first series of ten carcinomas of various degrees of differentiation showed good to very good agreement for MIB-1-LI (Kappa 0.56-0.72). However, we found very high inter-observer variabilities (Kappa 0.04-0.14) in the read-outs of the G2 carcinomas. It was not possible to explain the inconsistencies exclusively by any of the following factors: (i) pathologists' divergent definitions of what counts as a positive nucleus (ii) the mode of assessment (counting vs. eyeballing), (iii) immunostaining technique, and (iv) the selection of the tumor area in which to count. Despite intensive confrontation of all participating pathologists with the problem, inter-observer agreement did not improve when the same slides were re-examined 4 months later (Kappa 0.01-0.04) and intra-observer agreement was likewise poor (Kappa 0.00-0.35). CONCLUSION: Assessment of mid-range Ki-67-LI suffers from high inter- and intra-observer variability. Oncologists should be aware of this caveat when using Ki-67-LI as a basis for treatment decisions in moderately differentiated breast carcinomas.

A population-based study on the patterns of use of different chemotherapy regimens in Swiss patients with early breast cancer.

BACKGROUND: There is considerable heterogeneity in the use of chemotherapy in early breast cancer (BC), despite international recommendations issued from the NCCN, NIH and the St.Gallen bi-annual conference. METHODS: We included 1,535 patients from seven Swiss cancer registries between 2003 and 2005 receiving chemotherapy for stage I to III BC. Chemotherapy was categorised into (a) FAC/FEC, anthracyclines followed by CMF or anthracycline-taxane combinations (FAC-T) (781 patients) and (b) other chemotherapy regimens such as CMF/AC (EC) (754 patients). Predictors for choosing FAC-T over non-FAC-T chemotherapy were separately determined in all patients and in ER-negative patients (n = 496) by multivariate logistic regression analysis. RESULTS: The use of FAC-T increased significantly over time, from 44% in 2003 to 55% in 2005. BC stage III (versus stage I-II) and nodal positivity were the predominant predictors for using FAC-T chemotherapy in the adjusted model (odds ratio (OR) 4.1, 95%-confidence intervals (CI) 2.6-6.3 and OR 3.0, 95%-CI 2.0-4.4, respectively). In high-risk ER-negative BC patients, poor histological differentiation was more important to choose FAC-T chemotherapy (OR 3.8, 95%-CI 1.9-7.5) than tumour stage or nodal status. The use of FAC-T chemotherapy varied substantially among the seven geographic regions, from 20% in rural Grisons-Glarus to 73% in Zurich. CONCLUSIONS: Tumour biology is a predominant factor for choosing FAC-T over older chemotherapy regimens in patients with ER-negative early BC, but improvements should be made to reduce the substantial regional heterogeneity. Further epidemiological studies should assess how the use of FAC-T chemotherapy is affecting clinical outcome in patients with early BC and different risk profiles.

A population-based study on the implementation of treatment recommendations for chemotherapy in early breast cancer.

BACKGROUND: There is considerable heterogeneity in the use of chemotherapy for patients with early breast cancer (BC), despite international recommendations issued from the National Comprehensive Cancer Network (NCCN), National Institutes of Health (NIH), and the St. Gallen biannual conference. This population-based study assessed the patterns of chemotherapy use in early BC. PATIENTS AND METHODS: The study included all or representative samples of patients with stage I-III BC from 7 Swiss cancer registries between 2003 and 2005. Factors modifying chemotherapy use were determined by logistic regression, considering patients receiving chemotherapy as cases (n = 1535) and the others as controls (n = 2004). RESULTS: Nodal involvement was by far the strongest predictor for the use of chemotherapy (adjusted odds ratio [OR], 9.7; 95% confidence interval [CI], 7.2-13.0). Tumor biological characteristics such as histologic differentiation (OR, 4.4; 95% CI, 3.2-6.2), estrogen receptor (ER) status (OR, 3.8; 95% CI, 2.6-5.5), human epidermal growth factor receptor 2 (HER2) status (OR, 1.9; 95% CI, 1.3-2.7), and patient age (OR, 4.6; 95% CI, 3.5-6.2) were less important predictors for chemotherapy use. Socioeconomic and provider-related factors, such as patient education, affluence, insurance, breast surgeon's annual caseload, and case presentation at a multidisciplinary tumor conference did not predict the use of chemotherapy, with the exception of the health care provider's participation in clinical research (OR, 2.1; 95% CI, 1.6-2.8). The patient's region of residence did not predict the use of chemotherapy, but it was associated with the specific type of chemotherapy used. CONCLUSION: Nodal status, rather than surrogate markers for tumor biological features, was the predominant factor for choosing chemotherapy in patients with early BC in this large population study. Improvements should be made to increase the weight of tumor biological features in choosing chemotherapy in early BC.

A ciliated cyst in the posterior mediastinum compatible with a paravertebral Mullerian cyst.

Several types of cysts in the mediastinum have been described, such as bronchogenic or thymic cysts and esophageal duplications, most of which arise in the middle or posterior mediastinum close to the tracheobronchial system or the esophagus. We present herein the rare case of a ciliated cyst anatomically distant to the genitourinary organs. An abnormal formation in the posterior mediastinum was incidentally detected on chest X-ray during the preoperative evaluation for a herniorrhaphy in a 54-year-old woman who had a negative medical history. The patient exhibited no clinical signs or symptoms associated with the mass. MRI revealed hypointense signals in T1-weighted scans and homogeneous hyperintense signals in T2-weighted scans. The lesion was resected thoracoscopically and histologic and immunohistochemical stainings showed a ciliated cyst of probable Mullerian origin. Because of their uncertain biological behavior, cystic lesions in the posterior mediastinum should be removed surgically to allow definitive histologic diagnosis.