Predicting second breast cancer among women with primary breast cancer using machine learning algorithms, a population-based observational study.

Breast cancer survivors often experience recurrence or a second primary cancer. We developed an automated approach to predict the occurrence of any second breast cancer (SBC) using patient-level data and explored the generalizability of the models with an external validation data source. Breast cancer patients from the cancer registry of Zurich, Zug, Schaffhausen, Schwyz (N = 3213; training dataset) and the cancer registry of Ticino (N = 1073; external validation dataset), diagnosed between 2010 and 2018, were used for model training and validation, respectively. Machine learning (ML) methods, namely a feed-forward neural network (ANN), logistic regression, and extreme gradient boosting (XGB) were employed for classification. The best-performing model was selected based on the receiver operating characteristic (ROC) curve. Key characteristics contributing to a high SBC risk were identified. SBC was diagnosed in 6% of all cases. The most important features for SBC prediction were age at incidence, year of birth, stage, and extent of the pathological primary tumor. The ANN model had the highest area under the ROC curve with 0.78 (95% confidence interval [CI] 0.750.82) in the training data and 0.70 (95% CI 0.61-0.79) in the external validation data. Investigating the generalizability of different ML algorithms, we found that the ANN generalized better than the other models on the external validation data. This research is a first step towards the development of an automated tool that could assist clinicians in the identification of women at high risk of developing an SBC and potentially preventing it.

Geographical variation in malignant and benign/borderline brain and CNS tumor incidence: a comparison between a high-income and a middle-income country.

PURPOSE: There is large variability in reported incidence rates of primary brain/CNS tumors across the world, with mostly higher rates in higher-income countries. The aim was to compare malignant and benign brain/CNS tumor incidence between Zurich (Switzerland), a high-income country, and Georgia, a lower middle-income country. METHODS: For the period March 2009 to February 2012, we extracted the following tumors based on topography according to ICD-O3: C70.0-C72.9, and C75.1 (pituitary gland). Data were categorized into histology groups based on the WHO 2007 histological classification. Age-standardized rates per 100,000 person-years were calculated by subgroups. RESULTS: We included 1104 and 1476 cases of primary brain/CNS tumors for Zurich and Georgia, respectively. Mean age of patients was significantly lower in Georgia compared to Zurich (50.0 versus 58.3 years). Overall age-standardized incidence rates for malignant and benign brain/CNS tumors were 10.5 (95% CI 9.9-11.0) for Georgia and 23.3 (95% CI 21.9-24.7) for Zurich with a ratio of benign to malignant tumors of 1.656 for Georgia and 1.946 for Zurich. The most frequent histology types were meningiomas in both regions, followed by glioblastomas in Zurich, but pituitary tumors in Georgia. CONCLUSION: Age-adjusted incidence rates of brain/CNS tumors were considerably higher in Zurich compared to Georgia, both for benign and malignant tumors, which is in line with other studies reporting higher rates in high-income than in low- and middle-income countries. The frequency distribution may be related to differences in diagnosing techniques and the population age structure.

Trends in prostate cancer incidence between 1996 and 2013 in two Swiss regions by age, grade, and T-stage.

PURPOSE: To investigate differences in prostate cancer incidence between two distinct Swiss regions from 1996 to 2013 stratified by age group, grade, and T-stage. METHODS: The dataset included 17,495 men living in Zurich and 3,505 men living in Ticino, diagnosed with prostate cancer between 1996 and 2013. We computed age-standardized incidence rates per 100,000 person-years using the European Standard Population. Trends were assessed using JoinPoint regression analysis Software. RESULTS: Age-standardized incidence rates were generally higher in Zurich compared to Ticino but the difference decreased over time. Incidence rates increased significantly up to 2002 in Zurich and 2007 in Ticino and then decreased. A statistically significant increase was observed for men aged < 65 years, for grade 3 tumors, and for T-stage 2 and 3 tumors. The largest decrease was seen for grade 1 tumors. Furthermore, the incidence of tumors of unknown grade or T-stage decreased significantly in both regions. CONCLUSIONS: The trends in prostate cancer incidence rates were similar in both regions, although on a higher level in Zurich compared to Ticino. However, the difference decreased over time. The distribution of T-stage and grade did not explain the difference in incidence rates. Different use of opportunistic screening may play a role.

Glioblastoma in the Canton of Zurich, Switzerland revisited: 2005 to 2009.

BACKGROUND: A population-based analysis of patients with glioma diagnosed between 1980 and 1994 in the Canton of Zurich in Switzerland confirmed the overall poor prognosis of glioblastoma. To explore changes in outcome, registry data were reevaluated for patients diagnosed between 2005 and 2009. METHODS: Patients with glioblastoma who were diagnosed between 2005 and 2009 were identified by the Zurich and Zug Cancer Registry. The prognostic significance of epidemiological and clinical data, isocitrate dehydrogenase 1 (IDH1)(R132H) mutation status, and O6 methylguanine DNA methyltransferase (MGMT) promoter methylation status was analyzed using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: A total of 264 patients with glioblastoma were identified, for an annual incidence of 3.9 compared with the previous incidence of 3.7. The mean age of the patients at the time of diagnosis was 59.5 years in the current cohort compared with 61.3 years previously. The overall survival (OS) rate was 46.4% at 1 year, 22.5% at 2 years, and 14.4% at 3 years in the current study compared with 17.7% at 1 year, 3.3% at 2 years, and 1.2% at 3 years as reported previously. The median OS for all patients with glioblastoma was 11.5 months compared with 4.9 months in the former patient population. The median OS was 1.9 months for best supportive care, 6.2 months for radiotherapy alone, 6.7 months for temozolomide alone, and 17.0 months for radiotherapy plus temozolomide. Multivariate analysis revealed age, Karnofsky performance score, extent of tumor resection, first-line treatment, year of diagnosis, and MGMT promoter methylation status were associated with survival in patients with IDH1(R132H) -nonmutant glioblastoma. CONCLUSIONS: The OS of patients newly diagnosed with glioblastoma in the Canton of Zurich in Switzerland markedly improved from 1980 through 1994 to 2005 through 2009. Cancer 2016;122:2206-15. © 2016 American Cancer Society.

Preferences for the organization of long-term follow-up in adolescent and young adult cancer survivors.

PURPOSE: As survival rates of adolescent and young adult (AYA) cancer patients increase, a growing number of AYA cancer survivors need follow-up care. However, there is little research on their preferences for follow-up care. We aimed to (1) describe AYA cancer survivors' preferences for the organization and content of follow-up care, (2) describe their preferences for different models of follow-up, and (3) investigate clinical and sociodemographic characteristics associated with preferences for the different models. METHODS: AYA cancer survivors (diagnosed with cancer at age 16-25 years; ≥5 years after diagnosis) were identified through the Cancer Registry Zurich and Zug. Survivors completed a questionnaire on follow-up attendance, preferences for organizational aspects of follow-up care (what is important during follow-up, what should be included during appointments, what specialists should be involved, location), models of follow-up (telephone/questionnaire, general practitioner (GP), pediatric oncologist, medical oncologist, multidisciplinary team), and sociodemographic characteristics. Information on tumor and treatment was available through the Cancer Registry Zurich and Zug. RESULTS: Of 389 contacted survivors, 160 (41.1 %) participated and 92 (57.5 %) reported still attending follow-up. Medical aspects of follow-up care were more important than general aspects (p < 0.001). Among different organizational models, follow-up by a medical oncologist was rated higher than all other models (p = 0.002). Non-attenders of follow-up rated GP-led follow-up significantly higher than attenders (p = 0.001). CONCLUSION: Swiss AYA cancer survivors valued medical content of follow-up and showed a preference for medical oncologist-led follow-up. Implementation of different models of follow-up care might improve accessibility and attendance among AYA cancer survivors.

Differential expression of epithelial­mesenchymal transition and stem cell markers in intrinsic subtypes of breast cancer.

The transcription factors SLUG and SOX9 have been shown to define mammary stem cell state. Similarly, epithelial­mesenchymal transition (EMT) markers (E-Cadherin, mTOR) have been shown to play a role in tumor-progression and metastatic potential in breast cancer. Finally, SOX10 is known to be expressed in breast cancer as well. The overexpressions of EMT and stem cell markers have been shown to correlate with poor overall survival. In this study, we examined whether the expression of these markers correlates with intrinsic subtypes of breast cancer and whether there is a prognostic difference in their expression-profile. We analyzed 617 breast cancer samples from two tissue micro arrays. Breast cancer samples were categorized into three groups according to hormone receptor expression and HER2-status as Luminal A/B, HER2-positive, and triple negative subgroup. Immunohistochemical expressions of SLUG, SOX9, SOX10, E-Cadherin, and mTOR were semi-quantitatively analyzed using a two-tiered and three-tiered scoring system in which cytoplasmic and nuclear stains were considered. Strong nuclear expression of SLUG was observed preferentially in triple negative but not in Luminal A/B or HER2-positive cases (24 vs. 3 and 0 %, p < 0.001). Loss of SOX9 in the nuclear stain was less frequent in triple negative than in Luminal A/B or HER2-positive cases (4 vs. 9 vs. 13 %, p < 0.001). Expression of nuclear SOX10 was lower in triple negative than in Luminal A/B and HER2-positive cases (67 vs.78 and 79 %, p = 0.012). E-Cadherin loss was observed only in Luminal A/B tumors (p = 0.016), no difference in the mTOR expression was seen between any of the three groups. No correlation to conventional histopathological-parameters or stage could be established in our cohort. Our study shows an inversed preferential nuclear expression of SLUG, SOX10, and SOX9 in triple negative and non-triple negative cases. This information is important in understanding the biology of triple negative breast cancer, also in terms of future studies dealing with targeted therapies based on the alterations of EMT and stem cell markers.

Net survival of women diagnosed with breast tumours: a population-based study in Switzerland.

AIMS OF THE STUDY: Although the incidence of breast carcinoma in situ has been increasing, the prognosis of breast carcinoma in situ patients has not been extensively investigated. Thus, we aimed to compare the characteristics of invasive breast tumours based on whether or not they were preceded by a breast carcinoma in situ and to estimate the 5-year net survival of patients diagnosed with different breast tumours. METHODS: Data from women diagnosed with breast tumours between 2003 and 2016 were used in our analyses. Net survival analyses were performed using inverse probability of censoring weights (nonparametric Pohar Perme estimator). Under certain assumptions, differences in survival between the cancer population and the general population can be considered to be attributable to the cancer diagnosis (NS). RESULTS: Descriptive observation of tumour characteristics indicated that invasive breast tumours following a breast carcinoma in situ were more frequently detected at an earlier stage and had less missing information in tumour-specific variables, compared to invasive breast tumours not preceded by a breast carcinoma in situ. Breast carcinoma in situ patients had a 5-year net survival of 1.02 (95% CI: 1.01-1.03), whereas patients diagnosed with invasive breast cancer without a recorded breast carcinoma in situ had a 5-year net survival of 0.89 (95% CI: 0.88-0.90). Patients diagnosed first with breast carcinoma in situ and then with invasive breast cancer had a 5-year net survival of 0.92 (95% CI: 0.85-1.01). CONCLUSION: Invasive breast tumours that were preceded by a breast carcinoma in situ were detected more frequently at an earlier stage, compared to those that were not. The estimated 5-year net survival of patients with breast tumours was good.

Time-trends and age and stage differences in 5-year relative survival for common cancer types by sex in the canton of Zurich, Switzerland.

BACKGROUND: Survival trends help to evaluate the progress made to reduce the burden of cancer. The aim was to estimate the trends in 5-year relative survival of patients diagnosed with breast, prostate, lung, colorectal cancer and skin melanoma in the time periods 1980-1989, 1990-1999, 2000-2009 and 2010-2015 in the Canton of Zurich, Switzerland. Furthermore, we investigated relative survival differences by TNM stage and age group. METHODS: Data from the Cancer Registry of Zurich was used from 1980 to and including 2015, including incident cases of breast (N = 26,060), prostate (N= 23,858), colorectal (N= 19,305), lung cancer (N= 16,858) and skin melanoma (N= 9780) with follow-up until 31 December 2020. The cohort approach was used to estimate 5-year relative survival. RESULTS: The 5-year relative survival increased significantly between 1980 and 1989, and 2010 and2015: from 0.70 to 0.89 for breast, from 0.60 to 0.92 for prostate, from 0.09 to 0.23 (men) and from 0.10 to 0.27 (women) for lung, from 0.46 to 0.66 (men) and from 0.48 to 0.68 (women) for colorectal cancer, and from 0.74 to 0.94 (men) and from 0.86 to 0.96 (women) for skin melanoma. Survival for stage IV tumors was considerably lower compared to lower-staged tumors for all cancer types. Furthermore, relative survival was similar for the age groups <80 years but lower for patients aged 80 years and older. CONCLUSION: The observed increasing trends in survival are encouraging and likely reflect raised awareness around cancer, improved diagnostic methods, and improved treatments. The fact that stage I tumor patients have generally high relative survival reflects the efforts made regarding early detection.

Retrospective analysis of the uptake of active surveillance for low-risk prostate cancer in Zurich, Switzerland.

OBJECTIVES: Active surveillance for low-risk prostate cancer closely monitors patients conservatively instead of the pursuit of active treatment to reduce overtreatment of insignificant disease. Since 2009, active surveillance has been recommended as the primary management option in the European Association of Urology guidelines for low-risk disease. The present study aimed to investigate the use and uptake of active surveillance over 10 years in our certified prostate cancer centre (University Hospital of Zurich) compared with those derived from the cancer registry of the canton of Zurich, Switzerland. MATERIALS AND METHODS: We retrospectively identified all men diagnosed with low-risk prostate cancer at our institution and from the cancer registry of the canton of Zurich from 2009 to 2018. The primary treatment of each patient was recorded. Descriptive statistics were used to analyze the use of different treatments in our centre. The results were compared with those derived from the cancer registry. RESULTS: A total of 3393 men with low-risk prostate cancer were included in this study (University Hospital of Zurich: n = 262; cancer registry: n = 3131). In the University Hospital of Zurich and cancer registry cohorts, 146 (55.7%) and 502 (16%) men underwent active surveillance, respectively. The proportions of local treatment [115 (43.9%) vs 2220 (71%)] and androgen deprivation therapy [0 (0%) vs 43 (1.4%)] were distinctly lower in the University Hospital of Zurich cohort than in the cancer registry cohort. The uptake of active surveillance over the years was high in the University Hospital of Zurich cohort (35.4% in 2009 and 88.2% in 2018) but only marginal in the cancer registry cohort (12.2% in 2009 and 16.2% in 2018). CONCLUSION: Despite clear guideline recommendations, active surveillance for low-risk prostate cancer is still widely underused. Our analysis showed that access to a certified interdisciplinary tumour board significantly increases the use of active surveillance.

Extranodal diffuse large B cell lymphoma of cutaneous follicle centre lymphoma type: a study of 24 patients with non-cutaneous primary limited stage extranodal diffuse large B cell lymphoma in support of a new concept.

AIMS: Follicle centre cell lymphoma of small cell type showing either a follicular or diffuse growth pattern similar to cutaneous follicle centre lymphoma (cFCL) has been recognized in extranodal non-cutaneous sites. Our aim was (i) to investigate whether diffuse large B cell lymphoma (DLBCL) of cFCL type could be identified in extranodal non-cutaneous sites and (ii) whether clinical characteristics similar to primary cFCL could be recognized. METHODS AND RESULTS: Of 24 extranodal non-cutaneous DLBCLs, nine (38%) had large centrocytoid morphology and 15 (62%) were either 'centrocytoid and centroblastic' or 'centroblastic and immunoblastic'. Six centrocytoid cases were Irf-4 negative, Bcl-6 positive and at most weakly CD10- or Bcl-2-positive by immunohistochemistry, consistent with DLBCL of cFCL type. All patients with cFCL type were stage IE and were significantly younger than other patients. Recurrences occurred in two patients and were exclusively extranodal. CONCLUSION: Our results suggest that DLBCL of cFCL type can be identified in extranodal non-cutaneous sites and shows clinical characteristics similar to genuine cFCL. We propose to expand the concept of cFCL to encompass large cell lymphomas in extranodal sites.

Is Season of Diagnosis a Predictor of Cancer Survival? Results from the Zurich Cancer Registry.

In Switzerland, there is a large seasonal variation in sunlight, and vitamin D deficiency is relatively common during winter. The season of diagnosis may be linked to cancer survival via vitamin D status. Using data from the Cancer Registry of Zurich, Zug, Schaffhausen, and Schwyz with more than 171,000 cancer cases registered since 1980, we examined the association of the season of diagnosis with survival for cancers including prostate (ICD10 code C61; International Categorization of Diseases, version 10), breast (C50), colorectal (C18-21), lung (C34), melanoma (C43), and all sites combined. Cox proportional hazards regression models were used to assess the differences in the all-cause mortality by the season of the diagnosis. Winter was used as the reference season. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for all the cancers combined (excluding nonmelanoma skin cancer) and for prostate (in men), breast (in women), colorectal, lung cancer, and melanomas, separately. A diagnosis in summer and/or autumn was associated with improved survival in all the sites combined for both sexes (men: HR 0.97 [95% CI 0.96-0.99]; women: HR 0.97 [95% CI 0.94-0.99]) and in colorectal (HR 0.91 [95% CI 0.84-0.99]), melanoma (HR 0.81 [95% CI 0.65-1.00]), and breast cancer (HR 0.91 [95% CI 0.94-0.99]) in women. Our study results suggest that a cancer diagnosis in summer and/or autumn is associated with a better prognosis. The improved seasonal survival coincides with the seasonal variation of sun-induced vitamin D, and vitamin D may play a protective and beneficial role in cancer survival.

Incidence and mortality trends of thyroid cancer from 1980 to 2016.

AIMS OF THE STUDY: Thyroid cancer incidence rates have been increasing globally over past decades. However, no study examining those trends in the canton of Zurich, Switzerland exists. In this study, we describe the incidence and mortality trends of thyroid cancer in the canton of Zurich during a 37-year period (1980-2016) including factors such as sex, histological subtypes and age at diagnosis. METHODS: We analysed population-based cancer registry data from 1980-2016 for the canton of Zurich, Switzerland. We estimated the age-standardised incidence and mortality rates using the European standard population. Joinpoint regression was used to detect average annual percentage changes (AAPCs) and their corresponding 95% confidence intervals (CIs). RESULTS: We included 2972 primary cases of thyroid cancer (72.3% in women). The papillary cases accounted for the majority of incident cases (65.8%). In 2016, women had a higher age-standardised incidence rate than men for both papillary (10.4 and 3.3, respectively, per 100,000) and non-papillary (1.6 and 0.7, respectively, per 100,000) thyroid cancer. In both men and women, the incidence rates of thyroid cancer increased significantly over the study period with AAPCs of 1.4% (95% CI 0.6-2.2%) and 2.6% (95% CI 2-3.1%), respectively. These increasing incidence trends are mainly driven by papillary thyroid cancer with AAPCs of 3.4% in men (95% CI 2.3% to 4.4%) and 4.3% in women (95% CI 3.7% to 5%). Mortality rates significantly decreased in both sexes (men AAPC -3.6%, 95% CI -4.7% to -2.4%; women AAPC -3.7%, 95% CI -4.8% to -2.6%). CONCLUSIONS: Our results show significantly increasing age-standardised incidence rates of thyroid cancer over time in both sexes, mainly due to papillary thyroid cancer, the most frequent histological subtype, and the only subtype for which a significant increase was observed. It is possible that many indolent thyroid cancers, and more specifically papillary microcarcinomas, are increasingly diagnosed, which may not lead to symptoms if undetected. Therefore, targeted diagnostic strategies are necessary to avoid overdiagnosis of thyroid cancer. Nevertheless, we cannot completely exclude a partly true increase.

Risk for Invasive Cancers in Women With Breast Cancer In Situ: Results From a Population Not Covered by Organized Mammographic Screening.

BACKGROUND: Even though breast cancer in situ (BCIS) incidence has been increasing, the prognosis of BCIS patients has not been extensively investigated. According to the literature, women with BCIS have a higher risk of developing subsequent invasive breast cancer; conflicting information has been reported regarding their potential risk for a subsequent invasive non-breast cancer. METHODS: Data from 1,082 women, whose first-ever cancer diagnosis was primary BCIS between 2003 and 2015 and were living in the canton of Zurich, were used. Standardized incidence ratios (SIRs) were calculated to compare the risk of an invasive breast or non-breast cancer among women with a primary BCIS with the corresponding risk of the adult female population. SIRs were calculated overall and by patient and tumor characteristics. To investigate potential risk factors (e.g., age at diagnosis, treatment) for a subsequent invasive breast or non-breast cancer we used Cox proportional hazards regression models. RESULTS: BCIS patients had 6.85 times [95% confidence interval (CI): 5.52-8.41] higher risk of being diagnosed with invasive breast cancer compared to the general population. They additionally faced 1.57 times (95% CI: 1.12-2.12) higher risk of an invasive non-breast cancer. The SIRs were higher for women < 50-years old for both invasive breast and non-breast cancer at BCIS diagnosis. Age ≥ 70-years old at BCIS diagnosis was statistically significantly associated with a subsequent invasive non-breast cancer diagnosis. CONCLUSIONS: BCIS patients had a higher risk of being diagnosed with invasive breast and non-breast cancer compared to the general population. Age 70 years or older at BCIS diagnosis was the only risk factor statistically significantly associated with a subsequent invasive non-breast cancer. Our results support the increased risk for subsequent cancers in BCIS patients reported in the literature. Future studies should establish the risk factors for subsequent cancers, highlight the need for intensive monitoring in this population, and help distinguish BCIS patients who could benefit from systemic therapy to prevent distant cancers.

Impact of comorbidities at diagnosis on the 10-year colorectal cancer net survival: A population-based study.

BACKGROUND: It is established that comorbidities negatively influence colorectal cancer (CRC)-specific survival. Only few studies have used the relative survival (RS) setting to estimate this association, although RS has been proven particularly useful considering the inaccuracy in death certification. This study aimed to investigate the impact of non-cancer comorbidities at CRC diagnosis on net survival, using cancer registry data. METHODS: We included 1076 CRC patients diagnosed between 2000 and 2001 in the canton of Zurich. The number and severity of comorbidities was expressed using the Charlson Comorbidity Index (CCI). Multiple imputation was performed to account for missing information and 10-year net survival was estimated by modeling the excess hazards of death due to CRC, using flexible parametric models. RESULTS: After imputation, approximately 35 % of the patients were affected by comorbidities. These appeared to decrease the 10-year net survival; the estimated excess hazard ratio for patients with one mild comorbidity was 2.14 (95 % CI 1.60-2.86), and for patients with one more severe or more than one comorbidity was 2.43 (95 % CI 1.77-3.34), compared to patients without comorbidities. CONCLUSIONS: Our analysis suggested that non-cancer comorbidities at CRC diagnosis significantly decrease the 10-year net survival. Future studies should estimate net survival of CRC including comorbidities as prognostic factor and use a RS framework to overcome the uncertainty in death certification.

Are there sex differences among colorectal cancer patients in treatment and survival? A Swiss cohort study.

BACKGROUND: Colorectal cancer (CRC) is among the three most common incident cancers and causes of cancer death in Switzerland for both men and women. To promote aspects of gender medicine, we examined differences in treatment decision and survival by sex in CRC patients diagnosed 2000 and 2001 in the canton of Zurich, Switzerland. METHODS: Characteristics assessed of 1076 CRC patients were sex, tumor subsite, age at diagnosis, tumor stage, primary treatment option and comorbidity rated by the Charlson Comorbidity Index (CCI). Missing data for stage and comorbidities were completed using multivariate imputation by chained equations. We estimated the probability of receiving surgery versus another primary treatment using multivariable binomial logistic regression models. Univariable and multivariable Cox proportional hazards regression models were used for survival analysis. RESULTS: Females were older at diagnosis and had less comorbidities than men. There was no difference with respect to treatment decisions between men and women. The probability of receiving a primary treatment other than surgery was nearly twice as high in patients with the highest comorbidity index, CCI 2+, compared with patients without comorbidities. This effect was significantly stronger in women than in men (p-interaction = 0.010). Survival decreased with higher CCI, tumor stage and age in all CRC patients. Sex had no impact on survival. CONCLUSION: The probability of receiving any primary treatment and survival were independent of sex. However, female CRC patients with the highest CCI appeared more likely to receive other therapy than surgery compared to their male counterparts.

AID protein expression in chronic lymphocytic leukemia/small lymphocytic lymphoma is associated with poor prognosis and complex genetic alterations.

The biological behavior of chronic lymphocytic leukemia and small lymphocytic lymphoma is unpredictable. Nonetheless, non-mutated IgV(H) gene rearrangement, ATM (11q22-23) and p53 (17p13) deletion are recognized as unfavorable prognosticators in chronic lymphocytic leukemia. The mRNA expression of activation-induced cytidine deaminase (AID), an enzyme indispensable for somatic hypermutation processes, was claimed to be predictive of non-mutated chronic lymphocytic leukemia cells in blood. Here, we evaluated AID protein expression compared with known molecular and immunohistochemical prognostic indicators in 71 chronic lymphocytic leukemia/small lymphocytic lymphoma patients using a tissue microarray approach. We found AID heterogeneously expressed in tumor cells as shown by colocalization analysis for CD5 and CD23. Ki-67 positive paraimmunoblasts of the proliferation centers displayed the highest expression. This observation is reflected by a significant association of AID positivity with a high proliferation rate (P=0.012). ATM deletion was detected in 10% (6/63) of patients and p53 deletion in 19% (13/67) of patients. Moreover, both ATM (P=0.002) and p53 deletion (P=0.004) were significantly associated with AID. IgV(H) gene mutation was seen in 45% (27/60) of patients. Twenty-five percent (17/69) of patients with AID-positive chronic lymphocytic leukemia/small lymphocytic lymphoma displayed a shorter survival than AID-negative chronic lymphocytic leukemia/small lymphocytic lymphoma patients (61 vs 130 months, P=0.001). Although there was a trend, we could not show an association with the IgV(H) gene mutation status. Taken together, our study shows that AID expression is an indicator of an unfavorable prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma patients, although it is not a surrogate marker for the IgV(H) status. Furthermore, the microenvironment of proliferation centers seems to influence AID regulation and might be an initiating factor in its transformation.

37-year incidence and mortality time trends of common cancer types by sex, age, and stage in the canton of Zurich.

AIMS OF THE STUDY: The Cancer Registry Zurich, Zug, Schaffhausen and Schwyz is one of the oldest cancer registries in Switzerland, first registering tumours in 1980 for the canton of Zurich. The aim of this study was to analyse trends in incidence and mortality for the most common types of cancer in the canton of Zurich from 1981 to 2017. METHODS: In this analysis of population-based cancer registry data, we included malignant tumours of the breast (ICD10 C50), prostate (C61), colon/rectum (C18–C21), lung (C33–C34), and melanoma (C43), diagnosed between 1981 and 2017. Age-standardised incidence and mortality rates per 100,000 person-years were computed using the 1976 European Standard Population. Incidence and mortality time trends were assessed using joinpoint regression analysis. RESULTS: In men, incidence for prostate cancer and melanoma increased over the study period, while it decreased for colon/rectum and lung cancer. A joinpoint for prostate cancer indicated the start of a decreasing trend in 2002. In women, incidence increased for breast cancer, lung cancer and melanoma; no trend was observed for colon/rectum cancer. Cancer mortality decreased for prostate, colon/rectum and lung cancer in men, with no clear trend for melanoma. In women, mortality decreased for breast cancer, colon/rectum cancer and melanoma, but increased for lung cancer. CONCLUSIONS: The overall increasing incidence trends for prostate and breast cancer, as well as for melanoma, are in line with data from other Western countries. While lung cancer incidence is decreasing in men, it is still on the rise in women. Despite increasing incidence rates, mortality rates are decreasing for all localisations except for lung cancer in women. The opposite direction of incidence and mortality curves is probably mostly due to better and more effective treatment options, as well as earlier detection.

Increasing trends in in situ breast cancer incidence in a region with no population-based mammographic screening program: results from Zurich, Switzerland 2003-2014.

PURPOSE: Increase in in situ breast cancer (BCIS) incidence has been reported across Europe and the USA. However, little is known about the trends in BCIS incidence in regions without population-based mammographic screening programs. We set out to investigate these trends in Zurich, Switzerland, where only opportunistic mammographic screening exists. METHODS: Data from 989 women diagnosed with a primary BCIS between 2003 and 2014 were used in our analyses. Age-standardized incidence rates per 100,000 person-years (ASR) were computed per year. Additional analyses by BCIS subtype, by age group at diagnosis and by incidence period were conducted. Incidence trends over time were assessed using joinpoint regression analysis. RESULTS: The overall BCIS ASR was 10.7 cases per 100,000 person-years with an increasing trend over the study period. A similar trend was observed for the ductal carcinoma in situ (DCIS) ASR, while the lobular carcinoma in situ (LCIS) ASR decreased. Age-specific analyses revealed that the 50-59 year age group had the highest BCIS ASR. The highest increase in BCIS ASR, even though not statistically significant, was observed for the < 40 year age group. CONCLUSIONS: BCIS ASR increased linearly over a 12-year period. The increase was reflected by an increase in DCIS ASR, whereas LCIS ASR decreased over time. The highest increase in BCIS ASR over the study period was observed for the < 40 year age group, even though not statistically significant. Patient and tumor characteristics of this group that may be associated with BCIS development warrant further investigation.

Indicators of Data Quality at the Cancer Registry Zurich and Zug in Switzerland.

Data quality is an important issue in cancer registration. This paper provides a comprehensive overview of the four main data quality indicators (comparability, validity, timeliness, and completeness) for the Cancer Registry Zurich and Zug (Switzerland). We extracted all malignant cancer cases (excluding non-melanoma skin cancer) diagnosed between 1980 and 2014 in the canton of Zurich. Methods included the proportion of morphologically verified cases (MV%), the proportion of DCN and DCO cases (2009-2014), cases with primary site uncertain (PSU%), the stability of incidence rates over time, age-specific incidence rates for childhood cancer, and mortality:incidence (MI) ratios. The DCO rate decreased from 6.4% in 1997 to 0.8% in 2014 and was <5% since 2000. MV% was 95.5% in 2014. PSU% was <3% over the whole period. The incidence rate of all tumours increased over time with site-specific fluctuations. The overall M:I ratio decreased from 0.58 in 1980 to 0.37 in 2014. Overall, data quality of the Cancer Registry Zurich and Zug was acceptable according to the methods presented in this review. Most indicators improved over time with low DCO rates, high MV%, low PSU%, relatively low M:I ratios and age-specific incidence of childhood cancer within reference ranges.

The risk of prostate cancer mortality and cardiovascular mortality of nonmetastatic prostate cancer patients: A population-based retrospective cohort study.

PURPOSE: To assess the risk of prostate cancer (PCa) specific mortality (PCSM) compared to cardiovascular disease mortality (CVDM), or other-cause mortality (OCM) of men with nonmetastatic PCa according to PCa risk groups, primary treatment, and age. PATIENTS AND METHODS: This retrospective population-based cohort study identified 1,908 nonmetastatic PCa patients in the cancer registry Zurich and Zug, diagnosed between 2000 and 2009 living in the City of Zurich. Multiple imputation methods were applied to handle missing PCa information. Fine and Gray competing risk regression analysis was used to estimate subdistribution hazard ratios for the outcomes PCSM, CVDM, or OCM RESULTS: Ten years after diagnosis the cumulative probability of PCSM and CVDM was 16.4% and 10.0%, respectively. We observed an increased adjusted risk of PCSM in men treated with androgen deprivation therapy (ADT) compared to surgery, but could not observe an association between ADT and CVDM. The probability of PCSM was significantly higher for patients on active surveillance or watchful waiting, compared to surgery. Age and PCa risk categories were positively associated with risk of PCSM, whereas there was no evidence for an association with CVDM or OCM based on risk groups. CONCLUSIONS: Overall, men with PCa were more likely to die from non-PCa related outcomes. Nevertheless, the analyses showed a high proportion of PCSM among men on ADT, older men and men with a high-risk tumor. However, further research is needed to understand comprehensively the benefits of the respective treatments.