Breast cancer incidence and survival: registry-based studies of long-term trends and determinants

__Abstract__ Breast cancer is the most frequent cancer among women in the Netherlands, and it is the most important cause of cancer death. Between age 35 and 55 about 20% of all deaths among women is due to breast cancer.1 The age-standardised incidence rate is among the highest in Europe/ and incidence rates have been increasing since 1960.3 The mortality from breast cancer has been fairly stable for many years, but decreased somewhat in the last decade (figure 1). The detection of (early) breast cancer has been facilitated by the introduction and increased use of mammography and cytology since the 1980s. The implementation of the mass breast cancer screening programme between 1991 and 1996 further increased the incidence of breast cancer, also because of an increased awareness in the population. However, any increase associated with early detection would be temporary. Some of the screen-detected tumours would never have been diagnosed without a mass screening programme, so some of the increase is likely to be artificial

Increase of sentinel lymph node melanoma staging in The Netherlands; still room and need for further improvement

Aim: To investigate implementation of the seventh American Joint Committee on Cancer melanoma staging with sentinel lymph node biopsy (SLNB) and associations with socioeconomic status (SES). Patients & methods: Data from The Netherlands Cancer Registry on patient and tumor characteristics were analyzed for all stage IB-II melanoma cases diagnosed 2010-2016, along with SES data from The Netherlands Institute for Social Research. Results: The proportion of SLNB-staged patients increased from 40% to 65% (p <0.001). Multivariate analysis showed that being female, elderly, or having head-and-neck disease reduced the likelihood of SLNB staging. Conclusion: SLNB staging increased by 25% during the study period but lagged among elderly patients and those with head-and-neck melanoma. In The Netherlands, SES no longer affects SLNB staging performance

Cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas stratified for patients with organ transplantation and hematologic malignancies:A nationwide cohort study

Background: There is lack of nationwide data on the cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas (cSCCs) among patients with a first cSCC. Objective: To investigate the cumulative incidence and timing of subsequent cSCCs. Methods: Patients with a first cSCC in 2007/2008 from the Netherlands Cancer Registry were linked to the Netherlands Pathology Registry for subsequent cSCCs and the Netherlands Organ Transplant Registry. Cumulative incidence function curves were calculated for subsequent cSCCs and stratified for immune status. Results: Among the 12,345 patients, second to sixth cSCC occurred in 4325, 2010, 1138, 739, and 501 patients, with median time intervals of 1.4, 1.2, 0.9, 0.6, and 0.5 years after the previous cSCC, respectively. The cumulative incidence of a subsequent cSCC at 5 years increased from 28% to 67% for the second to sixth cSCC. For solid organ transplant recipients, the cumulative incidences increased from 74% to 92% and from 41% to 64% for patients with hematologic malignancy. Limitations: Only histopathologically confirmed cSCCs were included. Conclusion: The risk of a subsequent cSCC steeply rises with the number of prior cSCCs and immune status, while the time interval decreases. This can support more informed decisions about follow-up management.</p

Cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas stratified for patients with organ transplantation and hematologic malignancies:A nationwide cohort study

Background: There is lack of nationwide data on the cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas (cSCCs) among patients with a first cSCC. Objective: To investigate the cumulative incidence and timing of subsequent cSCCs. Methods: Patients with a first cSCC in 2007/2008 from the Netherlands Cancer Registry were linked to the Netherlands Pathology Registry for subsequent cSCCs and the Netherlands Organ Transplant Registry. Cumulative incidence function curves were calculated for subsequent cSCCs and stratified for immune status. Results: Among the 12,345 patients, second to sixth cSCC occurred in 4325, 2010, 1138, 739, and 501 patients, with median time intervals of 1.4, 1.2, 0.9, 0.6, and 0.5 years after the previous cSCC, respectively. The cumulative incidence of a subsequent cSCC at 5 years increased from 28% to 67% for the second to sixth cSCC. For solid organ transplant recipients, the cumulative incidences increased from 74% to 92% and from 41% to 64% for patients with hematologic malignancy. Limitations: Only histopathologically confirmed cSCCs were included. Conclusion: The risk of a subsequent cSCC steeply rises with the number of prior cSCCs and immune status, while the time interval decreases. This can support more informed decisions about follow-up management.</p

Educational inequalities in cancer survival: A role for comorbidities and health behaviours?

Aim: To describe educational inequalities in cancer survival and to what extent these can be explained by comorbidity and health behaviours (smoking, physical activity and alcohol consumption). Methods: The GLOBE study sent postal questionnaires to individuals in The Netherlands in 1991 resulting in 18 973 respondents (response 70%). Questions were asked on education, health and health-related behaviours. Participants were linked for cancer diagnosis (1991-2008), comorbidity and survival (up to 2010) with the population-based Eindhoven Cancer Registry; 1127 tumours were included in the analyses. Results: 5-year crude survival was best in highly educated patients as compared with low educated patients for all cancers combined: 49% versus 32% in male subjects (log rank: p<0.0001), 65% versus 49% in female subjects (p=0.0001). Compared with highly educated, low educated prostate cancer patients had an increased risk of death (HR 2.9 (95% CI 1.7 to 5.1), adjusted for age, stage and year). No or inconsistent associations between educational level and risk of death were seen in multivariable analyses for breast, colon and non-small cell lung cancer. Although survival in prostate cancer patients was affected by comorbidities (HR2_vs_0_comorbidities: 2.6 (1.5 to 4.4)), physical activity (HRno/little_vs__moderate_physical__activity: 2.0 (1.2 to 3.4)) and smoking (HRcurrent_vs_never_smokers: 2.6 (1.0-6.8)), these did not contribute to educat

Primary Melanoma Characteristics of Metastatic Disease:A Nationwide Cancer Registry Study

The characteristics and disease patterns of primary stage I and II cutaneous melanomas that progress to stage III or IV disease were investigated based on data from the Netherlands Cancer Registry (NCR). Data on stage III or IV melanomas at first diagnosis or during follow-up between 2017 and 2019 were retrieved. Patient and primary tumour characteristics were investigated in relation to time to disease progression and the number of organ sites with metastatic disease using regression models. In total, 2763 patients were included, of whom 1613 were diagnosed with stage IV disease. Among the patients with stage IV disease, 60% (n = 963) were initially diagnosed with stage I or II disease. The proportion of patients who received a sentinel lymph node biopsy increased after the introduction of adjuvant therapy in 2019 from 61% to 87%. Among all patients with stage III disease who were eligible for adjuvant systemic therapy (n = 453) after 2019, 37% were not treated with this therapy. Among patients with stage IV disease, lung metastases were most often detected as the first metastatic site and females presented with more metastatic sites than males. Most patient and primary tumour characteristics were not associated with the distant metastatic organ site, except melanoma localisation in the lower extremities and the head or neck. Our observation that most stage IV patients were initially diagnosed with early-stage disease highlights the need for more accurate risk prediction models

The risk of cutaneous squamous cell carcinoma among patients with type 2 diabetes receiving hydrochlorothiazide:A cohort study

Background: Because of continuous hyperglycemia and hyper-insulinemia and the use of photosensitizing drug, hydrochlorothiazide (HCTZ), the risk of cutaneous squamous cell carcinoma (cSCC) might be increased among patients with diabetes. This study aimed to estimate the risk of cSCC among HCTZ users with type 2 diabetes, and to determine whether thiazide-like diuretics, another drug in the same class with HCTZ, would be safer. Methods: We linked the benchmarking database in Dutch primary care, the Netherlands Cancer Registry, and the Dutch Personal Records Database (1998-2019). All 71,648 patients were included, except for those who had a history of skin cancer prior to cohort entry. We used Cox modeling to estimate the HRs and 95% confidence intervals for cSCC. The model was adjusted by cumulative exposure to each antihypertensive, age, sex, smoking, body mass index, blood pressure, serum creatinine, other confounding drug use at cohort entry, and cohort entry year. Results: There were 1,409 cSCC events (23 among thiazide-like diuretics users), during a follow-up of 679,789 person-years. Compared with no HCTZ use, the adjusted HRs for HCTZ use were 1.18 (1.00-1.40) for ≤2 years, 1.57 (1.32-1.88) for 2 to 4 years, and 2.09 (1.73-2.52) for >4 years. The HR was 0.90 (0.79-1.03) for an additional year of thiazide-like diuretic use. Conclusions: In patients with diabetes, exposure to HCTZ for >2 years is associated with an increased risk of cSCC, whereas no increased risk associated with thiazide-like diuretics was observed. Impact: The potential increased risk of cSCC should be a consideration when prescribing HCTZ, with thiazide-like diuretics offering a safer alternative

Small but significant socioeconomic inequalities in axillary staging and treatment of breast cancer in the Netherlands

Background: The use of sentinel node biopsy (SNB), lymph node dissection, breast-conserving surgery, radiotherapy, chemotherapy and hormonal treatment for breast cancer was evaluated in relation to socioeconomic status (SES) in the Netherlands, where access to care was assumed to be equal. Methods: Female breast cancer patients diagnosed between 1994 and 2008 were selected from the nationwide population-based Netherlands Cancer Registry (N=176 505). Socioeconomic status was assessed based on income, employment and education at postal code level. Multivariable models included age, year of diagnosis and stage. Results: Sentinal node biopsy was less often applied in high-SES patients (multivariable analyses, ≤49 years: odds ratio (OR) 0.70 (95% CI: 0.56-0.89); 50-75 years: 0.85 (0.73-0.99)). Additionally, lymph node dissection was less common in low-SES patients aged ≥76 years (OR 1.34 (0.95-1.89)). Socioeconomic status-related differences in treatment were only significant in the age group 50-75 years. High-SES women with stage T1-2 were more likely to undergo breast-conserving surgery (radiotherapy) (OR 1.15 (1.09-1.22) and OR 1.16 (1.09-1.22), respectively). Chemotherapy use among node-positive patients was higher in the high-SES group, but was not significant in multivariable analysis. Hormonal therapy was not related to SES. Conclusion: Small but significant differences were observed in the use of SNB, lymph node dissection and breast-conserving surgery according to SES in Dutch breast cancer patients despite assumed equal access to health care

Melanoma in older patients: declining gap in survival between younger and older patients with melanoma

Background: Older people have the highest incidence of melanoma and the population in most Western countries is ageing. We evaluated how the gap in incidence and survival between younger and older patients has developed during the past decades.Material and methods: All patients diagnosed with cutaneous melanoma between 1989 and 2015 (n = 84,827) were identified from the Netherlands Cancer Registry. Elderly were defined as aged ≥70 years. Differences in patient and tumor characteristics were described, age-specific incidence rates were calculated, and relative survival (RS) and multivariable analyses estimating the Relative Excess Rate of dying (RER) were conductedResults: In older men, the melanoma age-standardized incidence increased from 18 to 103/100,000 person-years (py) between 1989 and 2015 and in older women from 23 to 70/100,000 py. In younger men and women, it increased from 8 to 21 and from 13 to 28/100,000 py, respectively. Median Breslow thickness declined from 1.8 to 1.1 mm and from 1.6 to 1.1 mm in older men and women (2003 versus 2015), and from 1.1 to 0.9 mm and 0.9 to 0.8 mm in younger men and women. In older men, 5-year RS increased from 67% (95% CI: 63%-72%) in 1989-1997 to 85% (95% CI: 83%-87%) in 2007-2015 and in older women from 81% (95% CI: 78%-85%) to 89% (95% CI: 87%-91%). In younger men and women, RS increased from 82% (95% CI: 81%-83%) to 90% (95% CI: 90%-91%) and from 92% (95% CI: 92%-93%) to 96% (95% CI: 95%-96%). After case-mix correction , older men and women no longer showed an improved survival over time (RER 2010-2015 versus 2003-2009: 0.97; 95% CI: 0.81-1.16 and 0.95; 95% CI: 0.79-1.16). Whereas in younger men and women survival remained improved (RER 0.75; 95% CI: 0.67-0.83 and 0.77; 95%CI: 0.67-0.89).Conclusion: The gap in melanoma incidence between younger and older peopl

Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

Background:Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens.Methods:In a Dutch cohort of 3121 5-year HL survivors treated between 1965 and 1995, subsite-specific CRC incidence was compared with general population rates. Treatment effects were quantified by Cox regression analyses.Results:After a median follow-up of 2