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Melanoma of unknown primary (MUP) may have a different biology to melanoma of known primary, but clinical trials of novel therapies (e.g., immune checkpoint or BRAF/MEK inhibitors) have not reported the outcomes in this population. We therefore evaluated the overall survival (OS) among patients with MUP in the era of novel therapy. Data for stage III or IV MUP were extracted from a nationwide database for the period 2003–2016, with classification based on the eighth edition of the American Joint Committee on Cancer criteria. The population was divided into pre‐ (2003–2010) and post‐ (2011–2016) novel therapy eras. Also, OS in the post‐novel era was compared between patients with stage IV MUP by whether they received novel therapy. In total, 2028 of 65,110 patients (3.1%) were diagnosed with MUP. Metastatic sites were known in 1919 of 2028 patients, and most had stage IV disease (53.8%). For patients with stage III MUP, the 5‐year OS rates were 48.5% and 50.2% in the pre‐ and post‐novel eras, respectively (p = 0.948). For those with stage IV MUP, the median OS durations were unchanged in the pre‐novel era and post‐novel era when novel therapy was not used (both 4 months); however, OS improved to 11 months when novel therapy was used in the post‐novel era (p < 0.001). In conclusion, more than half of the patients with MUP are diagnosed with stage IV and the introduction of novel therapy appears to have significantly improved the OS of these patients. What's new? Melanoma of unknown primary (MUP) site may have a different biology to melanoma of known primary, but clinical trials of novel therapies (e.g., immune checkpoint or BRAF/MEK inhibitors) have not reported the outcomes in this population. Knowledge about outcomes could however aid clinical management of patients with MUP. In this nationwide study from 2003 to 2016, the authors show that the introduction of novel therapy has significantly improved the overall survival for patients with stage IV melanoma of unknown primary, who represented more than half of the patients diagnosed with MUP in the Netherlands. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In the present study, we investigated whether age and serious comorbid conditions influence treatment decisions, complications and survival in breast cancer patients. The Eindhoven Cancer Registry records patient, tumour and therapy characteristics of all patients diagnosed with cancer in the southern part of the Netherlands. Additional information on severity of comorbidity and serious complications was collected for a random sample of 527 breast cancer patients (aged 40 years and older). More than 70% of the patients ?80 exhibited high severity of comorbidity compared to 6% of those aged 40-49 years. Treatment was not influenced by severity of comorbidity. Less than 30% of the breast cancer patients had complications after diagnosis. The number of complications was not related to age or severity of comorbidity. The hazard ratio (HR) of dying for patients with low/moderate severity of comorbidity was 2.4 for those aged 40-69 years and 1.6 for those aged ?70 years, after adjustment for age, nodal status and treatment. For patients with high severity of comorbidity, the risk of dying was almost three times higher. Older breast cancer patients with serious comorbidity were not treated differently and did not have more complications compared to those without comorbidity, but they exhibited a worse prognosis.British Journal of Cancer (2004) 90, 2332-2337. doi:10.1038/sj.bjc.6601844 www.bjcancer.com Published online 25 May 2004 [ABSTRACT FROM AUTHOR]

Background: The Multicenter Selective Lymphadenectomy Trial (MSLT-1) comparing survival after a sentinel lymph node biopsy (SLNB) versus nodal observation in melanoma patients did not show a significant benefit favoring SLNB. However, in subgroup analyses melanoma-specific survival among patients with nodal metastases seemed better., Aim: To evaluate the association of performing a SLNB with overall survival in intermediate thickness melanoma patients in a Dutch population-based daily clinical setting., Methods: Survival, excess mortality adjusted for age, gender, Breslow-thickness, ulceration, histological subtype, location, co-morbidity and socioeconomic status were calculated in a population of 1,989 patients diagnosed with malignant cutaneous melanoma (1.2-3.5 mm) on the trunk or limb between 2000-2016 in ten hospitals in the South East area, The Netherlands., Results: A SLNB was performed in 51% of the patients (n = 1008). Ten-year overall survival after SLNB was 75% (95%CI, 71%-78%) compared to 61% (95%CI 57%-64%) following observation. After adjustment for risk factors, a lower risk on death (HR = 0.80, 95%CI 0.66-0.96) was found after SLNB compared to observation only., Conclusions: SLNB in patients with intermediate-thickness melanoma on trunk or limb resulted in a 14% absolute and significant 10-year survival difference compared to those without SLNB., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The 8th American Joint Committee on Cancer (AJCC) staging edition includes revisions regarding pT1 melanomas. We aimed to evaluate the expected impact of this edition on staging and survival in the Dutch pT1 melanoma population., Methods: In total, 32,935 pT1 melanoma patients, whose data were retrieved from the Netherlands Cancer Registry between 2003 and 2015, were included in the study. Patients were stratified by the 6th AJCC edition (cohort 1: 2003-2009) and 7th edition (cohort 2: 2010-2015) and all reclassified according to the 8th edition. Stage migration, sentinel lymph node biopsy (SLNB) positivity rates and relative survival were analysed. Agreement between staging systems was calculated by Cohen's kappa coefficient., Results: In cohort 2, restaging according to the 8th edition led to an increase of 7% in the total number of patients staged pT1b. The kappa score for agreement between the 6th and 8th edition was 0.15 and 0.25 for agreement between 7th and 8th edition. Restaging according to the 8th edition resulted in a higher SLNB positivity rate for pT1b patients than pT1a patients (8% versus 5%, p = 0.08). Relative survival curves were predominantly similar between the staging editions., Conclusions: Implementation of the 8th AJCC staging edition will presumably not have major impact on the total number of Dutch pT1b patients. Consequently, the number of patients eligible for SLNB would roughly remain similar. In terms of SLNB positivity, the selection of high-risk pT1 melanoma patients is likely to improve. In addition, the 8th edition criteria for pT1 melanoma seem more workable for pathologists., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Due to the lack of solid evidence for treatment benefit of Sentinel Lymph Node Biopsy (SLNB) as part of loco-regional surgical treatment of non-distant metastatic melanoma, there might be variation in surgical treatment strategies in the Netherlands. The objective of the current study was to assess differences in the performance of SLNB, in geographical regions in the Netherlands, of non-distant metastatic melanoma patients (American Joint Committee on Cancer (AJCC) stage I-III)., Materials and Methods: A total of 28 550 melanoma patients, diagnosed between 2005 and 2013, were included in this population based retrospective study. Data were retrieved from the Netherlands Cancer Registry (NCR). Treatment strategies in 8 regions of the Netherlands were compared according to stage, excluding patients with distant metastasis (AJCC stage IV)., Results: Throughout the Netherlands, there was substantial practice variation across the regions. The performance of SLNB in patients with clinically unsuspected lymph nodes and Breslow thickness >1.0 mm was significantly different between the regions. In a post hoc analysis, we observed that patients aged over 60 years, female patients and patients with a melanoma located in head and neck have lower odds to receive a SLNB., Conclusion: There is considerable loco-regional practice variation which cannot completely be explained by the patient and tumor characteristics, in the surgical treatment of non-distant metastatic melanoma patients in the Netherlands. Although national guidelines recommend considering SLNB in all patients with a melanoma thicker than 1 mm, only half of the patients received a SLNB. Future research should assess whether this practice variation leads to unwanted variations in clinical outcome., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aim: To provide insight into cancer registration coverage, data access and use in Europe. This contributes to data and infrastructure harmonisation and will foster a more prominent role of cancer registries (CRs) within public health, clinical policy and cancer research, whether within or outside the European Research Area., Methods: During 2010-12 an extensive survey of cancer registration practices and data use was conducted among 161 population-based CRs across Europe. Responding registries (66%) operated in 33 countries, including 23 with national coverage., Results: Population-based oncological surveillance started during the 1940-50s in the northwest of Europe and from the 1970s to 1990s in other regions. The European Union (EU) protection regulations affected data access, especially in Germany and France, but less in the Netherlands or Belgium. Regular reports were produced by CRs on incidence rates (95%), survival (60%) and stage for selected tumours (80%). Evaluation of cancer control and quality of care remained modest except in a few dedicated CRs. Variables evaluated were support of clinical audits, monitoring adherence to clinical guidelines, improvement of cancer care and evaluation of mass cancer screening. Evaluation of diagnostic imaging tools was only occasional., Conclusion: Most population-based CRs are well equipped for strengthening cancer surveillance across Europe. Data quality and intensity of use depend on the role the cancer registry plays in the politico, oncomedical and public health setting within the country. Standard registration methodology could therefore not be translated to equivalent advances in cancer prevention and mass screening, quality of care, translational research of prognosis and survivorship across Europe. Further European collaboration remains essential to ensure access to data and comparability of the results., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: To examine variation in time and place in axillary staging and treatment of patients with ductal carcinoma in situ (DCIS) of the breast., Methods: Trends in patients with DCIS recorded in the Eindhoven Cancer Registry diagnosed in 1991-2010 (n = 2449) were examined., Results: The use of breast conserving surgery (BCS) went from 17% to 67% in 1991-2010 and administration of radiotherapy after BCS increased to 89%. Axillary lymph node dissection decreased to almost 0%, while sentinel node biopsy was performed in 65% of patients in 2010. The proportion who underwent BCS varied between hospitals from 49% to 80%; the proportion without axillary staging ranged from 21% to 60%. Patients with screen-detected DCIS were more likely to receive BCS., Conclusion: There was considerable variation in the use of BCS, radiotherapy, and axillary staging of DCIS over time and between hospitals. Patients with DCIS were more likely to be treated with BCS if their disease was detected by screening., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Diagnostic surgical breast biopsies have several disadvantages, therefore, they should be used with hesitation. We determined time trends in types of breast biopsies for the workup of abnormalities detected at screening mammography. We also examined diagnostic delays., Methods: In a Dutch breast cancer screening region 6230 women were referred for an abnormal screening mammogram between 1 January 1997 and 1 January 2011. During two year follow-up clinical data, breast imaging-, biopsy-, surgery- and pathology-reports were collected of these women. Furthermore, breast cancers diagnosed >3 months after referral (delays) were examined, this included review of mammograms and pathology specimens to determine the cause of the delays., Results: In 41.1% (1997-1998) and in 44.8% (2009-2010) of referred women imaging was sufficient for making the diagnosis (P<0.0001). Fine-needle aspiration cytology decreased from 12.7% (1997-1998) to 4.7% (2009-2010) (P<0.0001), percutaneous core-needle biopsies (CBs) increased from 8.0 to 49.1% (P<0.0001) and surgical biopsies decreased from 37.8 to 1.4% (P<0.0001). Delays in breast cancer diagnosis decreased from 6.7 to 1.8% (P=0.003)., Conclusion: The use of diagnostic surgical breast biopsies has decreased substantially. They have mostly been replaced by percutaneous CBs and this replacement did not result in an increase of diagnostic delays.

Background: Testicular germ cell tumour (TGCT) patients are at increased risk of developing a contralateral testicular germ cell tumour (CTGCT). It is unclear whether TGCT treatment affects CTGCT risk., Methods: The risk of developing a metachronous CTGCT (a CTGCT diagnosed ≥6 months after a primary TGCT) and its impact on patient's prognosis was assessed in a nationwide cohort comprising 3749 TGCT patients treated in the Netherlands during 1965-1995. Standardised incidence ratios (SIRs), comparing CTGCT incidence with TGCT incidence in the general population, and cumulative CTGCT incidence were estimated and CTGCT risk factors assessed, accounting for competing risks., Results: Median follow-up was 18.5 years. Seventy-seven metachronous CTGCTs were diagnosed. The SIR for metachronous CTGCTs was 17.6 (95% confidence interval (95% CI) 13.9-22.0). Standardised incidence ratios remained elevated for up to 20 years, while the 20-year cumulative incidence was 2.2% (95% CI 1.8-2.8%). Platinum-based chemotherapy was associated with a lower CTGCT risk among non-seminoma patients (hazard ratio 0.37, 95% CI 0.18-0.72). The CTGCT patients had a 2.3-fold (95% CI 1.3-4.1) increased risk to develop a subsequent non-TGCT cancer and, consequently, a 1.8-fold (95% CI 1.1-2.9) higher risk of death than patients without a CTGCT., Conclusion: The TGCT patients remain at increased risk of a CTGCT for up to 20 years. Treatment with platinum-based chemotherapy reduces this risk.

Aim: After the publication of several reports that the utilisation rate of radiotherapy for patients with non-small cell lung cancer (NSCLC) varies for both medical and non-medical reasons, the utilisation of radiotherapy was studied in four regions in the Netherlands., Materials and Methods: Data from 1997-2008 were collected from the population-based cancer registries of four comprehensive cancer centres ('regions'), which represent about half of the Dutch population, resulting in 24 185 non-metastatic patients with NSCLC. Treatment had to be started or planned within 6 months of diagnosis. We evaluated the utilisation of radiotherapy according to age, gender and period for each region., Results: The utilisation of radiotherapy alone decreased over time (from 35 to 19%), whereas the utilisation of radiotherapy in combination with chemotherapy increased (from 5 to 19%). The total utilisation rate remained rather stable at about 40%. The differences between the four regions remained in general no more than 15%. Elderly patients with stage I and II disease had increased odds of receiving radiotherapy (≥75 versus <50 years: odds ratio 2.6, 95% confidence interval 2.0-3.3, whereas this was the opposite for patients with stage III disease: odds ratio 0.5, 95% confidence interval 0.4-0.6). For 17-24% of all patients, especially the elderly, best supportive care was applied., Conclusions: In the Netherlands, with good accessibility to medical care and well-implemented national guidelines, variation between the four regions is limited for the treatment of non-metastatic NSCLC with radiotherapy., (Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aims: To describe variation in the utilisation rates of primary radiotherapy for patients with rectal cancer in the Netherlands, focusing on time trends and age effects., Materials and Methods: Data on primary non-metastatic rectal cancer were derived from the population-based cancer registries of four comprehensive cancer centres (regions) in the Netherlands (1997-2008, n=13,055)., Results: An increase in the utilisation rate was noted for the four regions, from 37-46% in 1997 to 66-76% in 2008, for both genders. This increase was found predominately for preoperative radiotherapy (from 13-31% to 58-67%) and (unsurprisingly) was most pronounced for stage T2-3 patients (from 9-27% to 68-80%). The probability of receiving radiotherapy decreased with age: the odds of receiving preoperative radiotherapy was reduced in patients aged 65 years and older, as well as the odds of receiving postoperative radiotherapy in those aged 75 years and older, which remained significant after adjustment for stage, gender and region. Regional differences persisted in multivariable analyses, i.e. the odds of receiving preoperative radiotherapy was reduced in two regions: odds ratio: 0.4 (95% confidence interval: 0.4-0.5) and 0.7 (0.6-0.8). The odds of receiving postoperative radiotherapy was significantly increased in these regions [odds ratio: 2.6 (2.2-3.2) and 1.6 (1.3-1.9), respectively] and reduced in another [odds ratio 0.8 (0.6-0.96)]., Conclusions: The utilisation rate of radiotherapy for rectal cancer increased significantly over time, particularly for preoperative radiotherapy and was most pronounced for T2-3 patients. Due to national multidisciplinary treatment guidelines, regional differences became limited in recent years after adjustment for age and stage of the disease. A low utilisation rate of radiotherapy was seen in women and elderly patients., (Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

The associations of socioeconomic status (SES) and participation in the breast cancer screening program, as well as consequences for stage of disease and prognosis were studied in the Netherlands, where no financial barriers for participating or health care use exist. From 1998 to 2005, 1,067,952 invitations for biennial mammography were sent to women aged 50-75 in the region covered by the Eindhoven Cancer Registry. Screening attendance rates according to SES were calculated. Tumor stage and survival were studied according to SES group for patients diagnosed with breast cancer between 1998 and 2006, whether screen-detected, interval carcinoma or not attended screening at all. Attendance rates were rather high: 79, 85 and 87% in women with low, intermediate and high SES (p < 0.001), respectively. Compared to the low SES group, odds ratios for attendance were 1.5 (95%CI:1.5-1.6) for the intermediate SES group and 1.8 (95%CI:1.7-1.8) for the high SES group. Moreover, women with low SES had an unfavorable tumor-node-metastasis stage compared to those with high SES. This was seen in non-attendees, among women with interval cancers and with screen-detected cancers. Among non-attendees and interval cancers, the socioeconomic survival disparities were largely explained by stage distribution (48 and 35%) and to a lesser degree by therapy (16 and 16%). Comorbidity explained most survival inequalities among screen-detected patients (23%). Despite the absence of financial barriers for participation in the Dutch mass-screening program, socioeconomic inequalities in attendance rates exist, and women with low SES had a significantly worse tumor stage and lower survival rate.

Aim: The purpose was to study variations in utilisation rates of external beam radiotherapy (EBRT) and brachytherapy (BT) for prostate cancer patients., Materials and Methods: We calculated the proportion and number of EBRT and BT given or planned within 6 months of diagnosis in 4 Dutch regions, according to stage and age in a population-based setting including 47,259 prostate cancer patients diagnosed from 1997 until 2008., Results: During this study period, the overall utilisation rate of EBRT remained stable at around 25%, while the rate of BT for non-metastasized patients increased from 1% (95% CI:0-1%) to 12% (11-13%) in 2006 and slightly decreased towards 10% (9-11%) in 2008. From 2001 on, the overall utilisation rate of EBRT decreased significantly in one region (p<0.05). In this region, a sharp rise in the utilisation rate of BT for non-metastatic patients was noted to 17% (14-20%) in 2008 after a peak of 24% (21-27%) in 2006. For localised disease, BT was used more often at the expense of EBRT while for locally advanced disease the utilisation rate of EBRT increased. In the multivariate analysis, regional differences in the utilisation rate of EBRT persisted with odds ratios ranging from 0.7 to 0.9 compared to the reference region. Moreover, low rates of EBRT were associated with high BT rates. The regional differences could not be explained by differences in risk profiles., Conclusions: The utilisation rate of EBRT remained stable with limited variation between regions while BT was used increasingly with clear regional differences. To cope with this and in view of the increasing incidence of prostate cancer, adequate resources have to be planned for the optimal care of these patients., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Comorbidity and socioeconomic status (SES) may be related among cancer patients., Method: Population-based cancer registry study among 72,153 patients diagnosed during 1997-2006., Results: Low SES patients had 50% higher risk of serious comorbidity than those with high SES. Prevalence was increased for each cancer site. Low SES cancer patients had significantly higher risk of also having cardiovascular disease, chronic obstructive pulmonary diseases, diabetes mellitus, cerebrovascular disease, tuberculosis, dementia, and gastrointestinal disease. One-year survival was significantly worse in lowest vs highest SES, partly explained by comorbidity., Conclusion: This illustrates the enormous heterogeneity of cancer patients and stresses the need for optimal treatment of cancer patients with a variety of concomitant chronic conditions.

Background: Since the 1970s there have been few epidemiological studies of scrotal cancer. We report on the descriptive epidemiology of scrotal cancer in the Netherlands., Methods: Data on all scrotal cancer patients were obtained from the Netherlands Cancer Registry (NCR) in the period 1989-2006 and age-standardised incidence rates were calculated also according to histology and stage. Relative survival was calculated and multiple primary tumours were studied., Results: The overall incidence rate varied around 1.5 per 1,000,000 person-years, most frequently being squamous cell carcinoma (27%), basal cell carcinoma (19%) and Bowen's disease (15%). Overall 5-year relative survival was 82%, being 77% and 95% for patients with squamous and basal cell carcinoma, respectively. In all, 18% of the patients were diagnosed with a second primary tumour., Conclusion: The incidence rate of scrotal cancer did not decrease, although this was expected; affected patients might benefit from regular checkups for possible new cancers.

Background: Cancer incidence varies according to socioeconomic status (SES) and time trends. SES category may thus point to differential effects of lifestyle changes but early detection may also affect this., Patients and Methods: We studied patients diagnosed in 1996-2008 and registered in the South Netherlands Cancer registry. Incidence rates and estimated annual percentage changes were calculated according to SES category, age group (25-44, 45-64 and > or =65) and sex., Results: People with a low SES exhibited elevated incidence rates of cancer of the head and neck, upper airways (both sexes), gastro-intestinal tract, squamous cell skin cancer, breast (> or =65) and all female genital, bladder, kidney and mature B-cells (all in females only), whereas prostate cancer, basal cell skin cancer (BCC) and melanoma (both except in older females) were most common among those with a high SES. Due to the greater increase in prostate cancer and melanoma in high SES males and the larger reduction of lung cancer in low SES males, incidence of all cancers combined became more elevated among males of > or =45 years with a high and intermediate SES, and approached rates for low SES men aged 45-64. In spite of more marked increases in the incidence of colon, rectal and lung cancer in high SES women, the incidence of all cancers combined remained highest for low SES women of > or =45 years. However, at age 25-44 years, the highest incidence of cancer of the breast and melanoma was observed among high SES females. During 1996-2008 inequalities increased unfavourably among higher SES people for prostate cancer, BCC (except in older women) and melanoma (at middle age), while decreasing favourably among low SES people for cancers of the oesophagus, stomach, pancreas and kidney (both in females only), breast (> or =65 years), corpus uteri and ovary., Conclusions: Although those with a low SES exhibited the highest incidence rates of the most common cancers, higher risks were observed among those with high SES for melanoma and BCC (both except older females) and for prostate and breast (young females) cancer. Altogether this might also have contributed to the recent higher cancer awareness in Dutch society which is usually promoted more by patients of high SES and those who know or surround them., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Development of both basal cell carcinoma (BCC) and cutaneous malignant melanoma (MM) is associated with acute and intermittent sun exposure. In contrast to MM, the association between socioeconomic status (SES) and BCC is not well documented., Objectives: To investigate the incidence of BCC according to SES, stratifying by age and tumour localization in a large population-based cohort. To assess changes over time in the distribution of the patients with BCC across the SES categories., Methods: All patients with a histologically confirmed first primary BCC (n = 27,027) diagnosed between 1988 and 2005 in the Southeast of The Netherlands were stratified by sex, age (25-44, 45-64 and > or = 65 years), period of diagnosis, SES category (based on income and value of housing) and localization of the BCC. Age-standardized BCC incidence rates were calculated for the year 2004 by SES category and localization. Ordinal regression was used to assess changes over time in the proportion of patients with BCC by sex, age and SES., Results: For men in all age groups higher BCC incidence in the highest SES category was observed, which remained significant after stratification for tumour localization. For women a consistent relationship was found only in younger women (< 65 years) for truncal BCCs, which occurred more frequently in high SES groups. Between 1990 and 2004, the proportion of BCC patients with high SES increased (+6%) and the proportion with low SES decreased (-7%)., Conclusions: High SES is associated with increased incidence of BCC among men. Our data suggest that BCC is changing from a disease of the poor to a disease of the rich.

The purpose of this study was to examine trends in incidence and detection of ductal carcinoma in situ (DCIS) of the breast in southern Netherlands in the period 1984-2006 and assess the effect of mass screening. All patients with primary DCIS registered between 1984 and 2006 in the population-based Eindhoven Cancer Registry were included (n = 1,767). These data were linked to data from the population-based screening programme. The incidence of DCIS of the breast increased from 3/100,000 to almost 34/100,000 person-years in women aged 50-69 years in southern Netherlands since 1984. Mass screening was responsible for this increase. A stable 60% of DCIS was screen-detected. Over 11% of breast cancer patients have DCIS. In conclusion, the incidence of DCIS increased markedly in southern Netherlands with a clear effect of mammography screening since 1992.

The number of female cancer survivors has been rising rapidly. We assessed the occurrence of breast cancer in these survivors over time. We computed incidence of primary breast cancer in two cohorts of female cancer survivors with a first diagnosis of cancer at ages 30+ in the periods 1975-1979 and 1990-1994. Cohorts were followed for 10 years through a population-based cancer registry. Over a period of 15 years, the incidence rate of breast cancer among female cancer survivors increased by 30% (age-standardised rate ratio (RR-adj): 1.30; 95% CI: 1.03-1.68). The increase was significant for non-breast cancer survivors (RR-adj: 1.41, 95% CI: 1.04-2.75). During the study period, the rate of second breast cancer stage II tripled (RR-adj: 3.10, 95% CI: 1.73-5.78). Non-breast cancer survivors had a significantly (P value=0.005) more unfavourable stage distribution (62% stage II and III) than breast cancer survivors (32% stage II and III). A marked rise in breast cancer incidence among female cancer survivors was observed. Research to optimise follow-up strategies for these women to detect breast cancer at an early stage is warranted.

Background: The impact of age and adjuvant therapy on contralateral breast cancer (CBC) risk and prognostic significance of CBC were evaluated., Patients and Methods: In 45,229 surgically treated stage I-IIIA patients diagnosed in the Netherlands between 1989 and 2002 CBC risk was quantified using standardised incidence ratios (SIRs), cumulative incidence and Cox regression analysis, adjusted for competing risks., Results: Median follow-up was 5.8 years, in which 624 CBC occurred <6 months after the index cancer (synchronous) and 1,477 thereafter (metachronous). Older age and lobular histology were associated with increased synchronous CBC risk. Standardised incidence ratio (SIR) of CBC was 2.5 (95% confidence interval (95% CI) 2.4-2.7). The SIR of metachronous CBC decreased with index cancer age, from 11.4 (95% CI 8.6-14.8) when <35 to 1.5 (95% CI 1.4-1.7) for > or =60 years. The absolute excess risk of metachronous CBC was 26.8/10,000 person-years. The cumulative incidence increased with 0.4% per year, reaching 5.9% after 15 years. Adjuvant hormonal (Hazard rate ratio (HR) 0.58; 95% CI 0.48-0.69) and chemotherapy (HR 0.73; 95% CI 0.60-0.90) were associated with a markedly decreased CBC risk. A metachronous CBC worsened survival (HR 1.44; 95% CI 1.33-1.56)., Conclusion: Young breast cancer patients experience high synchronous and metachronous CBC risk. Adjuvant hormonal or chemotherapy considerably reduced the risk of CBC. CBC occurrence adversely affects prognosis, emphasizing the necessity of long-term surveillance directed at early CBC-detection.

Background: Much progress has been made in the early diagnosis and treatment of breast cancer. We have assessed the changing burden of this disease, by means of a comprehensive description of trends in incidence, survival, and mortality., Methods: Data on breast cancer patients diagnosed between 1975 and 2004 (n = 26,464) registered in the population-based Eindhoven Cancer Registry were investigated., Results: Incidence for patients aged below 40 and 40-49 has increased by 2.1% and 2.4% annually, since 1995 (p = 0.08 and p = 0.001, respectively). Mortality decreased in all age groups, but most markedly among women aged 50-69 (-1.5% yearly since 1985, p = 0.14). The proportion of stage I tumors increased from 25% to 39%, that of advanced stages (III & IV) decreased from 30% (1975-1984) to 13% in 1995-2004, and the proportion of in situ tumors increased from 1.5% to 10%. Adjuvant systemic treatment was administered to 15% of patients in 1975-1984 vs. 49% in 1995-2004. Relative 10-year survival rates for women aged 50-69 (period analysis) increased from 53% to 75% between 1975 and 2004. The best prognosis was observed for women aged 45-54. Women younger than 35 had a particularly poor prognosis., Conclusion: The observed improvement in survival of breast cancer patients during the last three decades is impressive. The peak in breast cancer incidence is not yet in sight considering the recent trends in exposure to known risk factors and improved diagnosis. The combination of increasing incidence and improved survival rates implies that the number of prevalent cases will continue to increase considerably in the next 10 years.

Background: After a systematic mass mammography breast cancer screening programme was implemented between 1991 and 1996 (attendance 80%), we evaluated its impact on survival according to socioeconomic status (SES)., Methods: We studied survival rates up to 1-1-2005 for all consecutive breast cancer patients aged 50-69 and diagnosed in the period 1983-2002 in the area of the Eindhoven Cancer Registry (n = 4939). Multivariate analyses were performed using Cox regression analysis., Results: The proportion of breast cancer patients with a low SES decreased from 22% in 1983-1990 to 14% in 1997-2002 when attendance was 85%. The proportion of newly diagnosed patients with stage III or IV disease in 1997-2002 was only 10% compared to 14% in 1991-1996 and 26% in 1983-1989 (P < 0.0001). Stage distribution improved for all socio-economic groups (P = 0.01). Survival was similar for all socio-economic groups in 1983-1990, but after the introduction of the screening programme women with low SES had lower age- and stage-adjusted survival rates (HR 2.0, 95%CI: 1.3-3.0). Survival was better for patients diagnosed in 1997-2002 compared to 1983-1990 for all socioeconomic strata; it was substantially better for the high SES group (HR 0.36, 0.2-0.5) compared to the lowest SES (HR 0.77, 0.6-1.1)., Conclusion: Although survival improved for women from each of the socio-economic strata, related to the high participation rate of the screening programme, women from lower socio-economic strata clearly benefited less from the breast cancer screening programme. That is also related to the higher prevalence of comorbidity and possibly suboptimal treatment.

Breast cancer will increasingly become a disease affecting the lives of older women, especially in more developed countries, the prevalence rising up to 7% over age 70 in the near future. A review of the population-based literature and an analysis of the data of the Eindhoven Cancer Registry and European data regarding the diagnosis, treatment and prognosis showed that the proportion with unstaged and advanced disease (stages III and IV) is higher among elderly patients compared to younger ones and that their treatment is generally less aggressive, although the proportion receiving chemotherapy is increasing since the early 1990s. Disease specific (or relative) survival of elderly breast cancer patients is generally lower and the prevalence of serious (life expectancy affecting) co-morbidity is higher (>50% in patients over age 70). Because of large individual variations in physical and mental conditions, limited evidence from RCTs and personal preferences prevailing in the decision-making process, treatment of older breast cancer patients seems difficult to fit into guidelines. Therefore, alternative research strategies are needed to understand and improve the care for the elderly breast cancer population, such as descriptive (registry-based) studies and a qualitative, individual-based approach.

Aims: To study, in a population-based setting, the use of delayed radiotherapy (RT) in a cohort of 2008 unselected rectal cancer patients diagnosed between 1996 and 2000., Patients and Methods: Radiation within 6 months of diagnosis was considered part of the primary treatment (PRT). RT given 6 months or later after diagnosis or after PRT was considered as delayed or secondary RT (SRT). Number, percentage and cumulative proportion of patients receiving SRT were calculated. The odds for receiving SRT (total and for recurrent rectal cancer only) were studied by logistic regression analysis, taking into account age, gender, co-morbidity, socio-economic status, stage, prior PRT and RT department (2 departments, each serving general hospitals only)., Results: Forty-six percent of all newly diagnosed patients received RT. Ten percent (n=203) received at least once SRT, either after PRT or as first RT, of which 96 patients for a relapsed rectal tumour (31 after PRT on the rectal tumour, 65 as a first radiation treatment). In a multivariate analysis of patients with rectal recurrence secondary pelvic irradiation was less often given after primary irradiation (OR: 0.7, 95% CI: 0.4-1.1). Patients with a stage III significantly more often received SRT on a recurrence (OR=2.5, 95% CI=1.4-4.5). Generally, patients in the eastern department received more often PRT and less often SRT for recurrence (OR: 0.5, 95% CI: 0.3-0.8)., Conclusions: Five percent of all patients with rectal cancer received SRT on a recurrent tumour, with a large variation between the two RT departments in the region.

We studied the use of radiotherapy (RT) (especially secondary RT) in a cohort of 6561 patients in southern Netherlands with invasive breast cancer diagnosed between 1996 and 2000 (median follow-up: 66 months, range 0-107 months). Radiation within 6 months of diagnosis was considered primary RT (PRT). RT given 6 months or later after diagnosis or after PRT was considered secondary RT (SRT). Of all patients, 67% received RT, 3554 only PRT, 323 only SRT and 503 both. The cumulative use of SRT at 100 months was 17%. The 826 patients receiving SRT underwent 1846 courses 0-105 months (median 36) after diagnosis; the retreat rate was 35%. Elderly patients received SRT significantly less often (OR(age50-69)=0.7, 95%CI=0.6-0.8, OR(age> or 70)=0.4, 95%CI=0.3-0.5). The following factors increased the chance for SRT: patients from the eastern region (OR=1.3, 95%CI=1.1-1.6); patients who received PRT (OR=1.3, 95%CI=1.0-1.5) and patients who underwent mastectomy including axillary node dissection as well as unresected patients (OR=1.9, 95%CI=1.5-2.4, OR=2.6, 95%CI=1.7-3.9, respectively). Thirteen percent of all patients with breast cancer received SRT, with a large variation in age and between the 2 RT departments in the region.

Among 1276 primary breast carcinoma in situ (BCIS) patients diagnosed in 1972-2002 in the Southern Netherlands, 11% developed a second cancer. Breast carcinoma in situ patients exhibited a two-fold increased risk of second cancer (standardised incidence ratios (SIR): 2.1, 95% confidence interval (CI): 1.7-2.5). The risk was highest for a second breast cancer (SIR: 3.4, 95% CI: 2.6-4.3; AER: 66 patients per 10,000 per year) followed by skin cancer (SIR: 1.7, 95% CI: 1.1-2.6; AER: 17 patients per 10,000 per year). The increased risk of second breast cancer was similar for the ipsilateral (SIR: 1.9, 95% CI: 1.3-2.7) and contralateral (SIR: 2.0, 95% CI: 1.4-2.8) breast. Risk of second cancer was independent of age at diagnosis, type of initial therapy, histologic type of BCIS and period of diagnosis. Standardised incidence ratios of second cancer after BCIS (SIR: 2.3, 95% CI: 1.8-2.8) resembled that after invasive breast cancer (SIR: 2.2, 95% CI: 2.1-2.4). Surveillance should be directed towards second (ipsi- and contra-lateral) breast cancer.

Node-negative breast cancer patients have a relatively good prognosis, but eventually one-third will die of the disease. Thus, prognostic factors to identify the high-risk group among these patients are needed. We retrospectively determined the Mitotic Activity Index (MAI) for a large series of node-negative breast cancer patients (n = 468) with tumours smaller than 5 cm, who only received locoregional treatment. Patients were followed for up to 29 years; crude and relative survival were calculated, both univariate and multivariate. Relative survival differed significantly according to MAI (p = 0.05), the difference occurred in the first 5 years after diagnosis and remained constant thereafter. After adjustment, MAI still significantly affected relative survival (RER, 1.9; 95% CI, 1.1-3.5). Tumour size also increased the risk, but this was not statistically significant (RER, 1.5; 95% CI, 0.8-2.7). Survival of patients with a T1 tumour and MAI < 10 was similar to that for the general population in the first 5 years after diagnosis. In conclusion, MAI significantly predicted long-term survival for T1/T2N0 breast cancer. Adjuvant systemic therapy appears to have little benefit for node-negative breast cancer patients with a T1 tumour, regardless of the MAI. For those with a T2 tumour and a MAI > or = 10 systemic therapy might have reduced mortality. The need for close surveillance of node-negative breast cancer patients with a T1 tumour and MAI < 10 seems limited., (2005 Wiley-Liss, Inc.)

In this study, we have assessed whether referral for primary radiotherapy varied according to hospital size in a region with 1 million inhabitants served by community hospitals. We studied 20178 patients diagnosed with breast, non-small cell lung, prostate, rectal, or endometrial cancer between 1988 and 1999. We used logistic regression analysis, adjusted for age, stage and period of diagnosis. Medium-sized and small hospitals referred breast cancer patients more often (OR=2.2, 95%CI: 2.0-2.5, OR=1.2, 95%CI: 1.1-1.4, respectively), and patients with prostate cancer less often (OR=0.7 (0.5-0.8) and 0.7 (0.6-0.9), respectively). Referral rates for patients with non-small cell lung and rectal cancer showed minor differences according to hospital size, referral for endometrial cancer was somewhat higher for patients from medium-sized hospitals (OR=1.5 (1.0-2.1)). Time trends in variation were shown, but differences according to hospital size only decreased over time for rectal cancer. Despite multidisciplinary oncology meetings and treatment guidelines there were large variations in rates of referral for radiotherapy.

A cohort of 9919 breast cancer patients from the population-based Eindhoven Cancer Registry was followed for vital status and development of second cancer. Person-year analysis was applied to determine the risk of second primary breast or urogenital cancer among breast cancer patients and to assess its correlation with age, treatment and time since the first breast cancer diagnosis. Women with previous breast cancer have an elevated risk of overall second breast or urogenital cancer. The largest relative risk was observed for second breast cancer (SIR (standardised incidence ratio) 3.5; 95% confidence interval (CI) 3.2-3.8) and second ovarian cancer (SIR 1.7; 95% CI 1.2-2.3). The absolute excess risk was highest for second breast cancer (64/10,000 patients/year). However, breast cancer has an inverse relationship to risk of cervical cancer. Changes in behavioural risk factors are important for lowering the risk of second cancer after breast cancer.

Objectives: To assess the risk of second primary cancers among women with previous breast cancer and calculate the excess burden of second cancer in the population., Methods: A population-based longitudinal study was conducted using the Eindhoven cancer registry data on 9919 breast cancer patients diagnosed in the period 1972-2000 and followed until 2001. Standardised incidence ratios (SIR) and absolute excess risks (AER) were calculated., Results: In total, 1298 (13%) women developed a second primary cancer. The risk of overall second cancer was higher among breast cancer patients compared to the general population (SIR: 2.8; 95% CI: 2.6-2.9), with an AER of 115 second cancers for every 10,000 breast cancer patients per year. High SIR and AER were observed for breast cancer (SIR: 4.1; 95% CI: 3.8-4.4; AER: 64/10,000 patients/year) and ovarian cancer (SIR: 2.0; 95% CI: 1.5-2.7; AER: 4.5/10,000 patients/year)., Conclusions: Our recent data show that women with previous breast cancer have an elevated risk of developing a second cancer compared to the general population. Excess burden for the population is especially high for second cancers of the breast, ovary and colon. Screening may only be justified for breast, ovary and colon cancer in certain groups of patients.

The proportion of elderly cancer patients has increased considerably. This means that more patients are being diagnosed with one or more serious concomitant condition which may complicate the treatment of cancer. Little is known about treatment outcomes, as elderly patients with comorbidity are often excluded from clinical trials. The Eindhoven Cancer Registry has been registering serious co-morbidity in North-Brabant and North-Limburg in the Netherlands since 1993. Using data from patients diagnosed with cancer in 1995-2001, the correlation between age and comorbidity and choice of therapy and survival rates was described. Very elderly patients or patients with co-morbidity often were not treated in accordance with the guidelines. Elderly patients with localized lung cancer or prostate cancer underwent less surgery as often and elderly patients with colorectal cancer, breast cancer or ovarian cancer received less adjuvant chemotherapy or radiotherapy than younger patients. The prognosis was often worse for elderly patients than for younger patients, and the presence of co-morbidity decreased survival in most types of tumour. The question remains whether the prognosis for elderly patients with cancer would improve if more of them were treated in accordance with the guidelines, or if this will only lead to more complications.

Background: Skin cancer is an important, growing public health problem among white caucasians, causing a heavy burden on dermatologists and general practitioners., Objectives: To predict the future incidence of skin cancer in the Netherlands up to 2015., Methods: Expected numbers of skin cancer cases in the Netherlands up to 2015 were calculated by trend modelling of observed rates for melanoma and squamous cell carcinoma (SCC) between 1989 and 2000 obtained from the Netherlands Cancer Registry and for basal cell carcinoma (BCC) obtained from the Eindhoven Cancer Registry; these rates were then multiplied by the predicted age distributions. Incidence rates were fitted to four different models, and predictions were based on the best fitting model., Results: An increase of 80% in the total number of skin cancer patients is expected in the Netherlands: from 20 654 in 2000 to 37 342 in 2015. The total number of melanoma cases is expected to increase by 99%, with the largest increase for males (males aged 35-64, 111%; males aged > or = 65, 139%). Numbers of patients with SCC will increase overall by 80%, mainly among older males and females (increase of 79%) and females aged 35-64 (increase of 93%). The number of cases of BCC will increase by 78%, with the largest increase for the combined groups, those aged 15-64 (males, 66% increase; females, 94% increase), especially for sites other than the head and neck. The contribution of demographic changes (ageing effect) was largest for males with BCC and SCC (35-44%)., Conclusions: If incidence rates for skin cancers in the Netherlands continue to increase and population growth and ageing remain unabated, a rise in annual demand for care of more than 5% could occur, putting a heavy burden on general practitioners and dermatologists. In the absence of marked changes in current ultraviolet radiation exposure, these increases will probably continue after 2015.

The prevalence of coexistent diseases in addition to breast cancer becomes increasingly important in an ageing population. However, the clinical implications are unclear. The age-specific prevalence of serious comorbidity among all new breast cancer patients diagnosed from 1995 to 2001 (n=8966) in the South of the Netherlands was analysed in relation to age, stage and treatment. Independent prognostic effects of age and comorbidity were evaluated (follow-up was continued until 1 January 2004). The prevalence of comorbidity increased from 9% for those aged <50 years to 56% for patients aged 80+ years. The most frequent conditions were cardiovascular disease (7%), diabetes mellitus (7%), and previous cancer (6%). In the presence of comorbidity, fewer patients received radiotherapy (51% vs. 66%, P<0.0001) and fewer patients who underwent breast-conserving surgery also had axillary dissection (P<0.0001). Relative 5-year survival rates for patients without comorbidity (87%) were significantly higher (P<0.01) than those for patients with previous cancer (77%), diabetes mellitus (78%), and for patients with 2+ coexistent diseases (59%). Relative survival of patients without comorbidity increased with age to 93% for patients older than 70 years. Comorbidity negatively affected prognosis, independent of age, stage of disease, and treatment (Hazard Ratio (HR)=1.3, P=0.0001 for one coexistent disease and HR=1.4, P=0.0001 for 2+ coexistent diseases). The most important effects were found for previous cancer (HR=1.4, P=0.003), cerebrovascular disease (HR=1.6, P<0.004) or dementia (HR=2.3, P<0.0001). Elderly breast cancer patients can be divided in those without other diseases, who have a relatively good prognosis, and those who have at least one other serious coexistent disease and significantly poorer prognosis.

Background: Little is known about the aetiology of glioma. Research is often hampered by the low incidence and high mortality of the disease. Concomitant diseases in glioma patients may indicate possible aetiological pathways. We therefore studied comorbidity in glioma patients., Patients and Methods: We performed a case-control study using population-based data from the Eindhoven Cancer Registry. We compared prevalences of concomitant diseases in 510 glioma patients with two reference cancer populations from the same registry., Results: Compared with all other cancer patients, a significantly higher prevalence of hypertension was found in glioma patients for age categories 60-74 years [odds ratio (OR) 1.37; 95% confidence interval (CI) 1.02-1.84] and 75+ years (OR 2.37; 95% CI 1.34-4.21). The association was most pronounced in elderly men and in astrocytic glioma, with a maximum in age category 75+ years (OR 5.86; 95% CI 2.20-15.7). The prevalence of cerebrovascular disease was higher in glioma patients >45 years old (OR 1.67; 95% CI 1.12-2.47), whereas the prevalence of other cancers was lower (OR 0.64; 95% CI 0.48-0.87). No consistent associations were detected for several other concomitant diseases., Conclusions: Our data suggest an association between hypertension and glioma, although questions remain about causality and the possible mechanisms. We hypothesise that this association is mediated through potentially neurocarcinogenic effects of antihypertensive medication., (Copyright 2004 European Society for Medical Oncology)

Cancer morbidity and mortality vary among socio-economic groups. We investigated whether educational differences in behaviour could explain the variation in cancer incidence. In 1991, a postal questionnaire on socio-economic status, exposure variables, health and health-related behaviour was filled out by 18,973 participants (response rate 70.1%) of the longitudinal GLOBE study. Participants were followed and linked with the regional population-based Eindhoven Cancer Registry. Between 1991 and 1998 a total of 760 new tumours were found. The risk of cancer (all sites combined) was higher in the three quartiles of lower educational level compared with the highest educational level, odds ratios (ORs) varying from 1.25, 1.34, 1.27 to 1.00 from the lowest to the highest category, respectively (P=0.14). The relative risk (RR) for lung cancer for low versus high education was 2.7 [95% confidence interval (CI) 1.3-5.3]; adjustment for smoking, alcohol intake and physical activity decreased the risk to 1.6 (95% CI 0.8-3.3). Smoking alone explained 39% of the association, when alcohol intake and physical exercise were added to the model 61% of the effect was explained. In conclusion, a lower education is associated with increased cancer risks, which can be explained partly by behavioural factors.

Background: Depression has been hypothesized to be potentially linked to an increased risk of breast cancer. Few studies have addressed this question using population-based cohorts and prospective designs, adjusting for known biomedical risk factors. This has been done in the present investigation., Method: Participants were 5191 women from a cohort of women born between 1941 and 1947 and living in the city of Eindhoven, The Netherlands. All women completed questionnaires regarding the presence of depressive symptoms (Edinburgh Depression Scale) and background (demographic, medical and lifestyle) variables. The questionnaire data were linked with the records of the Eindhoven Cancer Registry. These records provided data on breast cancer diagnoses, which took place up to 5 years after the questionnaire screening., Results: Fifty-eight women (1.1%) were found to have developed breast cancer at least 2 years after the questionnaire screening. After controlling for 15 potential risk factors, of which family history of breast cancer, hypothyroidism and unilateral oophorectomy were significant predictors of breast cancer development, women with depressive symptoms had a lower risk of subsequent breast cancer (OR=0.29, 95% CI=0.09-0.92, P=0.04)., Conclusions: Depressive complaints may be associated with a protective factor involved in the development of breast cancer. Some of the possible candidates for this factor are discussed.

Objective: To describe the changes in incidence, mortality, survival and prevalence of cancer since 1970 in the south-eastern part of the Netherlands, the registration area of the Eindhoven Cancer Registry., Design: Descriptive population-based study., Method: Data were collected on all patients diagnosed with cancer between 1970 and 1999 in the south-eastern part of the Netherlands, the registration area of the Eindhoven Cancer Registry. Trends in age-specific and age-adjusted incidence, mortality, prevalence and relative survival were calculated. The changes in incidence were compared with changes in exposure to risk factors, such as smoking, alcohol, diet, infections and sunlight, and with early detection., Results: The incidence of cancer of the stomach and uterine cervix decreased in the study period. Among men, the incidence of lung cancer increased sharply until the mid 1980s, whereafter it decreased. Furthermore, the incidence of cancer of the oesophagus, colon, rectum, breast, prostate and lung (in women), cutaneous melanoma and non-Hodgkin's lymphoma also increased. The survival improved for patients with cancer of the rectum, breast, female genital tract, prostate, testis (non-seminoma), cutaneous melanoma and Hodgkin's disease. The improvement in survival could be explained in part by early detection and partly by the improvement in treatment strategies. The prevalence of the diagnosis 'cancer' in living subjects increased by almost 30%, which may be related to the increase in incidence and the improvement in survival., Conclusion: There was an alarming increase in tumours related to exposure to tobacco and alcohol, especially in women. Improved diagnostic techniques and treatment strategies coincided with improved prognosis. This was associated with an increased demand for health care.

Objective: The increased incidence of breast cancer in the southeastern Netherlands was accompanied by markedly improved relative survival and stable mortality. We investigated whether the average aggressiveness of tumors changed over time in a population-based study, before the introduction of mass screening., Methods: The mitotic activity index (MAI) was determined retrospectively for 1051 consecutive patients diagnosed with invasive, non-metastatic breast cancer in 1975, 1981, 1988, and 1989. Trends over time, and effects of age, tumor size and lymph node status were examined by univariate and multivariate regressions., Results: Age-adjusted incidence of low MAI tumors changed from 35/100,000 in 1975 to 45/100,000 in 1988-89, an increase of 30% (P = 0.01), the incidence of tumors with a high MAI increased about 20% (P = 0.28), from 25 to 29/100,000. For small tumors (T1) the odds for a high MAI was lower in 1981 (OR: 0.80; 95% CI: 0.37-1.73) and 1988-89 (OR: 0.66; 95% CI: 0.35-1.23) compared to 1975. Among T3 and T4 tumors the odds increased to 2.03 (95% Cl: 0.71-5.86) in 1981 and 2.16 (0.76-6.18) in 1988-89., Conclusion: Although the incidence of tumors with low aggressive potential increased, the incidence of high MAI tumors also increased. Stable breast cancer mortality rates in the face of increasing incidence rates during the period 1975-89 cannot be attributed solely to changes in tumor aggressiveness; early diagnosis and better treatment may also have contributed.

In a population-based study, causes of death were traced of 418 deceased breast cancer patients diagnosed in 1960-1979 who survived at least 10 years after diagnosis. The pattern of causes of death in these patients was compared with the general female population using standardized mortality ratios (SMRs). Of 418 patients surviving at least 10 years, 196 (47%) died from breast cancer and 50 (12%) died from another cancer. The SMR for breast cancer was 15.8 (95% CI: 13.1-18.8) 10-14 years after diagnosis; it was still 4.7 (95% CI: 2.6-7.8) after 20 years. Overall mortality was higher than expected 10-14 years after diagnosis (SMR: 1.3; 95% CI: 1.1-1.5), but lower after more than 20 years (SMR: 0.6; 95% CI: 0.4-0.7). Despite a normal (or even improved) life expectancy for breast cancer patients 20 years after diagnosis the risk of dying from this disease remained elevated., (Copyright 2001 Cancer Research Campaign.)

Recently, the Dutch Society for Medical Oncology published new consensus guidelines for the use of adjuvant systemic treatment in patients with operable breast cancer. We used data of the cancer registry of the Comprehensive Cancer Centre South to predict the change in the number of patients who will be candidates for systemic treatment according to these new guidelines. It was estimated that of all patients with operable breast cancer, 15% should receive chemotherapy, 27% hormonal therapy and 17% a combination of both modalities. Of the patients with negative axillary lymph nodes, one-third will receive adjuvant systemic treatment. Compared with the previous guidelines, the introduction of the new guidelines will cause a 50% increase in the number of patients receiving adjuvant systemic treatment in Dutch hospitals.