Treatment of melanoma of unknown primary in the era of immunotherapy and targeted therapy: A Dutch population-based study.

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.

Trends in breast biopsies for abnormalities detected at screening mammography: a population-based study in the Netherlands.

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.

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.

Risk and prognostic significance of metachronous contralateral testicular germ cell tumours.

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.

Socioeconomic inequalities in attending the mass screening for breast cancer in the south of the Netherlands--associations with stage at diagnosis and survival.

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.

Survival of sentinel node biopsy versus observation in intermediate-thickness melanoma: A Dutch population-based study.

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.

Scrotal cancer: incidence, survival and second primary tumours in the Netherlands since 1989.

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.

A 50% higher prevalence of life-shortening chronic conditions among cancer patients with low socioeconomic status.

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.

Rising incidence of breast cancer among female cancer survivors: implications for surveillance.

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.

Screening caused rising incidence rates of ductal carcinoma in situ of the breast.

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.

Increase in basal cell carcinoma incidence steepest in individuals with high socioeconomic status: results of a cancer registry study in The Netherlands.

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.

Are patients with skin cancer at lower risk of developing colorectal or breast cancer?

Ultraviolet exposure may reduce the risk of colorectal and breast cancer as the result of rising vitamin D levels. Because skin cancer is positively related to sun exposure, the authors hypothesized a lower incidence of breast and colorectal cancer after skin cancer diagnosis. They analyzed the incidence of colorectal and breast cancer diagnosed from 1972 to 2002 among 26,916 Netherlands skin cancer patients (4,089 squamous cell carcinoma (SCC), 19,319 basal cell carcinoma (BCC), and 3,508 cutaneous malignant melanoma (CMM)). Standardized incidence ratios were calculated. A markedly decreased risk of colorectal cancer was found for subgroups supposedly associated with the highest accumulated sun exposure: men (standardized incidence ratio (SIR) = 0.83, 95% confidence interval (CI): 0.71, 0.97); patients with SCC (SIR = 0.64, 95% CI: 0.43, 0.93); older patients at SCC diagnosis (SIR = 0.59, 95% CI: 0.37, 0.88); and patients with a SCC or BCC lesion on the head and neck area (SIR = 0.59, 95% CI: 0.36, 0.92 for SCC and SIR = 0.78, 95% CI: 0.63, 0.97 for BCC). Patients with CMM exhibited an increased risk of breast cancer, especially advanced breast cancer (SIR = 2.20, 95% CI: 1.10, 3.94) and older patients at CMM diagnosis (SIR = 1.87, 95% CI: 1.14, 2.89). Study results suggest a beneficial effect of continuous sun exposure against colorectal cancer. The higher risk of breast cancer among CMM patients may be related to socioeconomic class, both being more common in the affluent group.

Improved stratification of pT1 melanoma according to the 8th American Joint Committee on Cancer staging edition criteria: A Dutch population-based study.

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.

Clinical epidemiology of breast cancer in the elderly.

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.

A population based study of radiotherapy in a cohort of patients with breast cancer diagnosed between 1996 and 2000.

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.

A population-based study of radiotherapy in a cohort of patients with rectal cancer diagnosed between 1996 and 2000.

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.

Practice variation in Sentinel Lymph Node Biopsy for melanoma patients in different geographical regions in the Netherlands.

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.

Hospital variation in referral for primary radiotherapy in South Netherlands, 1988-1999.

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.

Less extensive treatment and inferior prognosis for breast cancer patient with comorbidity: a population-based study.

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.

Risks of second primary breast and urogenital cancer following female breast cancer in the south of The Netherlands, 1972-2001.

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.