PURPOSE: Cardiovascular disease (CVD) is a potential adverse effect of endocrine treatment (ET) for prostate cancer (PC). We investigated absolute and relative CVD risk in 76,600 patients with PC undergoing ET, curative treatment, or surveillance. METHODS: PCBaSe Sweden is based on the National Prostate Cancer Register, which covers more than 96% of PC cases. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) of ischemic heart disease (IHD), acute myocardial infarction (MI), arrhythmia, heart failure, and stroke were calculated to compare observed and expected (using total Swedish population) numbers of CVD, taking into account age, calendar time, and previous CVD. RESULTS: Between 1997 and 2007, 30,642 patients with PC received primary ET, 26,432 curative treatment, and 19,527 surveillance. SIRs for CVD were elevated in all men with the highest for those undergoing ET, independent of circulatory disease history (SIR MI for men without circulatory disease history: 1.40 [95% CI, 1.31 to 1.49], 1.15 [95% CI, 1.01 to 1.31], and 1.20 [95% CI, 1.11 to 1.30] for men undergoing ET, curative treatment, and surveillance, respectively). Absolute risk differences (ARD) showed that two (arrhythmia) to eight (IHD) extra cases of CVD would occur per 1,000 person-years. SMRs showed similar patterns, with ARD of zero (arrhythmia) to three (IHD) per 1,000 person-years. CONCLUSION: Increased relative risks of nonfatal and fatal CVD were found among all men with PC, especially those treated with ET. Because ET is currently the only effective treatment for metastatic disease and the ARDs were rather small, our findings indicate that CVD risk should be considered when prescribing ET but should not constitute a contraindication when the expected gain is tangible.
Adherence to long-term pharmacological treatment for chronic conditions is often less than optimal. Till date, a limited number of population-based studies have assessed adherence to adjuvant hormonal therapy in breast cancer, a therapy with proven benefits in terms of reductions of recurrence and mortality. We aimed to examine rates of adherence and early discontinuation in Sweden where prescribed medications are subsidized for all residents and made available at reduced out-of-pocket costs. Individual-level data were obtained from Regional Clinical Quality Breast Cancer Registers, the Swedish Prescribed Drug Register, and several other population-based registers. Multivariate logistic regression was used to analyze factors associated with adherence to prescribed medication for a period of 3 years. Between January 1 and December 31, 2005, 1,741 patients in central Sweden were identified with estrogen receptor positive breast cancer, and at least one prescription dispensation of either tamoxifen or an aromatase inhibitor. Of these women, 1,193 (69%) were fully adherent to therapy for 3 years (medication possession ratio of 80% or higher and a maximum of 180 days between refills). During the 3-year follow-up, 215 women (12%) had prematurely discontinued therapy. Adherence was positively associated with younger age, large tumor size, being married, and being born in the Nordic countries, while no clear association was observed with education or income. During the 3 years of follow-up, 31% of women were non-adherent to therapy. Further efforts must be undertaken to promote adherence over the entire recommended treatment period.
Treatment of metastatic breast cancer (MBC) has evolved during the last decades but it is largely unknown whether this has led to improved survival in the general MBC population. Based on the regional, population-based breast cancer registry, we identified 5,463 patients diagnosed with MBC in Stockholm County during 1979-2004. Patients were divided into five cohorts based on the year of first MBC diagnosis and observed and relative survival were compared across the cohorts after adjustment for potential confounders. A significant trend of better survival over time was demonstrated for patients 60 years or younger (P
Our purpose was to investigate whether alcohol (ethanol) consumption could have an influence on the metabolism of acrylamide to glycidamide in humans exposed to acrylamide through food. We studied a subsample from a population-based case-control study of prostate cancer in Sweden (CAPS). Questionnaire data for alcohol intake estimates was compared to the ratio of hemoglobin-adduct levels for acrylamide and glycidamide, used as a measure of individual differences in metabolism. Data from 161 non-smoking men were processed with regard to the influence of alcohol on the metabolism of acrylamide to glycidamide. A negative, linear trend of glycidamide-adduct to acrylamide-adduct-level ratios with increasing alcohol intake was observed and the strongest association (p-value for trend=0.02) was obtained in the group of men with the lowest adduct levels (47 pmol/g globin) when alcohol intake was stratified by acrylamide-adduct levels. The observed trend is likely due to a competitive effect between ethanol and acrylamide as both are substrates for cytochrome P450 2E1. Our results, strongly indicating that ethanol influence metabolism of acrylamide to glycidamide, partly explain earlier observations of only low to moderate associations between questionnaire data on dietary acrylamide intake and hemoglobin-adduct levels.
Androgen Deprivation Therapies and Changes in Comorbidity: A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer.
Australian Centre for Precision Health, University of South Australia, Adelaide, Australia; Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, UK. Electronic address: Kerri.firstname.lastname@example.org.
Some studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias.
To investigate rates of change in comorbidity for men on GnRH agonists versus AA monotherapy in a population-based register study.
Men with advanced nonmetastatic prostate cancer (PCa) who received primary AA (n=2078) or GnRH agonists (n=4878) and age- and area-matched PCa-free men were selected from Prostate Cancer Database Sweden 3.0. Increases in comorbidity were measured using the Charlson Comorbidity Index (CCI), from 5yr before through to 5yr after starting androgen deprivation therapy (ADT).
Multivariable linear regression was used to determine differences in excess rate of CCI change before and after ADT initiation. Risk of any incremental change in CCI following ADT was assessed using multivariable Cox regression analyses.
Men on GnRH agonists experienced a greater difference in excess rate of CCI change after starting ADT than men on AA monotherapy (5.6% per yr, p
BACKGROUND: We investigated the predictors and long-term consequences of awareness time - the length of time a woman is aware of her husband's impending death from cancer. METHODS: All women (n = 506) living in Sweden under 80 years of age who lost their husband/partner owing to cancer of the prostate in 1996 or of the urinary bladder in 1995 or 1996 were followed with an anonymous postal questionnaire, 2-4 years after their loss. RESULTS: We received completed questionnaires from 379 of the widows. Of these, 55 (15%) reported an awareness time of 24 hours or less, 56 (15%) of 3-6 months and 95 (26%) of one year or more. The associations between the awareness time and morbidity were of a reverted 'J-shape,' with awareness time of 24 hours or less carrying the highest risk and 3-6/6-12 months the lowest. On comparing the awareness time of 24 hours or less with 3-6 months (preformed response category), the relative risks for anxiety were found to be 1.9. (1.0-3.6) (visual digital scale) and 4.5 (1.0-20.0) for intake of tranquillising drugs. Those not informed of their husband's fatal condition or not provided with psychological support by caregivers during their husband's last months of life had an increased risk of a short awareness time. CONCLUSIONS: During a man's terminal cancer illness, the wife's awareness time varies considerably and is influenced by information and psychological support from caregivers. A short awareness time may result in an additional and avoidable psychological trauma.
The main aim of this study was to investigate possible associations between measures of offspring size at birth in the most recent pregnancy before premenopausal breast cancer diagnosis and the risks of maternal breast cancer mortality, taking tumor characteristics into account. We also aimed to investigate if these associations are modified by age at childbirth, time since childbirth, parity, and age at diagnosis. We followed 6,019 women from their date of premenopausal breast cancer (diagnosed from 1992 to 2008) until emigration, death or December 31st, 2009, whichever occurred first. We used Cox proportional hazard regression models, adjusted for parity, age at diagnosis, and education level, to estimate associations between women pregnancy, cancer characteristics and offspring birth characteristics, and mothers' mortality risk. In stratified analyses, mortality risks were estimated by tumor stage, ER or PR status. There was no association between offspring birth weight (HR = 1.00, 95 % CI 0.99-1.01, when used as a continuous variable), birth weight for gestational age or ponderal index, and premenopausal breast cancer mortality. Similarly, in analyses stratified by tumor stage, receptor status, and time difference between last pregnancy and date of diagnosis, we found no associations between birth size and breast cancer mortality. Our findings suggest that the hypothesis that "premenopausal breast cancer mortality is associated with offspring birth characteristics in the most recent pregnancy before the diagnosis" may not be valid. In addition, these associations are not modified by tumor characteristics.
Section of Urology, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Surgical Intervention Trials Unit, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
We compared clinical characteristics and cancer specific mortality in men diagnosed with prostate cancer before vs after age 50 years.
A total of 919 men 35 to 49 years old and 45,098 men 50 to 66 years old who were diagnosed with prostate cancer between 1998 and 2012 were identified in PCBaSe (Prostate Cancer data Base Sweden). Cancer specific mortality was compared among age groups (35 to 49, 50 to 59, 60 to 63 and 64 to 66 years) with and without adjusting for cancer characteristics, comorbidity and education in a multivariable Cox proportional hazards model.
Clinical cancer characteristics indicated that most nonmetastatic cancer in men younger than 50 years was detected after prostate specific antigen testing. The proportion of nonmetastatic vs metastatic disease at diagnosis was similar in all age groups. A strong association between younger age and poor prognosis was apparent in men in whom metastatic disease was diagnosed before age 50 to 55 years. The crude and adjusted HRs of cancer specific mortality were 1.41 (95% CI 1.12-1.79) and 1.28 (95% CI 1.01-1.62) in men diagnosed before age 50 and at age 50 to 59 years, respectively. In men with nonmetastatic disease crude cancer specific mortality increased with older age but adjusted cancer specific mortality was similar in all age groups.
Our findings suggest that an aggressive form of metastatic prostate cancer is particularly common in men younger than 50 to 55 years. Genetic studies and trials of intensified systemic treatment are warranted in this patient group.
To detail the distribution of causes of death from localized prostate cancer (PCa).
The database PCBase Sweden links the Swedish National Prostate Cancer Register with other nationwide population-based healthcare registers. We selected all 57 187 men diagnosed with localized PCa between 1997 and 2009 and their 114 374 PCa-free control subjects, matched according to age and county of residence. Mortality was calculated using competing risk regression analyses, taking into account PCa risk category, age and Charlson comorbidity index (CCI).
In men with low-risk PCa, all-cause mortality was lower compared with that in corresponding PCa-free men: 10-year all-cause mortality was 18% for men diagnosed at age 70 years, with a CCI score of 0, and 21% among corresponding control subjects. Of these cases, 31% died from cardiovascular disease (CVD) compared with 37% of the corresponding control subjects. For men with low-risk PCa, 10-year PCa-mortality was 0.4, 1 and 3% when diagnosed at age 50, 60 and 70 years, respectively. PCa was the third most common cause of death (18%), after CVD (31%) and other cancers (30%). By contrast, PCa was the most common cause of death in men with intermediate- and high-risk localized PCa.
Men with low-risk PCa had lower all-cause mortality than PCa-free men because of lower CVD mortality, driven by early detection selection; however, for men with intermediate- or high-risk disease, the rate of PCa death was substantial, irrespective of CCI score, and this was even more pronounced for those diagnosed at age 50 or 60 years.
Point mutations and single nucleotide polymorphisms (SNPs) in the CDKN2A gene in bladder cancer patients have been resolved only to a limited extent. The exact frequency of mutations remains uncertain and reports on SNPs are lacking. In this population-based study we investigated mutations and polymorphisms in the CDKN2A gene in bladder cancer patients from all hospitals within the Stockholm County. Mutations were determined in 4 exons of the CDKN2A gene in tumor-tissues from 172 bladder cancer patients and 2 single nucleotide polymorphisms in the 3' UTR of the CDKN2A gene were studied in 309 cases. Missense mutations were identified in only 4 of 172 (2.3%) cases, including 1 in the germ-line. Frequencies of the 500 C-->G and 540 C-->T polymorphisms in the 3' UTR of the CDKN2A in bladder cancer cases were not statistically significantly different compared to an ethnically matched control population. The tumor-specific survival was significantly shorter in patients with either the 500 C-->G or 540 C-->T polymorphism than those with wild-type CDKN2A gene (P = 0.02). Our results corroborate the earlier findings that single base mutation is not the prime mode of inactivation of the CDKN2A gene in bladder cancer. Further, the results indicate, a role for the 3' UTR polymorphisms in the CDKN2A gene in tumor invasiveness.