[Show abstract][Hide abstract] ABSTRACT: Purpose:
Many patients and clinicians are worried that pregnancy after the diagnosis of Hodgkin lymphoma (HL) may increase the risk of relapse despite a lack of empirical evidence to support such concerns. We investigated if an association exists between pregnancy and relapse in women with a diagnosis of HL.
Materials and methods:
Using Swedish healthcare registers combined with medical records, we included 449 women who received a diagnosis of HL between 1992 and 2009 and who were age 18 to 40 years at diagnosis. Follow-up started 6 months after diagnosis, when the patients' condition was assumed to be in remission. Pregnancy-associated relapse was defined as a relapse during pregnancy or within 5 years after delivery. Hazard ratios (HRs) with 95% CIs were estimated by using the Cox proportional hazards model.
Among the 449 women, 144 (32%) became pregnant during follow-up. Overall, 47 relapses were recorded, of which one was a pregnancy-associated relapse. The adjusted HR for the comparison of the pregnancy-associated relapse rate to the non-pregnancy-associated relapse rate was 0.29 (95% CI, 0.04 to 2.18). The expected number of relapses in women with a recent pregnancy, given that they would experience the same relapse rate as that of women without a recent pregnancy, was 3.76; the observed-to-expected ratio was 0.27 (95% exact CI, 0.01 to 1.51).
We found no evidence that a pregnancy after diagnosis increases the relapse rate among women whose HL is in remission. Survivors of HL need to consider a range of factors when deciding about future reproduction. However, given the results of this study, the risk of pregnancy-associated relapse does not need to be considered.
Preview · Article · Dec 2015 · Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Emerging evidence links inflammation and immune competence to cancer progression and outcome. Few studies addressing cancer survival in the context of rheumatoid arthritis (RA) have reported reduced survival without accounting for the underlying mortality risk in RA. Whether this increased mortality is a cancer-specific phenomenon, an effect of the decreased lifespan in RA or a combination of both remains unknown.
Using Swedish register data (2001-2009), we performed a cohort study of individuals with RA (N=34 930), matched to general population comparators (N=169 740), incident cancers (N=12 676) and deaths (N=14 291). Using stratified Cox models, we estimated HRs of death associated with RA in the presence and absence of cancer, by stage and time since cancer diagnosis, for all cancers and specific sites.
In the absence of cancer, RA was associated with a doubled mortality rate (HR=2.1, 95% CI 2.0 to 2.2). In the presence of cancer, the relative effect of RA on mortality was varied by stage. For cancer (tumour, node, metastases) stages I and II at diagnosis, the relative effect of RA on mortality was the same as in the absence of cancer. For cancers diagnosed at advanced stages with absolute higher mortality, the effect decreased (HR=1.2, 95% CI 1.1 to 1.3). These associations remained across time since cancer diagnosis and were reasonably similar across cancer sites.
Much of the increase in mortality in patients with RA diagnosed with cancer seems to reside with effects of RA independently of the cancer.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
No preview · Article · May 2015 · Annals of the rheumatic diseases
[Show abstract][Hide abstract] ABSTRACT: The risk of breast cancer is at least two-fold increased in young women with a family history of breast cancer. Pregnancy has a dual effect on breast cancer risk; a short-term increase followed by a long-term protection. We investigated if the risk of breast cancer during and within 10 years following pregnancy is affected by a family history of breast cancer. We followed a cohort of women aged 15-44 years between 1963 and 2009 identified in Swedish population-based registers. Family history was defined as having a mother or sister with breast cancer. We estimated incidence rate ratios of breast cancer during pregnancy and time intervals up to 10 years post-delivery, with a focus on pregnancy-associated breast cancer (PABC), defined as breast cancer during pregnancy or within 2 years post-delivery. In 3,452,506 women, there were 15,548 cases of breast cancer (1208 were PABC). Compared to nulliparous women, the risk of breast cancer was decreased during pregnancy, similar during first year and increased during second year post-delivery. The pattern was similar in women with or without family history of breast cancer. A peak in risk was observed 5-6 years following the first birth regardless of family history. After a second birth, this peak was only present in women with a family history. Our results indicate that women with a family history of breast cancer do not have a different breast cancer risk during and within 10 years following pregnancy compared to women without a family history.
No preview · Article · Apr 2015 · Breast Cancer Research and Treatment
[Show abstract][Hide abstract] ABSTRACT: To assess whether the increased sensitivity of screening for human papillomavirus (HPV) may represent overdiagnosis and to compare the long term duration of protective effect against cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in HPV based and cytology based screening.
13 year follow-up of the Swedescreen randomised controlled trial of primary HPV screening.
Organised cervical screening programme in Sweden.
12 527 women aged 32-38 attending organised screening were enrolled and randomised to HPV and cytology double testing (intervention arm, n=6257) or to cytology only, with samples frozen for future HPV testing (control arm, n=6270).
Cumulative incidence of CIN2+ and CIN3+ (Kaplan Meier curves). Longitudinal test characteristics were calculated for cytology only, HPV testing only, and cytology and HPV testing combined, adjusting for censoring.
The increased detection of CIN2+ in the intervention arm decreased over time. After six years, the cumulative incidence of CIN3+ was similar in both trial arms, and after 11 years the cumulative incidence of CIN2+ became similar in both arms. The longitudinal sensitivity of cytology for CIN2+ in the control arm at three years was similar to the sensitivity of HPV testing in the intervention arm at five years of follow-up: 85.94% (95% confidence interval 76.85% to 91.84%) v 86.40% (79.21% to 91.37%). The sensitivity of HPV screening for CIN3+after five years was 89.34% (80.10% to 94.58%) and for cytology after three years was 92.02% (80.59% to 96.97%).
Over long term follow-up, the cumulative incidence of CIN2+ was the same for HPV screening and for cytology, implying that the increased sensitivity of HPV screening for CIN2+ reflects earlier detection rather than overdiagnosis. The low long term risks of CIN3+ among women who tested negative in HPV screening, support screening intervals of five years for such women.
[Show abstract][Hide abstract] ABSTRACT: Background:
Metastatic breast cancer is a severe condition without curative treatment. How relative and absolute risk of distant metastasis varies over time since diagnosis, as a function of treatment, age and tumour characteristics, has not been studied in detail.
A total of 9514 women under the age of 75 when diagnosed with breast cancer in Stockholm and Gotland regions during 1990–2006 were followed up for metastasis (mean follow-up=5.7 years). Time-dependent development of distant metastasis was analysed using flexible parametric survival models and presented as hazard ratio (HR) and cumulative risk.
A total of 995 (10.4%) patients developed distant metastasis; the most common sites were skeleton (32.5%) and multiple sites (28.3%). Women younger than 50 years at diagnosis, with lymph node-positive, oestrogen receptor (ER)-negative, >20 mm tumours and treated only locally, had the highest risk of distant metastasis (0–5 years' cumulative risk =0.55; 95% confidence interval (CI): 0.47–0.64). Women older than 50 years at diagnosis, with ER-positive, lymph node-negative and ⩽20-mm tumours, had the same and lowest cumulative risk of developing metastasis 0–5 and 5–10 years (cumulative risk=0.03; 95% CI: 0.02–0.04). In the period of 5–10 years after diagnosis, women with ER-positive, lymph node-positive and >20-mm tumours were at highest risk of distant recurrence. Women with ER-negative tumours showed a decline in risk during this period.
Our data show no support for discontinuation at 5 years of clinical follow-up in breast cancer patients and suggest further investigation on differential clinical follow-up for different subgroups of patients.
Full-text · Article · Jan 2014 · British Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: Background:
Familial aggregation has been shown for Alzheimer's disease (AD) and Parkinson's disease (PD) separately, and it has been hypothesized that these diseases also coaggregate in families.
The authors investigated familial coaggregation of AD and PD by conducting a systematic review and meta-analysis. PubMed was searched for relevant studies published through the end of October 2012. Three independent investigators screened publications and extracted data. Relative risk estimates of AD risk associated with family history of PD or parkinsonism, or PD risk associated with family history of AD or dementia, were summarized into metaestimates using random effects models. Heterogeneity and publication bias were tested using Higgins' and Egger's tests, respectively.
We included 16 studies in the review, with 14 included in any meta-analysis. AD risk associated with family history of PD yielded a summary hazard ratio of 1.18 (95% CI: 1.00-1.39) based on 5 reconstructed cohort studies and a summary odds ratio (OR) of 1.40 (95% CI: 0.92-2.12) based on 7 case-control studies. PD risk associated with family history of AD yielded a summary OR of 0.75 (95% CI: 0.49-1.16) based on 3 studies. There was no significant heterogeneity among studies, nor significant publication bias.
There may be familial coaggregation of AD and PD, although the association was modest and only apparent when studying AD risk associated with family history of PD.
No preview · Article · Nov 2013 · Neuroepidemiology
[Show abstract][Hide abstract] ABSTRACT: To investigate the contribution of shared familial risk to the co-occurrence of dementia and parkinsonism by studying familial co-aggregation of Alzheimer's disease (AD) and Parkinson's disease (PD). Using Swedish population-based registers we constructed two cohorts; a first-degree relative cohort of persons born 1932-1960 (n = 2,775,332) and a spouse cohort of persons born 1890-1960 (n = 4,736,006). Study persons were followed up between 1969 and 2009 in the National Patient and Cause of Death Registers. We modeled the association between incidence of disease and having at least one affected relative using Cox proportional hazard regression that estimated hazard ratios (HRs) with 95 % confidence intervals (CIs) adjusted for age, sex and number of relatives. Within each disorder; dementia, AD, parkinsonian disorders and PD, there was a strong association between risk of disease and having at least one affected sibling or parent. There was also a modest shared familial risk between the diseases; risk of parkinsonian disorders was associated with having a sibling with AD (HR 1.35, 95 % CI 1.11-1.65) and risk of dementia was associated with having a sibling with PD (HR 1.20, 95 % CI 1.02-1.41). There were no meaningful familial risks among spouses. The risk of co-occurring dementia in PD was considerably increased (HR 2.83, 95 % CI 2.76-2.89). There is strong familial aggregation within dementia, AD, parkinsonian disorders and PD, and modest familial co-aggregation between dementia and parkinsonism. Thus, co-occurrence of dementia and parkinsonism is not primarily caused by shared familial risk between AD and PD.
No preview · Article · Nov 2013 · European Journal of Epidemiology
[Show abstract][Hide abstract] ABSTRACT: Converging evidence indicates that women with pregnancy-associated breast cancer (PABC) have increased mortality compared to women with breast cancer not diagnosed near pregnancy (non-PABC). Our aim was to investigate if the stage distribution differs between PABC and non-PABC and if stage at diagnosis can explain the poorer prognosis observed among women with PABC. We identified 3,282 breast cancers in women aged 15-44 years at diagnosis for whom staging data (tumor size, nodal involvement, metastasis) were available in the Swedish Cancer Register between 2002 and 2009. Information on reproductive history and vital status was obtained from the Multi-Generation Register and the Cause of Death Register. PABC was defined as breast cancers diagnosed during pregnancy and up to 2 years after delivery (n = 317). Non-PABC was defined as cases diagnosed before pregnancy or more than 2 years postpartum. Stage distributions were compared between PABC and non-PABC, and mortality rates were modeled using Cox regression. Compared to women with non-PABC, the mortality was almost 50 % higher in women with PABC [unadjusted hazard ratio (HR) 1.47 (95 % CI 1.04-2.08)], a difference which was reduced after adjustment for age and calendar year of diagnosis [HR 1.27 (95 % CI 0.88-1.83)]. Although advanced stage of breast cancer at diagnosis was more common among PABC than among non-PABC, further adjustment for stage only slightly reduced the HR [1.22 (95 % CI 0.84-1.78)]. The difference in mortality between PABC and non-PABC was more pronounced among women above 35 years and among women with PABC diagnosed within 1 year postpartum. Age, rather than stage at diagnosis, appears to act as the principal driver of the increased mortality observed in women with PABC. However, these findings do not preclude an untoward influence on mortality by pregnancy-associated factors affecting tumor aggressiveness and progression.
No preview · Article · Apr 2013 · Breast Cancer Research and Treatment
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The incidence of bladder cancer (BCa) is substantially lower in women than in men, a difference that cannot be fully explained by established risk factors. Several studies suggest that hormonal and reproductive factors play a role in the development of BCa. OBJECTIVE: To examine possible associations between patterns of childbearing and the risk of BCa. DESIGN, SETTING, AND PARTICIPANTS: This cohort study encompassed >2 million women for whom information on reproductive history and BCa incidence was retrieved from Swedish population-based registers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incidence rate ratios (IRRs) of BCa were estimated using Cox proportional hazards modelling. The exposures under investigation were parity and age at first birth, adjusted for education and history of chronic obstructive lung disease (COLD). RESULTS AND LIMITATIONS: Among 2 009 811 women in the cohort, 2860 incident cases of BCa were identified. Parous women had lower incidence of BCa compared with nulliparous women (adjusted IRR: 0.80; 95% confidence interval [CI], 0.72-0.89). Moreover, the incidence was 15% lower in women with two children and 24% lower in women with three or more children compared with uniparous women. Compared with women aged 20-24 at first childbirth, the incidence was elevated in women with a first birth before age 20 (adjusted IRR: 1.16; 95% CI, 1.05-1.29). The risk of BCa was elevated in women with low education and among women with a history of COLD. Absence of data on menstrual history, use of exogenous hormones, and smoking was a limitation of the study. CONCLUSIONS: The incidence of BCa decreased with increasing parity and older age at first birth. Although smoking habits may partly explain some of the associations, our findings provide support for yet-to-be-identified protective mechanisms associated with childbearing, possibly mediated by hormonal or structural changes following pregnancy.
No preview · Article · Jan 2013 · European Urology
[Show abstract][Hide abstract] ABSTRACT: It is unclear whether estrogen receptor (ER)-status of first primary breast cancer is associated with risk of metachronous (non-simultaneous) contralateral breast cancer (CBC), and to what extent endocrine therapy affects this association.
We studied the effect of ER-status of the first cancer on the risk of CBC overall, and for different ER-subtypes of CBC, using a large, population-based cohort. The cohort consisted of all women diagnosed with breast cancer in the Stockholm region 1976-2005; 25715 patients, of whom 940 suffered CBC. The relative risk was analyzed mainly using standardized incidence ratios (SIR).
WOMEN WITH BREAST CANCER HAD A DOUBLED RISK OF CBC COMPARED TO THE RISK OF BREAST CANCER IN THE GENERAL FEMALE POPULATION (SIR: 2.22 [2.08-2.36]), for women with a previous ER-positive cancer: SIR = 2.30 (95% CI:2.11-2.50) and for women with a previous ER-negative cancer: SIR = 2.17 (95% CI:1.82-2.55). The relative risk of ER-positive and ER-negative CBC was very similar for women with ER-positive first cancer (SIR = 2.02 [95%CI: 1.80-2.27] and SIR = 1.89 [95%CI: 1.46-2.41] respectively) while for patients with ER-negative first cancer the relative risk was significantly different (SIR = 1.27 [95% CI:0.94-1.68] for ER-positive CBC and SIR = 4.96 [95%CI:3.67-6.56] for ER-negative CBC). Patients with ER-positive first cancer who received hormone therapy still had a significantly higher risk of CBC than the risk of breast cancer for the general female population (SIR = 1.74 [95% CI:1.47-2.03]).
The risk of CBC for a breast cancer patient is increased to about two-fold, compared to the risk of breast cancer in the general female population. This excess risk decreases, but does not disappear, with adjuvant endocrine therapy. Patients with ER-positive first cancers have an increased risk for CBC of both ER subtypes, while patients with ER-negative first cancer have a specifically increased risk of ER-negative CBC.
[Show abstract][Hide abstract] ABSTRACT: To improve confounder adjustments, observational studies are often matched on
potential confounders. While matched case-control studies are common and well
covered in the literature, our focus here is on matched cohort studies, which
are less common and sparsely discussed in the literature. Matched data also
arise naturally in twin studies, as a cohort of exposure-discordant twins can
be viewed as being matched on a large number of potential confounders. The
analysis of twin studies will be given special attention. We give an overview
of various analysis methods for matched cohort studies with binary exposures
and binary outcomes. In particular, our aim is to answer the following
questions: (1) What are the target parameters in the common analysis methods?
(2) What are the underlying assumptions in these methods? (3) How do the
methods compare in terms of statistical power?
Full-text · Article · Oct 2012 · Statistical Science
[Show abstract][Hide abstract] ABSTRACT: Swedish population-based national health registers are widely used data sources in epidemiological research. Register-based diagnoses of Parkinson's disease have not been validated against clinical information.
Parkinson's disease (PD) and other parkinsonian disorder diagnoses were ascertained in two registers, i.e. the National Patient Register (NPR) and the Cause of Death Register (CDR). Diagnoses were validated in terms of accuracy (positive predictive value) and sensitivity against data from a population-based study of PD in 1998-2004 that screened more than 35,000 persons and identified 194 cases of parkinsonian disorders including 132 PD cases (the gold standard for the purposes of this study).
Accuracy for any parkinsonian disorder diagnoses was 88.0% in the NPR and 94.4% in the CDR. Accuracy of PD diagnoses was 70.8% in the NPR and 66.7% in the CDR. Misclassification between differential parkinsonian diagnoses was common. The accuracy of PD diagnoses in the NPR improved to 83.0% by restricting the definition to primary diagnoses only. The sensitivity of PD diagnoses in the NPR and CDR combined was 83.1%, with a mean time to detection of 6.9 years.
Population-based national health registers are valid data sources in epidemiological studies of PD or parkinsonian disorder etiology but are less suitable in studies of incidence or prevalence.
[Show abstract][Hide abstract] ABSTRACT: The proportion of women living with a diagnosis of breast cancer in developed countries is increasing. Because breast cancer-specific deaths decrease with time since diagnosis, it is important to assess the burden of other causes of death in women diagnosed with breast cancer.
Different causes of death within 10 years from diagnosis were assessed in 12,850 women younger than 75 years of age with stage 1 to 3 breast cancer diagnosed in Stockholm and Gotland regions 1990 to 2006. Flexible parametric survival models were used to estimate hazard ratios over time since diagnosis by tumor characteristics and age at diagnosis.
The proportion of deaths attributed to breast cancer ranged from 95.0% among women younger than age 45 years at diagnosis to 44.5% among women age 65 to 74 years. The proportions of circulatory system-specific deaths and deaths resulting from other causes increased with older age at diagnosis. Patients with one to three positive lymph nodes were more likely to die as a result of breast cancer during the first 10 years of follow-up compared with women without positive lymph nodes. Women with estrogen receptor (ER) -positive tumors had the same risk of dying as a result of breast cancer 5 years after diagnosis compared with women with ER-negative tumors.
Lymph node negativity is an important long-term predictor of more favorable prognosis. The nature of the relationship between ER status and risk of dying as a result of breast cancer after 5 years of follow-up requires further investigation. Circulatory system diseases are an important cause of death, especially in women diagnosed with breast cancer at an older age.