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Background: Survival of patients with colon and rectal cancer has improved in all Nordic countries during the past decades. The aim of this study was to further assess survival trends in patients with colon and rectal cancer in the Nordic countries by age at diagnosis and to present additional survival measures. Methods: Data on colon and rectal cancer cases diagnosed in the Nordic countries between 1990 and 2016 were obtained from the NORDCAN database. Relative survival was estimated using flexible parametric models. Both age-standardized and age-specific measures for women and men were estimated from the models, as well as reference-adjusted crude probabilities of death and life-years lost. Results: The five-year age-standardized relative survival of colon and rectal cancer patients continued to improve for women and men in all Nordic countries, from around 50% in 1990 to about 70% at the end of the study period. In general, survival was similar across age and sex. The largest improvement was seen for Danish men and women with rectal cancer, from 41% to 69% and from 43% to 71%, respectively. The age-standardized and reference-adjusted five-year crude probability of death in colon cancer ranged from 30% to 36% across countries, and for rectal cancer from 20% to 33%. The average number of age-standardized and reference-adjusted life-years lost ranged between six and nine years. Conclusion: There were substantial improvements in colon and rectal cancer survival in all Nordic countries 1990-2016. Of special note is that the previously observed survival disadvantage in Denmark is no longer present. (C) 2022 The Author(s). Published by Elsevier Ltd.

Supplementary Figure 1 legend, Supplementary Tables 1-7. Supplementary Figure 1 legend. Supplementary Table 1. ICD codes for venous thromboembolism. Supplementary Table 2. Single nucleotide polymorphisms included in the VTE polygenic risk score. Supplementary Table 3. Patient, tumor and treatment characteristics of the study population. Supplementary Table 4. Chemotherapy and VTE risk in breast cancer patients - analyses by chemotherapy agent and stratified by endocrine therapy. Supplementary Table 5. Venous thromboembolism risk in breast cancer patients by chemotherapy and FVL carriership. Supplementary Table 6. Hazard ratios for venous thromboembolism in breast cancer patients by chemotherapy and genetic susceptibility - sensitivity analyses. Supplementary Table 7. Cumulative incidences of VTE by chemotherapy and genetic susceptibility - sensitivity analyses.

Cumulative incidence of VTE by chemotherapy and FVL carriership, overall and stratified by age at diagnosis.

Purpose: Venous thromboembolism (VTE) is highly heritable and a serious complication of cancer and its treatment. We examined the individual and joint effects of chemotherapy and genetic susceptibility on VTE risk in patients with breast cancer.Experimental Design: A Swedish population-based study including 4,261 women diagnosed with primary invasive breast cancer between 2001 and 2008 in Stockholm, followed until 2012. Risk stratification by chemotherapy and genetic susceptibility [a polygenic risk score (PRS), including nine established VTE loci] was assessed using Kaplan–Meier and flexible parametric survival analyses, adjusting for patient, tumor, and treatment characteristics.Results: In total, 276 patients experienced a VTE event during a median follow-up of 7.6 years. Patients receiving chemotherapy [HR (95% CI) = 1.98; 1.40–2.80] and patients in the highest 5% of the PRS [HR (95% CI) = 1.90; 1.24–2.91] were at increased risk of developing VTE. Chemotherapy and PRS acted independently on VTE risk and the 1-year cumulative incidence in patients carrying both risk factors was 9.5% compared with 1.3% in patients not having these risk factors (P < 0.001). Stratified analyses by age showed that the risk-increasing effect of PRS was stronger in older patients (P interaction = 0.04), resulting in an excess risk among genetically susceptible patients receiving chemotherapy aged ≥ 60 years (1-year cumulative incidence = 25.0%).Conclusions: Risk stratification by chemotherapy and genetic susceptibility identifies patients with breast cancer at high VTE risk, who could potentially benefit from thromboprophylaxis. Our results further suggest that genetic testing is more informative in older patients with breast cancer. Clin Cancer Res; 22(21); 5249–55. ©2016 AACR.

BACKGROUND: Several metals act as endocrine disruptors, but there are few large longitudinal studies about associations with puberty onset.OBJECTIVES: We evaluated whether early life cadmium, lead, and arsenic exposure was associated with timing of menarche. METHODS: In a mother-child cohort in rural Bangladesh (n = 935), the exposure was assessed by concentrations in maternal erythrocytes in early pregnancy and in girls' urine at 5 and 10 years of age using inductively coupled plasma mass spectrometry. The girls were interviewed twice, at aver-age ages 13.3 [standard deviation eth SD THORN = 0.43] and 13.8 (SD = 0.43) y, and the date of menarche, if present, was recorded. Associations were assessed using Kaplan-Meier analysis and multivariable-adjusted Cox regression.RESULTS: In total, 77% of the girls (n = 717) had reached menarche by the second follow-up. The median age of menarche among all girls was 13.0 y (25th-75th percentiles: 12.4-13.7 y). At 10 years of age, median urinary cadmium was 0.25 mu g/L (5th-95th percentiles: 0.087-0.72 mu g/L), lead 1.6 mu g/L (0.70-4.2 mu g/L), and arsenic 54 mu g/L (19-395 mu g/L). Given the same age, girls in the highest quartile of urinary cadmium at 5 and 10 years of age had a lower rate of menarche than girls in the lowest quartile, with an adjusted hazard ratio of (HR) 0.80 (95% CI: 0.62, 1.01) at 5 years of age, and 0.77 (95% CI: 0.60, 0.98) at 10 years of age. This implies that girls in the highest cadmium exposure quartile during childhood had a higher age at menarche. Comparing girls in the highest to the lowest quartile of urinary lead at 10 years of age, the former had a higher rate of menarche [adjusted HR = 1.23 (95% CI: 0.97, 1.56)], implying lower age at menarche, whereas there was no association with urinary lead at 5 years of age. Girls born to mothers in the highest quartile of erythrocyte arsenic during pregnancy were less likely to have attained menarche than girls born to mothers in the low-est quartile [adjusted HR = 0.79 (95% CI: 0.62, 0.99)]. No association was found with girls' urinary arsenic exposure.DISCUSSION: Long-term childhood cadmium exposure was associated with later menarche, whereas the associations with child lead exposure were inconclusive. Maternal exposure to arsenic, but not cadmium or lead, was associated with later menarche. https://doi.org/10.1289/EHP11121

Background Pregnancy-associated cancer (PAC) is increasing over time in many countries. We provide a comprehensive, population-based overview of cancer survival in women with PAC across five decades. Methods We performed a nationwide cohort study of 121,382 women diagnosed with cancer at age 15–49 between 1970 and 2018 using birth and cancer registers in Sweden. Pregnancy-associated cancer was defined as diagnosed during pregnancy and within one year of delivery, while non-PAC was outside this window. Cox regression estimated adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) comparing cancer mortality for PAC versus non-PAC. Results In total, 5079 women had a diagnosis of PAC. Cutaneous malignant melanoma, breast, cervical, thyroid and central nervous system (CNS) were the most common sites of PAC. A higher cancer mortality was observed in PAC versus non-PAC for breast (HR = 1.72, 95% CI 1.54–1.93) and uterine cancer (myometrium/unspecified) (8.62, 2.80–26.53), in which all PAC deaths were uterine sarcomas. Increased mortality was also observed in upper digestive tract cancer diagnosed during pregnancy and colon cancer diagnosed during first year after delivery. Contrary, the HR for CNS tumours was significantly decreased (0.71, 0.55–0.91). Survival after PAC improved for most sites over time, with survival after breast cancer during pregnancy in recent years being similar to that of non-pregnancy associated breast cancer. Conclusion For the majority of sites, PAC was not associated with poorer prognosis compared to non-PAC, a finding which was stable over time. The main exceptions were breast cancer and rarer cancers, such as uterine sarcoma.

Background The natural history of breast cancer among BRCA2 carriers has not been clearly established. In a previous study from Iceland, positive ER status was a negative prognostic factor. We sought to identify factors that predicted survival after invasive breast cancer in an expanded cohort of BRCA2 carriers. Methods We studied 608 women with invasive breast cancer and a pathogenic BRCA2 mutation (variant) from four Nordic countries. Information on prognostic factors and treatment was retrieved from health records and by analysis of archived tissue specimens. Hazard ratios (HR) were estimated for breast cancer-specific survival using Cox regression. Results About 77% of cancers were ER-positive, with the highest proportion (83%) in patients under 40 years. ER-positive breast cancers were more likely to be node-positive (59%) than ER-negative cancers (34%) (P P = 0.03); thereafter, the effect was adverse (HR = 1.91; 95% CI 1.07–3.39, P = 0.03). The adverse effect of positive ER status was limited to women who did not undergo endocrine treatment (HR = 2.36; 95% CI 1.26–4.44, P = 0.01) and patients with intact ovaries (HR = 1.99; 95% CI 1.11–3.59, P = 0.02). Conclusions The adverse effect of a positive ER status in BRCA2 carriers with breast cancer may be contingent on exposure to ovarian hormones.

Background Data on pregnancy outcomes in women with psoriasis are conflicting. Objective We examined whether maternal psoriasis affects the risk of adverse maternal and pregnancy outcomes. Methods We used population-based data to compare reproductive patterns in women with and without psoriasis. Odds ratios (ORs) with 95% confidence intervals (CIs) for adverse outcomes were estimated with adjustments for maternal age, period of childbirth, smoking, and prepregnancy body mass index. Results Compared with women without psoriasis, women with psoriasis were younger at first birth and had longer interpregnancy intervals but did not differ in final parity. Risk estimates in women with psoriasis were elevated for pregnancy hypertension (OR, 1.37; 95% CI, 1.19-1.58), premature rupture of membranes (OR, 1.15; 95% CI, 1.04-1.27), large for gestational age (OR, 1.11; 95% CI, 1.01-1.21), cleft palate (OR, 1.69; 95% CI, 1.07-2.66), and unspecified malformations (OR, 1.08; 95% CI, 1.01-1.16). Limitations No information was available on lifestyle, disease severity, or type and duration of treatment. Small numbers hampered the assessment of rare outcomes. Conclusion Although there was no evidence that fertility is negatively affected, women with psoriasis were at an increased risk of several adverse maternal and pregnancy outcomes. Our findings add to a growing body of evidence that pregnancies in women with psoriasis need special monitoring.

Women with high socioeconomic status (SES) have the highest incidence rates of breast cancer. We wanted to determine if high SES women only have higher rates of localized disease, or whether they also have higher rates of non-localized disease. To study this, we used data on a young population with universal health care, but not offered screening.Using individually linked registry data, we compared stage-specific breast cancer incidence, by education level and income quintile, in a Norwegian cohort of 1,106,863 women aged 30-48 years during 2000-2015 (Incidence of localized and regional disease increased significantly with increasing education and income level. Incidence of distant stage disease did not vary significantly by education level but was significantly reduced in the four highest compared to the lowest income quintile. The age-standardized rates for tertiary versus compulsory educated women were: localized 28.2 vs 19.8, regional 50.8 vs 40.4 and distant 2.3 vs 2.6 per 100,000 person-years. The adjusted incidence rate ratios (tertiary versus compulsory) were: localized 1.40 (95% CI 1.25-1.56), regional 1.25 (1.15-1.35), distant 0.90 (0.64-1.26). The age-standardized rates for women in the highest versus lowest income quintile were: localized 28.9 vs 17.7, regional 52.8 vs 41.5 and distant 2.3 vs 3.2 per 100,000 person-years. The adjusted incidence rate ratios (highest versus lowest quintile) were: localized 1.63 (1.42-1.87), regional 1.27 (1.09-1.32), distant 0.64 (0.43-0.94).Increased breast cancer rates among young high SES women is not just increased detection of small localized tumors, but also increased incidence of tumors with regional spread. The higher incidence of young high SES women is therefore real and not only because of excessive screening.

Study question Are the previously reported greater risks of childhood asthma in children conceived by assisted reproductive techniques due to the intervention or unmeasured parental confounding? Summary answer After accounting for both measured and unmeasured parental factors we found no indication that the use of assisted reproductive techniques increases children’s risk of asthma. What is known already Several earlier studies have reported a higher risk of childhood asthma among children conceived by ART. However, only one previous study has attempted a sibling comparison to account for infertility as well as parental background factors, and their findings need to be replicated. Little is thus known on what underlies the higher risk of childhood asthma. Study design, size, duration In this nationwide register-based cohort, we identified all 1,671,532 live births between 1997 and 2013 in the Swedish Medical Birth Register (MBR) and followed them to the end of 2018. Participants/materials, setting, methods Infertility and ART use were ascertained from IVF clinic reporting, clinical diagnosis, and maternal self-report during the first antenatal visit. Childhood asthma was identified from diagnosis in hospitalization and outpatient specialist care records, and dispensations of asthma medication. Cox proportional hazard regression was used to estimate the association of ART and asthma in the population, in children of couples with known infertility, and in a sample of siblings conceived with and without ART (differentially exposed). Main results and the role of chance Of the 1,671,532 live births in the cohort, 11.7% were born to couples with known infertility, and 3.5% were conceived with ART. Compared with all other children, children conceived by ART had a small, elevated risk of asthma (adjusted hazard ratio (aHR)=1.14, 95% Confidence interval (CI) 1.11 to 1.16). When the comparison was restricted to children of couples with known infertility the difference in risk was even smaller (aHR=1.07, 95% CI 1.05 to 1.10), and in the comparison of siblings conceived with and without ART no difference in risk was seen (aHR=0.98, 95% CI 0.86 to 1.13). Among children conceived with ART, those in which intra-cytoplasmic sperm injection (ICSI) had been used had a slightly lower risk of asthma (aHR=0.93, 95% CI 0.90 to 0.97), and no difference in risk was seen between use of fresh and frozen-thawed embryo transfer. Limitations, reasons for caution Sibling comparison is sensitive to potential misclassification, unmeasured confounding and carryover effects, so should be interpreted with this in mind. Differences in treatment implementation across time and settings could affect the ability to extrapolate the conclusions to another clinical context (where e.g., single-embryo transfer policy is not implemented). Wider implications of the findings: This study found a modestly elevated risk of asthma in children conceived with ART to be largely explained by confounding from parental background factors. There were further no indications of adverse influence from increasingly utilized ART procedures such as ICSI or embryo-freezing, with respect to asthma in childhood. Trial registration number Not applicable

OBJECTIVES To examine the long-term impact of assisted reproductive techniques (ART) on offspring neurodevelopment, accounting for parental factors and the role of infertility. METHODS Linkage of national registers allowed follow-up of >2.4 million children born in Sweden 1986–2012. Information on ART was retrieved from fertility clinics, medical records, and maternal self-report. Attention-deficit/hyperactivity disorder (ADHD) was identified from specialist diagnosis and/or use of medication through 2018. School performance was assessed from records of ninth year final grade averages (0–20) and eligibility for upper secondary school through 2017. RESULTS Children conceived with ART had lower risk of ADHD (hazard ratio 0.83; 95% confidence interval [CI]: 0.80 to 0.87) and did better in school (grade mean difference 1.15; 95% CI: 1.09 to 1.21 and eligibility odds ratio 1.53; 95% CI: 1.45 to 1.63) compared with all other children. Differences in parental characteristics explained and even reversed associations, whereas no disadvantage was seen when the comparison was restricted to children of couples with known infertility (adjusted hazard ratio 0.95; 95% CI: 0.90 to 1.00, adjusted mean difference 0.05; 95% CI: −0.01 to 0.11, and adjusted odds ratio 1.03; 95% CI: 0.96 to 1.10). Among children conceived with ART, there was furthermore no indication that intracytoplasmic sperm injection (compared with standard in vitro fertilization) or frozen (compared with fresh) embryo transfer had any adverse influence. CONCLUSIONS With this nationwide, long-term follow-up, we provide additional reassurance concerning offspring neurodevelopment after use of ART, finding no indication for concern about risk of ADHD or school performance in adolescence.

The study aimed to investigate if assisted reproductive technology (ART) treatment or a diagnosis of infertility were associated with the risk of ovarian cancer or borderline ovarian tumors (BOT) in parous women. In a population-based register study of 1,340,097 women with a first live birth in Sweden 1982–2012, the relationship between ART treatments, infertility and incidence of ovarian cancer or BOT were investigated using Cox regression analysis. In the cohort, 38,025 women gave birth following ART, 49,208 following an infertility diagnosis but no ART and 1,252,864 without infertility diagnosis or ART. During follow-up, 991 women were diagnosed with ovarian cancer and 747 with BOT. Women who gave birth following ART had higher incidence of both ovarian cancer (adjusted hazard ratio [aHR] 2.43, 95% confidence interval [CI] 1.73–3.42) and BOT (aHR 1.91, 95% CI 1.27–2.86), compared to women without infertility. Compared to women with infertility diagnoses and non-ART births, women with ART births also had a higher incidence of ovarian cancer (aHR 1.79, 95% CI 1.18–2.71) and BOT (aHR 1.48, 95% CI 0.90–2.44). Our results suggest that women who have gone through ART have a higher risk of ovarian cancer and BOT. At least part of that risk seems to be due to the underlying infertility and not the treatment per se, since the increased risk was smaller when comparing to other infertile women. As ART treatments are becoming more common and ovarian cancer usually occur in women of advanced age, larger studies with longer follow-up are needed in order to confirm or refute our findings. Electronic supplementary material The online version of this article (10.1007/s10654-019-00540-3) contains supplementary material, which is available to authorized users.

Background Previous studies indicate a higher risk of comorbidity in men with infertility; however, research on mortality is scarce and the few studies that do exist have rarely differentiated between infertility and infertility-related diagnoses. Objective To examine mortality in men with an infertility or infertility-related diagnosis. Design setting and participants Population-based cohort study of men born in 1944-1992 in Sweden. We used Cox regression estimated hazard ratios (HRs) for infertility while adjusting for number of children, education, year of birth, country of birth, diabetes, hypertension, liver disease and end-stage renal disease. In all, 43,598 men with a diagnosis of infertility and 57,733 men with an infertility-related diagnosis were compared with 2,762,254 men (reference group) without such diagnoses. Outcome measures All-cause and cause-specific mortality at age 20 to 69 years. Results and limitations The 2,863,585 men in the study were followed for a median time of 22.0 years. During follow-up, 439 men with a diagnosis of infertility died, corresponding to a crude incidence rate of 1.56 deaths per 1,000 person-years. These figures can be compared with 1,400 deaths in men with an infertility-related diagnosis (1.96 deaths/1,000 person-years) and 99,463 deaths in reference individuals (2.17 deaths/1,000 person-years). Overall, men with a diagnosis of infertility did not have a higher risk of death (adjusted [a]HR=0.98; 95% confidence interval [95% CI]=0.89-1.08), but had a higher risk of death before age 30 (20-29 years) (aHR=3.26; 95% CI=2.42-4.41). This early excess mortality was largely explained by cancer diagnosed before infertility. Having an infertility-related diagnosis was associated with death (aHR=1.23; 95% CI=1.17-1.30). Limitations include the lack of general screening for infertility in Sweden and the lack of information on semen parameters. Conclusion Men with a diagnosis of infertility are not at a higher risk of death than the general population, although having a diagnosis related to infertility may be linked to a higher risk of death. Patient summary Men with a diagnosis of infertility do not seem to have a higher risk of death though an infertility-related diagnosis in men is associated with the risk of death.

Objectives Women diagnosed with breast cancer during working age are at increased risk of permanent absence from work, but the underlying medical causes have rarely been studied. We examined the risk of cause-specific sick leave, disability pension, and the competing event death after a breast cancer diagnosis in a population-based cohort study. Materials and methods From the Breast Cancer Data Base Sweden, we identified 16,603 women diagnosed with stage I-III breast cancer between 2000 and 2012, and 63,773 control women. Using multi-state modelling, we calculated probabilities and durations of sick leave, disability pension, and death by registered cause, together with cause-specific hazard ratios. Results Five years after diagnosis, causes other than cancer accounted for around half of all sick leave (3.5% out of 6.8% of women) and disability pension (1.4% out of 2.6%) in women with breast cancer. Compared with control women, women with breast cancer were at increased risk of sick leave and disability pension due to mental disorders (HR 1.24, 95% CI 1.15–1.33 and HR 1.54, 95% CI 1.29–1.85, respectively) and disability pension due to inflammatory diseases (HR 1.46, 95% CI 1.05–2.03). The risk of sick leave and disability pension due to cardiovascular disease was also elevated, although only statistically significant for disability pension in women diagnosed after 2005 (HR 2.24, 95% CI 1.22–4.13). Conclusion Follow-up, support, and rehabilitation programs for women diagnosed with breast cancer must address a wide range of psychological and physical conditions to limit the consequences on working life.

Some studies have suggested that infertility is a risk factor for endometrial, ovarian and breast cancer. The study aimed to create a comprehensive picture of the association between infertility and the risk of ovarian, endometrial and breast cancer, and whether any association could be explained by ovulatory disturbances, endometriosis or nulliparity. In a population-based cohort of 2,882,847 women, cox regression analysis was used to investigate cancer incidence among infertile women. Overall, infertility was associated with a higher incidence rate of ovarian (adjusted hazard ratio [aHR] 1.53, 95% confidence interval [CI] 1.38–1.71) and endometrial cancer (aHR 1.25, 95% CI 1.11–1.40), but not of breast cancer (aHR 0.96, 95% CI 0.92–1.01). Ovarian cancer incidence was higher in women diagnosed with endometriosis, and in nulliparous women with ovulatory disturbances, compared to women with none of the diagnoses. Endometrial cancer incidence was higher in women with ovulatory disturbances, but not in women with endometriosis. These findings suggest that infertility could have long-term consequences of importance to physicians and public health workers. Electronic supplementary material The online version of this article (10.1007/s10654-018-0474-9) contains supplementary material, which is available to authorized users.

BACKGROUND Due to recent changes in the legal framework, access to fertility preservation (FP) for transgender individuals has opened up in several countries. In Sweden and the Nordic countries, fertility preservation for medical reasons is fully reimbursed as part of the established tax-funded healthcare services. As this issue is relatively new, procedures for FP have seldom been reported in the transgender patient population. The very limited literature has indicated that transgender women may have poorer sperm quality than cisgender men when assessing samples aimed at semen banking. OBJECTIVES To assess sperm quality parameters of semen samples provided for FP by transgender women before or after gender affirming hormone therapy (GAHT), and to compare sperm quality with a reference population of unscreened men defined by the World Health Organization (WHO). Additionally, we aimed to describe referral patterns over calendar time and estimate time from referral to semen cryopreservation. MATERIAL AND METHODS Prospective cohort study of 212 transgender women referred for FP to the Reproductive Medicine Clinic of Karolinska University Hospital, Sweden, between 2013 and 2018. Among 177 individuals that provided semen samples for cryopreservation, 16 had previously received GAHT. RESULTS Individuals with previous GAHT presented with significantly lower total sperm count than individuals without GAHT (p = 0.002). However, higher proportions of sperm abnormalities were also noted among individuals who had not undergone previous GAHT, compared to the WHO reference population (p

BackgroundIn breast cancer, immunohistochemistry (IHC) subtypes, together with grade and stage, are well-known independent predictors of breast cancer death. Given the immense changes in breast cancer treatment and survival over time, we used recent population-based data to test the combined influence of IHC subtypes, grade and stage on breast cancer death.MethodsWe identified 24,137 women with invasive breast cancer aged 20 to 74 between 2005 and 2015 in the database of the Cancer Registry of Norway. Kaplan-Meier curves, mortality rates and adjusted hazard ratios for breast cancer death were estimated by IHC subtypes, grade, tumour size and nodal status during 13 years of follow-up.ResultsWithin all IHC subtypes, grade, tumour size and nodal status were independent predictors of breast cancer death. When combining all prognostic factors, the risk of death was 20- to 40-fold higher in the worst groups compared to the group with the smallest size, low grade and ER+PR+HER2− status. Among node-negative ER+HER2− tumours, larger size conferred a significantly increased breast cancer mortality. ER+PR−HER2− tumours of high grade and advanced stage showed particularly high breast cancer mortality similar to TNBC. When examining early versus late mortality, grade, size and nodal status explained most of the late (> 5 years) mortality among ER+ subtypes.ConclusionsThere is a wide range of risks of dying from breast cancer, also across small breast tumours of low/intermediate grade, and among node-negative tumours. Thus, even with modern breast cancer treatment, stage, grade and molecular subtype (reflected by IHC subtypes) matter for prognosis.

Background Differences in cancer survival between the Nordic countries have previously been reported. The aim of this study was to examine whether these differences in outcome remain, based on updated information from five national cancer registers. Materials and methods The data used for the analysis was from the NORDCAN database focusing on nine common cancers diagnosed 1990-2016 in Denmark, Finland, Iceland, Norway and Sweden with maximum follow-up through 2017. Relative survival (RS) was estimated at 1 and 5 years using flexible parametric RS models, and percentage point differences between the earliest and latest years available were calculated. Results A consistent improvement in both 1- and 5-year RS was found for most studied sites across all countries. Previously observed differences between the countries have been attenuated. The improvements were particularly pronounced in Denmark that now has cancer survival similar to the other Nordic countries. Conclusion The reasons for the observed improvements in cancer survival are likely multifactorial, including earlier diagnosis, improved treatment options, implementation of national cancer plans, uniform national cancer care guidelines and standardized patient pathways. The previous survival disadvantage in Denmark is no longer present for most sites. Continuous monitoring of cancer survival is of importance to assess the impact of changes in policies and the effectiveness of health care systems.

Trewin CB, Johansson ALV, Hjerkind KV, Strand BH, Kiserud CE, Ursin G (2020) Stage-specific survival has improved for young breast cancer patients since 2000: but not equally. Breast Cancer Res Treat 182(2):477–489 Article Google Scholar Sorum R, Hofvind S, Skaane P, Haldorsen T (2010) Trends in incidence of ductal carcinoma in situ: the effect of a population-based screening programme. Breast 16:499–505 Article Google Scholar Lousdal ML, Kristiansen IS, Moller B, Stovring H (2016) Effect of organised mammography screening on stage specific incidence in Norway: population study. BJC 114:590–596 Article Google Scholar Strand BH, Tverdal AA, Claussen B, Zahl PH (2005) Is birth history the key to highly educated women’s higher breast cancer mortality: a follow-up study of 500 000 women aged 35–54. Int J Cancer 117:1002–1006 Lousdal ML, Lash TL, Flanders WD, Brookhart MA, Kristiansen IS, Kalager M, Stovring H (2020) Negative controls to detect uncontrolled confounding in observational studies of mammography screening comparing participants and non-participants. Int J Epidemiol 49:2031–2042 Article Google Scholar Download references No funding for research and no funding from medical companies. Domain for Mental and Physical Health, Norwegian Institute of Public Health, Skoyen, P.O. Box 222, 0213, Oslo, Norway Per-Henrik Zahl Faculty of Medicine, Institute of Health and Society, University of Oslo, Blindern, P.O. Box 1130, 0318, Oslo, Norway Ivar Sonbo Kristiansen You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to Per-Henrik Zahl. The authors have no potential conflict of interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions Zahl, P., Kristiansen, I.S. Re: Stage-specific survival has improved for young breast cancer patients since 2000: but not equally?. Breast Cancer Res Treat (2020). https://doi.org/10.1007/s10549-020-05941-7 Download citation Received: 07 September 2020 Accepted: 12 September 2020 Published: 24 September 2020 DOI: https://doi.org/10.1007/s10549-020-05941-7

Breast cancer diagnosed during pregnancy or lactation up to 1 year post-partum is often referred to as pregnancy-associated breast cancer (PABC), although the definition varies with length of post-partum period. The incidence rate has been reported to range from 17.5 to 39.9 per 100,000 births, but the rate is substantially lower during pregnancy (ranging from 3.0 to 7.7) than during the post-partum period (ranging from 13.8 to 32.2). The PABC incidence rate is increasing in many populations, and higher maternal age at birth is a likely explanation. Linkable population-based data on pregnancies and cancer are required to obtain reliable estimates of PABC incidence. In studies comparing outcomes in women with PABC to other young breast cancer patients, it is crucial to adjust for age, since the age distribution of PABC depends both on age at pregnancy and age at breast cancer. Large studies have shown similar prognosis for women with PABC compared to other young women with breast cancer, when accounting for differences in age, stage and other tumour characteristics.

Age and tumor subtype are prognostic factors for breast cancer survival, but it is unclear which matters the most. We used population-based data to address this question. We identified 21,384 women diagnosed with breast cancer at ages 20-89 between 2005 and 2015 in the Cancer Registry of Norway. Subtype was defined using estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2) status as luminal A-like (ER+PR+HER2-), luminal B-like HER2-negative (ER+PR-HER2-), luminal B-like HER2-positive (ER+PR+/-HER2+), HER2-positive (ER-PR-HER2+) and triple-negative (TNBC) (ER-PR-HER2-). Cox regression estimated hazard ratios (HR) for breast cancer-specific 7-year survival by age and subtype, while adjusting for year, grade, TNM stage and treatment. Young women more often had HER2-positive and TNBC tumors, while elderly women (70-89) more often had luminal A-like tumors. Compared to age 50-59, young women had doubled breast cancer-specific mortality rate (HR = 2.26, 95% CI 1.81-2.82), while elderly had two to five times higher mortality rate (70-79: HR = 2.25, 1.87-2.71; 80-89: HR = 5.19, 4.21-6.41). After adjustments, the association was non-significant among young women but remained high among elderly. Young age was associated with increased breast cancer-specific mortality among luminal A-like subtype, while old age was associated with increased mortality in all subtypes. Age and subtype were strong independent prognostic factors. The elderly always did worse, also after adjustment for subtype. Tumor-associated factors (subtype, grade and stage) largely explained the higher breast cancer-specific mortality among young. Future studies should address why luminal A-like subtype is associated with a higher mortality rate in young women.

Purpose With excellent cure rates for young patients with Hodgkin lymphoma (HL), there is an increasing number of female survivors of HL interested in becoming pregnant. Here, we report childbearing among contemporarily treated HL survivors in comparison with the general population. Material and Methods Using Swedish registers, 449 women (ages 18 to 40 years) diagnosed with HL between 1992 and 2009 and in remission 9 months after diagnosis were identified. Patients were age- and calendar-year–matched to 2,210 population comparators. Rates of first postdiagnosis childbirth were calculated. Hazard ratios (HRs) with 95% CIs were estimated for different follow-up periods using Cox regression. Cumulative probabilities of first childbirth were calculated in the presence of the competing risk of death or relapse. Results Twenty-two percent of relapse-free patients with HL had a child during follow-up, and first childbirth rates increased over time, from 40.2 per 1,000 person-years (1992 to 1997) to 69.7 per 1,000 person-years (2004 to 2009). For comparators, childbirth rates remained stable (70.1 per 1,000 person-years). Patients diagnosed between 2004 and 2009 had a cumulative probability of childbirth similar to comparators. Three years or more after diagnosis, no differences in childbirth rates were observed between patients and comparators, regardless of stage or treatment. Patients who received six to eight courses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone had a lower childbirth rate than comparators during the first 3 years (HR, 0.23; 95% CI, 0.06 to 0.94), as did patients who received six to eight courses of chemotherapy and radiotherapy (HR, 0.21; 95% CI, 0.07 to 0.65). Conclusion Childbearing potential among female survivors of HL has improved over time, and childbirth rates 3 years after diagnosis in contemporarily treated patients are, in the absence of relapse, similar to those in the general population, regardless of stage and treatment.

Background: Volumetric mammographic density (VMD) measures can be obtained automatically, but it is not clear how these relate to breast cancer risk factors. Methods: The cohort consisted of 46,428 women (ages 49–71 years) who participated in BreastScreen Norway between 2007 and 2014 and had information on VMD and breast cancer risk factors. We estimated means of percent and absolute VMD associated with age, menopausal status, body mass index (BMI), and other factors. Results: The associations between VMD and most breast cancer risk factors were modest, although highly significant. BMI was positively associated with absolute VMD, whereas inversely associated with percent VMD. Percent VMD was inversely associated with a 5-year older age at screening in premenopausal and postmenopausal women (−0.18% vs. −0.08% for percent VMD and −0.11 cm3 vs. −0.03 cm3 for absolute VMD). This difference was largest among postmenopausal women with BMI < 25 kg/m2 (P for interaction with percent VMD < 0.0001), never users of postmenopausal hormone therapy (P for interaction < 0.0001), and premenopausal women with a family history of breast cancer (P for interaction with absolute VMD = 0.054). Conclusions: VMD is associated with several breast cancer risk factors, the strongest being BMI, where the direction of the association differs for percent and absolute VMD. The inverse association with age appears modified by menopausal status and other breast cancer risk factors. Impact: Because VMD methods are becoming widely available in screening and clinical settings, the association between VMD measures and breast cancer risk factors should be investigated further in longitudinal studies. Cancer Epidemiol Biomarkers Prev; 27(9); 1065–74. ©2018 AACR.

Introduction Women undergoing fertility treatment experience high levels of stress. However, it remains uncertain if and how stress influences in vitro fertilization (IVF) cycle outcome. This study aimed to investigate whether self-reported perceived and infertility-related stress and cortisol levels were associated with IVF cycle outcomes. Material and methods A prospective cohort of 485 women receiving fertility treatment was recruited from September 2011 to December 2013 and followed until December 2014. Data were collected by online questionnaire prior to IVF start and from clinical charts. Salivary cortisol levels were measured. Associations between stress and cycle outcomes (clinical pregnancy and indicators of oocyte and embryo quality) were measured by logistic or linear regression, adjusted for age, body mass index, education, smoking, alcohol and caffeine consumption, shiftwork and night work. Results Ultrasound verified pregnancy rate was 26.6% overall per cycle started and 32.9% per embryo transfer. Stress measures were not associated with clinical pregnancy: when compared with the lowest categories, the adjusted odds ratio (OR) and 95% confidence interval (CI) for the highest categories of the perceived stress score was 1.04 (95% CI 0.58-1.87), infertility-related stress score was OR = 1.18 (95% CI 0.56-2.47), morning and evening cortisol was OR = 1.18 (95% CI 0.60-2.29) and OR = 0.66 (95% CI 0.34-1.30), respectively. Conclusions Perceived stress, infertility-related stress, and cortisol levels were not associated with IVF cycle outcomes. These findings are potentially reassuring to women undergoing fertility treatment with concerns about the influence of stress on their treatment outcome.

There is evidence of poor prognosis in women with pregnancy-associated breast cancer (PABC) diagnosed during pregnancy or within 2 years of delivery. Using a large, population-based cohort, we examined clinicopathologic features and survival in women with PABC. A cohort of women diagnosed with invasive breast cancer between 1992 and 2009 at ages 15-44 years was identified in the Swedish Cancer Register and the Breast Cancer Quality Registers. Dates of childbirths for each woman were retrieved from the Swedish Multi-Generation Register. Age-standardized distributions of tumor stage (tumor size, nodal status, metastasis), Elston grade and ER/PR/HER2 status were compared between nulliparous women and women with breast cancer during pregnancy and up to 10 years postdelivery. Adjusted hazard ratios for all-cause mortality rates among patients were estimated using Cox regression. We identified 1,661 nulliparous women with breast cancer, 778 women with PABC (97 during pregnancy, 270 within first and 411 within second year postdelivery) and 3,598 during 2-10 years postdelivery. Compared to nulliparous women, women with PABC, and especially women diagnosed 0-12 months after delivery, had more advanced T and N stage, and higher proportions of ER/PR negative, HER2 positive and triple-negative tumors. Increased hazard ratios were observed in women diagnosed within 5 years of delivery after adjustment for age, year, education and region. Following additional adjustment for tumor characteristics, the hazard ratios were attenuated and nonsignificant. The poorer prognosis observed in women with PABC appears to be largely explained by more adverse tumor characteristics at diagnosis.

Background While urinary bladder cancer is consistently more common in men worldwide, women have poorer prognosis. The aim of this study was to outline sex differences in prognostic factors and clinical management and to explore whether these can explain the poorer urinary bladder cancer outcome in women. Patients and Methods We performed a population-based cohort study including all patients diagnosed with urothelial bladder cancer between 1997 and 2014 at age 18 to 89 who had data recorded in the Swedish Urinary Bladder Cancer Register (n = 36,344). Female-to-male odds ratios for clinical management parameters were estimated by logistic regression. To quantify sex differences in bladder cancer–specific survival, we estimated empirical survival proportions and mortality rates as well as applied flexible parametric models to estimate female-to-male hazard ratios and survival proportions over follow-up. Adjusted models included age, year, World Health Organization grade, stage, marital status, education, health care region, birth country, and comorbidity. Results Except for an adverse stage distribution in women, we found no evidence of unequal clinical management. Among those diagnosed with bladder cancer, women had a higher bladder cancer mortality (adjusted hazard ratio, 1.15; 95% confidence interval, 1.08-1.23) driven by muscle-invasive tumors (adjusted hazard ratio, 1.24; 95% confidence interval, 1.14-1.34). The female survival disadvantage was confined to the first 2 years after diagnosis. Conclusion The excess bladder cancer mortality in women is limited to those diagnosed with muscle-invasive tumors and cannot be explained by the examined clinicopathologic factors. Further investigations of sex differences in therapeutic procedures and outcomes, including complications, of muscle-invasive bladder cancer, must be performed.

Amelogenesis imperfecta (AI) is a hereditary developmental disorder affecting the enamel of teeth. Affected patients present with tooth hypersensitivity, rapid tooth wear, or fractures of enamel as well as alterations in color and shape, all of which compromise esthetic appearance and masticatory function. Chronic conditions in childhood severely impact the whole family, affecting normal family routines and/or increasing the family&rsquo, s financial burden. The aim of this study was to explore experiences and the impact on daily life of being a parent to a child with severe forms of amelogenesis imperfecta. Parents of children and adolescents with AI participated in an interview with a psychologist. The transcribed interviews were analyzed using thematic analysis. The parents talked about several concerns about having a child with AI. Four main themes emerged from the interviews: Feelings associated with passing on a hereditary disorder, knowledge decreases stress, unfamiliarity with the diagnosis, and psychosocial stress. In these main categories we identified several subthemes. Feelings associated with passing on a hereditary disorder included the subtheme of guilt/shame, knowledge decreases stress included knowledge about diagnosis in the family and support from dental health care professionals, Unfamiliarity with diagnosis included missed diagnosis, fear of not getting correct treatment, and insufficient pain control, finally, the subtheme Psychosocial stress included fear of child being bullied and emergency dental visits. The findings show that parents of children with severe amelogenesis imperfecta report similar experiences as do parents of children with other chronic and rare diseases.

Background Despite advances in life expectancy, low socioeconomic status is associated with a shorter lifespan. This study was conducted to investigate socioeconomic differences in mortality by comparing preventable with non-preventable causes of death in 39 506 participants from the Swedish Twin Registry born before 1935. Methods Childhood social class, own education, own social class and social mobility were used as separate indicators of socioeconomic status. These data were linked to the Swedish Cause of Death Register. Cause of death was categorized as preventable or non-preventable mortality according to indicators presented in the Avoidable Mortality in the European Union (AMIEHS) atlas. Using Cox proportional hazard models, we tested the association between the socioeconomic measures and all-cause mortality, preventable mortality and non-preventable mortality. Additional co-twin control analyses indicated whether the associations reflected genetic confounding. Results The social gradient for mortality was most prominent for the adult socioeconomic measures. There was a social gradient in both preventable mortality and non-preventable mortality, but with an indication of a moderately stronger effect in preventable causes of death. In analyses of social mobility, those who experienced life-time low socioeconomic status (SES) or downward social mobility had an increased mortality risk compared with those with life-time high SES and upward social mobility. Adjustments for genetic confounding did not change the observed associations for education, social class or social mobility and mortality. In the co-twin control analyses of reared-apart twins, the association between childhood social class and mortality weakened, indicating possible genetic influences on this association. Conclusions Our results indicate that there is an association between low adult socioeconomic status and increased mortality independent of genetic endowment. Thus, we do not find support for indirect social selection as the basis for mortality inequalities in Sweden

Despite concerns about the mental health of breast cancer patients, little is known regarding the temporal risk pattern and risk factors of common mental disorders among these patients. We estimated standardized incidence ratios (SIRs) of depression, anxiety and stress-related disorders in a Swedish nationwide cohort of 40,849 women with invasive and 4,402 women with in situ breast cancer (2001–2010, median follow-up = 4.5 years). The impact of patient, tumor and treatment characteristics was analyzed using flexible parametric survival models in a regional cohort of 7,940 invasive breast cancer patients (2001–2013, median follow-up = 7.5 years). Women with invasive breast cancer showed increased rates of depression, anxiety and stress-related disorders [overall SIR (95% CI) = 1.57 (1.46–1.69), 1.55 (1.43–1.68) and 1.77 (1.60-1.95), respectively]. SIRs were highest shortly after diagnosis, but remained increased up to 5 years. Younger age at diagnosis, comorbidity, higher-grade disease, lymph node involvement and chemotherapy were independently associated with the risk of depression and anxiety in invasive cancer patients, with chemotherapy and higher-grade disease conferring short-term risk only, while comorbidities were mainly associated with late-onset events. No clinical risk factors were identified for stress-related disorders except for a greater risk associated with younger age. Patients with in situ cancer only showed an increased incidence of stress-related disorders during the first 6 months after diagnosis [SIR (95% CI) = 2.76 (1.31-5.79)]. The time-dependent risk profile of invasive cancer patients may guide health care professionals for timely and targeted psycho-oncologic interventions.

Purpose: Venous thromboembolism (VTE) is highly heritable and a serious complication of cancer and its treatment. We examined the individual and joint effects of chemotherapy and genetic susceptibility on VTE risk in patients with breast cancer. Experimental Design: A Swedish population-based study including 4,261 women diagnosed with primary invasive breast cancer between 2001 and 2008 in Stockholm, followed until 2012. Risk stratification by chemotherapy and genetic susceptibility [a polygenic risk score (PRS), including nine established VTE loci] was assessed using Kaplan–Meier and flexible parametric survival analyses, adjusting for patient, tumor, and treatment characteristics. Results: In total, 276 patients experienced a VTE event during a median follow-up of 7.6 years. Patients receiving chemotherapy [HR (95% CI) = 1.98; 1.40–2.80] and patients in the highest 5% of the PRS [HR (95% CI) = 1.90; 1.24–2.91] were at increased risk of developing VTE. Chemotherapy and PRS acted independently on VTE risk and the 1-year cumulative incidence in patients carrying both risk factors was 9.5% compared with 1.3% in patients not having these risk factors (P < 0.001). Stratified analyses by age showed that the risk-increasing effect of PRS was stronger in older patients (P interaction = 0.04), resulting in an excess risk among genetically susceptible patients receiving chemotherapy aged ≥ 60 years (1-year cumulative incidence = 25.0%). Conclusions: Risk stratification by chemotherapy and genetic susceptibility identifies patients with breast cancer at high VTE risk, who could potentially benefit from thromboprophylaxis. Our results further suggest that genetic testing is more informative in older patients with breast cancer. Clin Cancer Res; 22(21); 5249–55. ©2016 AACR.

Background: Bone fractures may have an impact on prognosis of breast cancer. The long-term risks of bone fracture in breast cancer patients have not been thoroughly studied. Methods: Poisson regression was used to investigate the incidence of hospitalisation due to bone fracture comparing women with and without breast cancer based on Swedish National registers. Cox regression was used to investigate the risk of being hospitalised with bone fracture, and subsequent risk of death, in a regional cohort of breast cancer patients. Results: For breast cancer patients, the 5-year risk of bone fracture hospitalisation was 4.8% and the 30-day risk of death following a bone fracture hospitalisation was 2.0%. Compared with the general population, breast cancer patients had incidence rate ratios of 1.25 (95% CI: 1.23–1.28) and 1.18 (95% CI: 1.14–1.22) for hospitalisation due to any bone fracture and hip fracture, respectively. These ratios remained significantly increased for 10 years. Comorbidities (Charlson Comorbidity Index ⩾1) were associated with the risk of being hospitalised with bone fracture. Women taking aromatase inhibitors were at an increased risk as compared with women taking tamoxifen (HR=1.48; 95% CI: 0.98–2.22). Breast cancer patients hospitalised for a bone fracture showed a higher risk of death (HR=1.83; 95% CI: 1.50–2.22) compared with those without bone fracture. Conclusions: Women with a previous breast cancer diagnosis are at an increased risk of hospitalisation due to a bone fracture, particularly if they have other comorbidities.

Background: While research has shown that sleep disorders are prevalent among people with dementia, the temporal relationship is unclear. We investigated whether atypical sleep characteristics were associated with incident dementia while accounting for baseline cognitive functioning. Methods: Screening Across the Lifespan Twin Study (SALT) participants were 11,247 individuals from the Swedish Twin Registry who were at least 65 years at baseline (1998-2002). Sleep and baseline cognitive functioning were assessed via the SALT telephone screening interview. Data on dementia diagnoses came from national health registers. Cox regression was performed to estimate hazard ratios (HR) for dementia. Results: After 17 years of follow-up, 1,850 dementia cases were identified. Short (≤ 6 hours) and extended (> 9 hours) time-in-bed (TIB) compared to the middle reference group (HR=1.40, 95% CI=1.06-1.85, HR=1.11, 95% CI=1.00-1.24, respectively) and rising at 8:00AM or later compared to earlier rising (HR=1.12, 95% CI=1.01-1.24) were associated with higher dementia incidence. Bedtime, sleep quality, restorative sleep, and heavy snoring were not significant predictors. Findings stratified by baseline cognitive status indicated that the association between short TIB and dementia remained in those cognitively intact at the start. Conclusions: Short and extended TIB as well as delayed rising among older adults predicted increased dementia incidence in the following 17 years. The pattern of findings suggests that extended TIB and late rising represent prodromal features whereas short TIB appeared to be a risk factor for dementia. This work was supported by grants from the National Institute on Aging (R01-AG08724) and the Swedish Research Council for Health, Working Life and Welfare (FORTE).

Summary Objectives Infections are a common cause of hospitalization in breast cancer patients. We studied the risk, clinical characteristics and outcomes of infection-related hospitalizations in this patient population. Methods A Swedish registry-based study including 8338 breast cancer patients diagnosed between 2001 and 2008, followed prospectively for infection-related hospitalizations until 2010. Standardized incidence ratios (SIRs) were calculated using background rates from the general female population. Associations with clinical characteristics and mortality were analyzed using flexible parametric survival models. Results In total, 720 patients experienced an infection-related hospitalization during a median follow-up of 4.9 years. Infection rates were highest within the first year of diagnosis (SIR = 5.61, 95% CI; 4.98–6.32), and site-specific risks were most pronounced for sepsis (SIR = 3.14, 95% CI; 2.66–3.71) and skin infections (SIR = 2.80, 95% CI; 2.24–3.50). Older age at diagnosis, comorbidities, markers of tumor aggressiveness, chemotherapy and axillary node dissection were independent predictors of infectious disease risk. Infection-related hospitalizations were also independently associated with overall and breast cancer-specific death. Conclusions A significant number of breast cancer patients are hospitalized with an infection following diagnosis, which in turn predicts poor prognosis. The risk profile of infection-related hospitalizations is multifactorial, including patient, tumor and treatment-related factors.

Background: Infection-related hospitalizations are a serious complication in breast cancer patients, resulting in treatment delay, prolonged hospitalization and future morbidity and mortality. Little, however, is known about the actual risk, clinical characteristics and outcomes of infection-related hospitalizations in this patient population. Methods: We conducted a prospective population-based study including 7071 women diagnosed with primary invasive non-metastatic breast cancer between 2001 and 2008 in the Stockholm-Gotland region (Sweden), with complete follow-up until 2010. Standardized incidence ratios (SIRs) for infection-related hospitalizations (overall and by site) were estimated using background rates from the general female population, matched on age and calendar period. Associations with clinical characteristics and breast cancer outcomes (breast cancer death, distant metastasis and locoregional recurrence) were analysed using flexible parametric survival models. Results: During a medium follow-up of 5.3 years, 657 hospital admissions with infections were observed and 1,2 and 5-year cumulative risks were 3.4, 4.7 and 8.1% respectively. Rates of infection-related hospitalizations were increased compared to the general female population (SIR = 2.12; 95% CI = 1.96-2.29) and site-specific SIRs were most pronounced for sepsis (SIR = 3.65; 95% CI = 3.13-4.26) and skin infections (SIR = 2.93; 95% CI = 2.35-3.64). The overall risk of infections was highest during the first year (SIR = 5.06; 95% CI, 4.46-5.74), and recurrent disease contributed to the long-term risk observed. Older age at diagnosis, chemotherapy, axillary radiotherapy, comorbidities and markers of tumor aggressiveness (large tumors, estrogen receptor negative tumors and lymph node positive tumors) were independent predictors of infectious disease risk. Analyses evaluating the prognostic impact of infections revealed an independent effect on breast cancer death and distant metastasis, associations that were mainly driven by sepsis (HR = 4.53; 95% CI, 3.25-6.33 and 1.69; 95% CI, 1.04-2.79 respectively). No association was found with future risk of locoregional recurrence. Conclusions: Physicians and patients should be aware of the risk of serious infections which persists beyond the initial treatment period. Infection-related hospitalizations are an independent marker of poor prognosis. Further research is needed to elucidate the role of sepsis in breast cancer progression. Citation Format: Brand JS, Colzani E, Johansson A, Giesecke J, Clements M, Bergh J, Hall P, Czene K. Infectious disease hospitalization in breast cancer patients: Risk and impact on prognosis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-07-22.

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. Results 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). Conclusion 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.

BACKGROUND The purpose of this study was to assess patterns of cancer occurrence during pregnancy and the postpartum period. METHODS This was a register-based study using data from the Swedish Multi-Generation Register and the National Cancer Register from 1963 to 2007. Pregnancy-associated cancer (PAC) was defined as a malignancy detected during pregnancy or within 2 years of delivery and was assessed in 7 time windows: pregnancy, trimesters 1-3, 0-6 months, 7-12 months, and second year postpartum. Population incidence rates by 5-year age groups and periods were used to estimate the expected number of PACs for each site. The observed versus the expected (O/E) number of cases was estimated with 95% confidence intervals (CI). RESULTS The 3 most common malignancies during pregnancy were melanoma (n = 232), breast (n = 139) and cervical cancer (n = 139). With a slightly different rank order, these cancers are also the most common in women of childbearing age. The number of observed cases during pregnancy was lower than expected for all cancers, with a combined O/E ratio for all sites of 0.46 (95% CI, 0.43-0.49). The O/E ratio was close to 1 during all postpartum intervals, including 0-6 months (0.93; 95% CI, 0.88-0.98), 7-12 months (0.96; 95% CI, 0.91-1.01), and during the second year after delivery (0.95; 95% CI, 0.92-0.99). CONCLUSIONS The rate of cancer during pregnancy was lower than expected for all sites, a finding that could not be explained entirely by delayed diagnosis. A rebound in the number of observed cases after delivery was restricted to melanoma, nervous system malignancies, and breast and thyroid cancer. Cancer 2015;121:2072–2077. © 2015 American Cancer Society.

Background & Aims Proton pump inhibitors (PPI) have been associated with acute kidney injury and recent studies suggest that they may be associated with the risk of chronic kidney disease (CKD). Methods We performed a retrospective analysis using the Stockholm creatinine measurements database, which contains information on diagnoses, dispensation claims, and laboratory test results for all citizens in the Stockholm region from 2007 through 2010. We identified new users of PPIs (n = 105,305) and new users of H 2 blockers (H 2 B; n = 9578); data on renal outcomes were collected for a median 2.7 years. The primary outcome was progression CKD, defined as doubling of creatinine or decrease in estimated glomerular filtration rate of 30% or more. Secondary outcomes were end-stage renal disease and acute kidney injury. Complete collection of repeated PPI and H 2 B dispensations at pharmacies in Sweden allowed modeling the time-dependent risk associated with cumulative PPI exposure. Results Users of PPIs, compared with users of H 2 Bs, had an increased risk for doubled levels of creatinine (1985 events; adjusted hazard ratio [HR], 1.26; 95% CI, 1.05–1.51) and decrease in estimated glomerular filtration rate of 30% or more (11,045 events; 1.26; 95% CI, 1.16–1.36). PPI use also associated with development of end-stage renal disease (HR, 2.40; 95% CI, 0.76–7.58) and acute kidney injury (HR, 1.30; 95% CI, 1.00–1.69). There was a graded association between cumulative exposure to PPIs and risk of CKD progression. This was not the case for cumulative H 2 B use. Conclusions Initiation of PPI therapy and cumulative PPI exposure is associate with increased risk of CKD progression in a large, North European healthcare system. Although consistent, the association was modest in magnitude, and cannot exclude residual confounding.

Quantitative knowledge of the long-term human papillomavirus (HPV) type-specific risks for high-grade cervical intraepithelial neoplasias Grades 2 and 3 (CIN2 and CIN3) is useful for estimating the effect of elimination of specific HPV types and clinical benefits of screening for specific HPV types. We estimated HPV type-specific risks for CIN2 and CIN3 using a randomized primary HPV screening trial followed up for 14.6 years using comprehensive, nationwide registers. Poisson regression estimated cumulative incidences, population attributable proportions (PAR) and incidence rate ratios (IRRs) of high-grade lesions by baseline HPV type, with censoring at date of first CIN2/3 or last registered cytology. Multivariate analysis adjusted for coinfections. IRRs were highest during the first screening round, but continued to be high throughout follow-up (IRRs for CIN3 associated with high-risk (HR) HPV positivity were 226.9, 49.3, 17.7 and 10.3 during the first, second and third screening round and for >9 years of follow-up, respectively). Increased long-term risks were found particularly for HPV Types 16, 18 and 31 and for CIN3+ risks. HPV16/18/31/33 had 14-year cumulative incidences for CIN3+ above 28%, HPV35/45/52/58 had 14 year risks between 14% and 18% and HPV39/51/56/59/66/68 had risks

Human papillomavirus (HPV) infections result in a significant burden of low-grade cervical lesions. Between 1997 and 2000, our randomized trial of primary HPV screening enrolled 12,527 women participating in population-based screening. Women between 32 and 38 years of age (median: 34, interquartile range: 33-37) were randomized to HPV and cytology double testing (intervention arm, n = 6,257 enrolled, n = 5,888 followed-up) or to cytology, with samples frozen for future HPV testing (control arm, n = 6,270 enrolled, n = 5,795 followed-up). We estimated the HPV type-specific, long-term absolute risks (AR), and population attributable proportions (PAR) for cytological diagnoses of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) and for histopathologically diagnosed cervical intraepithelial neoplasia grade 1 (CIN1). The women were followed using comprehensive, nationwide register-based follow-up. During a mean follow-up time of 11.07 years, 886 ASCUS and LSIL lesions were detected, 448 in the intervention arm and 438 in the control arm. Poisson regression estimated the incidence rate ratios (IRRs) of low-grade lesions by HPV type. The IRRs were strongly dependent on follow-up time. The IRRs for ASCUS/LSIL associated with high-risk HPV positivity were 18.6 (95% CI: 14.9-23.4) during the first screening round, 4.1 (95% CI: 2.8-6.2) during the second, 2.6 (95% CI: 1.7-4.1) during the third, and 1.1 (95% CI: 0.7-1.8) for >9 years of follow-up, with similar declines seen for the individual types. Type 16 contributed consistently to the greatest proportion of ASCUS, LSIL, and CIN1 risk in the population (first screening round PAR: ASCUS: 15.5% (95% CI: 9.7-21.9), LSIL: 14.7% (95% CI: 8.0-20.9), and CIN1: 13.4% (95% CI: 3.2-22.5)), followed by type 31 [8.4% (95% CI: 4.2-12.5) for ASCUS to 17.3% (95% CI: 6.8-26.6) for CIN1]. In summary, most ASCUS/LSIL lesions associated with HPV infection are caused by new HPV infections and most lesions are found during the first screening round.