Menopausal hormone therapy and breast cancer risk: a population-based cohort study of 1.3 million women in Norway.

BACKGROUND: It is important to monitor the association between menopausal hormone therapy (HT) use and breast cancer (BC) risk with contemporary estimates, and specifically focus on HT types and new drugs. METHODS: We estimated hazard ratios (HR) of BC risk according to HT type, administration route and individual drugs, overall and stratified by body mass index (BMI), molecular subtype and detection mode, with non-HT use as reference. RESULTS: We included 1,275,783 women, 45+ years, followed from 2004, for a median of 12.7 years. Oral oestrogen combined with daily progestin was associated with the highest risk of BC (HR 2.42, 95% confidence interval (CI) 2.31-2.54), with drug-specific HRs ranging from Cliovelle®: 1.63 (95% CI 1.35-1.96) to Kliogest®: 2.67 (2.37-3.00). Vaginal oestradiol was not associated with BC risk. HT use was more strongly associated with luminal A cancer (HR 1.97, 95% CI 1.86-2.09) than other molecular subtypes, and more strongly with interval (HR 2.00, 95% CI: 1.83-2.30) than screen-detected (HR 1.33, 95% CI 1.26-1.41) BC in women 50-71 years. HRs for HT use decreased with increasing BMI. CONCLUSIONS: The use of oral and transdermal HT was associated with an increased risk of BC. The associations varied according to HT type, individual drugs, molecular subtype, detection mode and BMI.

How Did Breast Cancer Patients Fare during Different Phases of the COVID-19 Pandemic in Norway Compared to Age-Matched Controls?

Little is known about how health-related quality of life (HRQoL) in breast cancer cases differed from that of controls during and after the COVID-19 pandemic. This study used data from an ongoing, nationwide HRQoL survey of 4279 newly diagnosed breast cancer cases and 2911 controls to investigate how breast cancer patients fared during different phases of the pandemic compared to controls. Responders during 2020-2022 were categorized into three COVID-19-related phases: the social restrictions phase, the high infection rate phase, and the post-pandemic phase. Across phases, breast cancer cases had significantly worse scores in most HRQoL domains compared to controls. Apart from slightly more insomnia in the high infection rate phase for both cases and controls, and better social functioning for young cases in the post-COVID-19 phase, the case-control differences in HRQoL remained consistent across phases. When the phases were assessed as one period, young women and those living with children <18 years of age fared the worst among breast cancer cases, while single women fared the worst among controls. In contrast, controls living with children <18 years of age exhibited better HRQoL than controls without children. In summary, women with breast cancer did not appear to fare differently than controls in terms of HRQoL across COVID-19 phases. However, breast cancer cases with young children fared worse in their HRQoL than other breast cancer cases.

Cumulative incidence of second primary cancers in a large nationwide cohort of Danish cancer survivors: a population-based retrospective cohort study.

BACKGROUND: A new primary cancer is a serious late effect of a pre-existing cancer diagnosis, and can be attributed to hereditary cancer syndromes, immune or hormonal factors, cancer treatment, or modifiable lifestyle or environmental factors. We investigated the absolute and relative incidence of second primary cancers in a large cohort of Danish cancer survivors. Furthermore, we examined the association between alcohol-related, smoking-related, virus-related, and hormone-related first and second primary cancers. METHODS: In this retrospective cohort study, we identified a cohort of Danish adults (aged ≥40 years) diagnosed with cancer from Jan 1, 1997, to Dec 31, 2014 and alive 1 year after diagnosis. Follow-up was from date of first cancer diagnosis and lasted up to 24 years, ending on Dec 31, 2020. Cohort identification and information on second primary cancers was obtained from the Danish Cancer Registry, and comorbidity and sociodemographic information was obtained from Danish population-based registries. Overall, and for 27 cancer types, cumulative incidence functions and Cox proportional hazard regression models were used to estimate the incidence of second primary cancer and death, and hazard ratios (HRs) and 95% CIs of second primary cancer adjusted for sex, age and year of diagnosis, cohabitation status, income, and comorbidity. FINDINGS: 457 334 Danish adults were included in our study (230 150 [50·3%] male individuals and 227 184 [49·7%] female individuals; median age at diagnosis 68·3 years, IQR 59·7-76·6; median follow-up 3·6 years, IQR 0·6-9·3). The cumulative incidence of second primary cancer increased over time from 6·3% (95% CI 6·2-6·4) 5 years after diagnosis to 10·5% (10·4-10·6) 10 years after diagnosis and to 13·5% (13·4-13·7) 15 years after diagnosis. The highest cumulative incidence of second primary cancer 10 years after diagnosis was observed in survivors of cancers in the larynx (21·8%, 20·5-23·1), oropharynx and oral cavity (19·5%, 18·7-20·3), and bladder and urinary tract (18·5%, 18·0-19·0). Survivors of cancers related to alcohol (HR 1·09, 95% CI 1·06-1·13), smoking (1·73, 1·68-1·78), diet high in red or processed meat (1·32, 1·24-1·39), or virus (1·23, 1·13-1·35) were at increased risk of developing a second cancer with the same aetiology, whereas having had a hormone-related first cancer was associated with lower risk of a second hormone-related cancer (0·77, 0·73-0·81). INTERPRETATION: Our results could help optimise prevention efforts targeting modifiable risk factors to reduce risk of developing a second primary cancer. FUNDING: Nordic Cancer Union and The Health Foundation (Helsefonden).

Trajectories of body mass index in adulthood and risk of subtypes of postmenopausal breast cancer.

BACKGROUND: Body fatness is a dynamic exposure throughout life. To provide more insight into the association between body mass index (BMI) and postmenopausal breast cancer, we aimed to examine the age at onset, duration, intensity, and trajectories of body fatness in adulthood in relation to risk of breast cancer subtypes. METHODS: Based on self-reported anthropometry in the prospective Norwegian Women and Cancer Study, we calculated the age at onset, duration, and intensity of overweight and obesity using linear mixed-effects models. BMI trajectories in adulthood were modeled using group-based trajectory modeling. We used Cox proportional hazards models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the associations between BMI exposures and breast cancer subtypes in 148,866 postmenopausal women. RESULTS: A total of 7223 incident invasive postmenopausal breast cancer cases occurred during follow-up. Increased overweight duration and age at the onset of overweight or obesity were associated with luminal A-like breast cancer. Significant heterogeneity was observed in the association between age at overweight and overweight duration and the intrinsic-like subtypes (pheterogeneity 0.03). Compared with women who remained at normal weight throughout adulthood, women with a descending BMI trajectory had a reduced risk of luminal A-like breast cancer (HR 0.54, 95% CI 0.33-0.90), whereas women with ascending BMI trajectories were at increased risk (HR 1.09; 95% CI 1.01-1.17 for "Normal-overweight"; HR 1.20; 95% CI 1.07-1.33 for "Normal-obesity"). Overweight duration and weighted cumulative years of overweight and obesity were inversely associated with luminal B-like breast cancer. CONCLUSIONS: In this exploratory analysis, decreasing body fatness from obesity in adulthood was inversely associated with overall, hormone receptor-positive and luminal A-like breast cancer in postmenopausal women. This study highlights the potential health benefits of reducing weight in adulthood and the health risks associated with increasing weight throughout adult life. Moreover, our data provide evidence of intrinsic-like tumor heterogeneity with regard to age at onset and duration of overweight.

Digital Cognitive Behavioral- and Mindfulness-Based Stress-Management Interventions for Survivors of Breast Cancer: Development Study.

BACKGROUND: Psychosocial stress-management interventions can reduce stress and distress and improve the quality of life for survivors of cancer. As these in-person interventions are not always offered or accessible, evidence-informed digital stress-management interventions may have the potential to improve outreach of psychosocial support for survivors of cancer. Few such digital interventions exist so far, few if any have been developed specifically for survivors of breast cancer, and few if any have attempted to explore more than 1 distinct type of intervention framework. OBJECTIVE: This study aimed to develop 2 digital psychosocial stress-management interventions for survivors of breast cancer; 1 cognitive behavioral therapy-based intervention (CBI), and 1 mindfulness-based intervention (MBI). METHODS: The development of the CBI and MBI interventions originated from the existing StressProffen program, a digital stress-management intervention program for survivors of cancer, based on a primarily cognitive behavioral therapeutic concept. Development processes entailed a multidisciplinary design approach and were iteratively conducted in close collaboration between key stakeholders, including experts within psychosocial oncology, cancer epidemiology, stress-management, and eHealth as well as survivors of breast cancer and health care providers. Core psychosocial oncology stress-management and cancer epidemiology experts first conducted a series of workshops to identify cognitive behavioral and mindfulness specific StressProffen content, overlapping psychoeducational content, and areas where development and incorporation of new material were needed. Following the program content adaptation and development phase, phases related to user testing of new content and technical, privacy, security, and ethical aspects and adjustments ensued. Intervention content for the distinct CBI and MBI interventions was refined in iterative user-centered design processes and adjusted to electronic format through stakeholder-centered iterations. RESULTS: For the CBI version, the mindfulness-based content of the original StressProffen was removed, and for the MBI version, cognitive behavioral content was removed. Varying degrees of new content were created for both versions, using a similar layout as for the original StressProffen program. New content and new exercises in particular were tested by survivors of breast cancer and a project-related editorial team, resulting in subsequent user centered adjustments, including ensuring auditory versions and adequate explanations before less intuitive sections. Other improvements included implementing a standard closing sentence to round off every exercise, and allowing participants to choose the length of some of the mindfulness exercises. A legal disclaimer and a description of data collection, user rights and study contact information were included to meet ethical, privacy, and security requirements. CONCLUSIONS: This study shows how theory specific (ie, CBI and MBI) digital stress-management interventions for survivors of breast cancer can be developed through extensive collaborations between key stakeholders, including scientists, health care providers, and survivors of breast cancer. Offering a variety of evidence-informed stress-management approaches may potentially increase interest for outreach and impact of psychosocial interventions for survivors of cancer. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/47195.

Prediagnostic Hormone Levels and Risk of Testicular Germ Cell Tumors: A Nested Case-Control Study in the Janus Serum Bank.

BACKGROUND: It has been hypothesized that poorly functioning Leydig and/or Sertoli cells of the testes, indicated by higher levels of serum gonadotropins and lower levels of androgens, are related to the development of testicular germ cell tumors (TGCT). To investigate this hypothesis, we conducted a nested case-control study within the Janus Serum Bank cohort. METHODS: Men who developed TGCT (n = 182) were matched to men who did not (n = 364). Sex steroid hormones were measured using LC/MS. Sex hormone binding globulin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were quantified by direct immunoassay. Multivariable logistic regression was used to calculate ORs and 95% confidence intervals (CI) for associations between hormone levels and TGCT risk. RESULTS: Higher FSH levels [tertile (T) 3 vs. T2: OR = 2.89, 95% CI = 1.83-4.57] were associated with TGCT risk, but higher LH levels were not (OR = 1.26, 95% CI = 0.81-1.96). The only sex steroid hormone associated with risk was androstane-3α, 17ß-diol-3G (3α-diol-3G; OR = 2.37, 95% CI = 1.46-3.83). Analysis by histology found that increased FSH levels were related to seminoma (OR = 3.55, 95% CI = 2.12-5.95) but not nonseminoma (OR = 1.19, 95% CI = 0.38-3.13). Increased levels of 3α-diol-3G were related to seminoma (OR = 2.29, 95% CI = 1.35-3.89) and nonsignificantly related to nonseminoma (OR = 2.71, 95% CI = 0.82-8.92). CONCLUSIONS: Higher FSH levels are consistent with the hypothesis that poorly functioning Sertoli cells are related to the development of TGCT. In contrast, higher levels of 3α-diol-3G do not support the hypothesis that insufficient androgenicity is related to risk of TGCT. IMPACT: Clarifying the role of sex hormones in the development of TGCT may stimulate new research hypotheses.

Were cancer patients worse off than the general population during the COVID-19 pandemic? A population-based study from Norway, Denmark and Iceland during the pre-vaccination era.

Background: In a population-based setting, we investigated the risks of testing positive for SARS-CoV-2 and developing severe COVID-19 outcomes among cancer patients compared with the general population. Methods: In nationwide cohorts, we identified all individuals in Norway, Denmark and Iceland who tested positive for SARS-CoV-2 or had a severe COVID-19 outcome (hospitalisation, intensive care, and death) from March until December 2020, using data from national health registries. We estimated standardised incidence ratios (SIRs) with 95% confidence intervals (CIs) comparing cancer patients with the general population. Findings: During the first wave of the pandemic, cancer patients in Norway and Denmark had higher risks of testing SARS-CoV-2 positive compared to the general population. Throughout 2020, recently treated cancer patients were more likely to test SARS-CoV-2 positive. In Iceland, cancer patients experienced no increased risk of testing positive. The risk of COVID-19-related hospitalisation was higher among cancer patients diagnosed within one year of hospitalisation (Norway: SIR = 2.43, 95% CI 1.89-3.09; Denmark: 2.23, 1.96-2.54) and within five years (Norway: 1.58, 1.35-1.83; Denmark: 1.54, 1.42-1.66). Risks were higher in recently treated cancer patients and in those diagnosed with haematologic malignancies, colorectal or lung cancer. Risks of COVID-19-related intensive care and death were higher among cancer patients. Interpretation: Cancer patients were at increased risk of testing positive for SARS-CoV-2 during the first pandemic wave when testing availability was limited, while relative risks of severe COVID-19 outcomes remained increased in cancer patients throughout 2020. Recent cancer treatment and haematologic malignancy were the strongest risk factors. Funding: Nordic Cancer Union.

Cervical, liver and stomach cancer incidence and mortality in non-Western immigrant women: a retrospective cohort study from four Nordic countries.

BACKGROUND: Cervical, liver and stomach cancers are the most common infection-associated malignancies and the leading cause of morbidity in non-Western regions. We compared the incidence and mortality of these cancers between non-Western immigrant and non-immigrant Nordic female populations. We also analysed the effect of age at immigration, duration of residence and education on cancer burden. MATERIAL AND METHODS: Study population consisted of women residents in Denmark, Finland, Iceland and Norway in 1973-2020. Non-Western women contributed 3.1% of the total 260 million person-years at risk. All women were followed from their 20th birthday, or from the date of immigration if after, until the date of their first primary cancer diagnosis, death, emigration, or the end of the country-specific study period. All data were adjusted for 10-year age groups and calendar periods, and immigrant data was further broken down by region of birth, age at immigration and education level. Country-specific estimates were produced by multivariable Poisson regression and pooled in Finland with a random effects model. RESULTS: Altogether, there were 60 982 cases of cervical, liver and stomach cancer in the study population, causing 36 582 deaths. The immigrant women had significantly higher liver (rate ratio [RR] 1.78, 95% confidence interval (CI) 1.03-3.06) and stomach cancer incidence (RR 1.68, CI 1.29-2.18), and stomach cancer mortality (RR 1.49, CI 1.17-1.92) than non-immigrant women. In the immigrant population, high education was related to lower incidence and mortality of studied cancers. The rate ratio of cervical cancer decreased with duration of residence and increased with rising age at immigration. CONCLUSION: Due to the increased incidence and mortality of infection-related cancers and changes in cancer patterns by age at immigration and duration of residence, attention should be paid to targeted health care services for immigrants. Special efforts should be given to women who have spent their youth in high-risk areas.

Low-dose aspirin, statins, and metformin and survival in patients with breast cancers: a Norwegian population-based cohort study.

BACKGROUND: Previous studies assessed the prognostic effect of aspirin, statins, and metformin in breast cancer (BC) patients, with inconclusive results. METHODS: We performed a nationwide population-based cohort study to evaluate if post-diagnostic use of low-dose aspirin, statins, and metformin was associated with BC-specific survival. Women aged ≥ 50 years and diagnosed with BC in 2004-2017, who survived ≥ 12 months after diagnosis (follow-up started 12 months after diagnosis), were identified in the Cancer Registry of Norway. The Norwegian Prescription Database provided information on prescriptions. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between post-diagnostic use and BC-specific survival, overall and by oestrogen receptor (ER) status. RESULTS: A total of 26,190 patients were included. Of these, 5324 (20%), 7591 (29%), and 1495 (6%) were post-diagnostic users of low-dose aspirin, statins, and metformin, respectively. The median follow-up was 6.1 years, and 2169 (8%) patients died from BC. HRs for use, compared to no use, were estimated at 0.96 (95% CI 0.85-1.08) for low-dose aspirin (ER+: HR = 0.97, 95% CI 0.83-1.13; ER-: HR = 0.97, 95% CI 0.73-1.29, p value for interaction = 0.562), 0.84 (95% CI 0.75-0.94) for statins (ER+: HR = 0.95, 95% CI 0.82-1.09; ER-: HR = 0.77, 95% CI 0.60-1.00, p value for interaction = 0.259), and 0.70 (95% CI 0.51-0.96) for metformin (compared to use of non-metformin antidiabetics) (ER+: HR = 0.67, 95% CI 0.45-1.01; ER-: HR = 1.62, 95% CI 0.72-3.62, p value for interaction = 0.077). CONCLUSION: We found evidence supporting an association between post-diagnostic use of statins and metformin and survival, in patients with BC. Our findings indicate potential differences according to ER status.

A population-based cohort study on changes in breast, lung and colorectal cancer incidence and mortality among non-Western immigrant women.

BACKGROUND: Cancer risk varies geographically, and migrants are influenced by different risk factors before, during and after migration. Increased migration from non-Western countries to the Nordic countries calls for a better understanding of the migrants' cancer risk and the change in risk patterns over time. The aim of this study was to compare the incidence and mortality of breast, colorectal and lung cancer between non-Western immigrant and the native female population in Denmark, Finland, Iceland, and Norway. MATERIAL AND METHODS: Data from national registries were processed and pre-analysed in each country. Multivariate Poisson regression models were used to model the relative differences in incidence and mortality as rate ratios (RR). The country-specific estimates and summary statistics were pooled together using a random effects model. RESULTS: Non-Western immigrant women had significantly lower breast (RR 0.71, 0.65-0.78), colorectal (RR 0.72, 0.57-0.92) and lung (RR 0.55, 0.42-0.72) cancer incidence rates than native women, and the risk of these cancers among immigrant women increased with duration of residence. Differences were parallel in breast, colorectal and lung cancer mortality (RR 0.64, 0.55-0.74; RR 0.66, 0.48-0.92; RR 0.51, 0.34-0.79). Among immigrant women, higher education increased the risk for breast cancer and decreased it for lung cancer. CONCLUSION: The results significantly complement and add to the previous findings of cancer burden and cancer burden transition among migrants and provide evidence of a prolonged cancer risk advantage among non-Western immigrant women. However, the findings show an increasing risk of lifestyle-related cancers with increasing duration of residence in the host country. Further studies are needed to discover underlying reasons for this phenomenon.

Coping After Breast Cancer: Protocol for a Randomized Controlled Trial of Stress Management eHealth Interventions.

BACKGROUND: One-third or more of breast cancer survivors report stress and other psychological and physical complaints that can negatively impact their quality of life. Psychosocial stress management interventions, shown to mitigate the negative impact of these complaints, can now be delivered as accessible and convenient (for the patient and provider) eHealth interventions. In this randomized controlled trial (RCT), Coping After Breast Cancer (CABC), 2 modified versions of the stress management eHealth intervention program StressProffen were created: one with predominantly cognitive behavioral stress management content (StressProffen-cognitive behavioral therapy intervention [StressProffen-CBI]) and another with predominantly mindfulness-based stress management content (StressProffen-mindfulness-based intervention [StressProffen-MBI]). OBJECTIVE: This study aims to investigate the effects in breast cancer survivors of using StressProffen-CBI and StressProffen-MBI compared with a control group (treatment as usual). METHODS: Women diagnosed with breast cancer (stage I-III, unequivocally human epidermal growth factor receptor 2-positive or estrogen receptor-negative tumors) or ductal carcinoma in situ (DCIS) aged 21-69 years who completed the Cancer Registry of Norway-initiated health survey on quality of life are invited to the CABC trial about 7 months after diagnosis. Women who give consent to participate are randomized (1:1:1) to either the StressProffen-CBI, StressProffen-MBI, or control group. Both StressProffen interventions consist of 10 modules of stress management content delivered through text, sound, video, and images. The primary outcome is between-group changes in perceived stress at 6 months, assessed with Cohen 10-item Perceived Stress Scale. The secondary outcomes comprise changes in quality of life, anxiety, depression, fatigue, sleep, neuropathy, coping, mindfulness, and work-related outcomes approximately 1, 2, and 3 years after diagnosis. Long-term effects of the interventions on work participation, comorbidities, relapse or new cancers, and mortality will be assessed using data from national health registries. RESULTS: Recruitment is scheduled from January 2021 to May 2023. The goal is to recruit 430 participants (100 in each group). As of April 14 2023, 428 participants have been enrolled. CONCLUSIONS: The CABC trial is possibly the largest ongoing psychosocial eHealth RCT in patients with breast cancer. If 1 or both interventions prove to be effective in reducing stress and improving psychosocial and physical complains, the StressProffen eHealth interventions could be beneficial, inexpensive, and easily implementable tools for breast cancer survivors when coping with late effects after cancer and cancer treatments. TRIAL REGISTRATION: Clinicaltrials.gov NCT04480203; https://clinicaltrials.gov/ct2/show/NCT04480203. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47195.

Low-dose aspirin and risk of breast cancer: a Norwegian population-based cohort study of one million women.

Several studies evaluated the association between aspirin use and risk of breast cancer (BC), with inconsistent results. We identified women aged ≥ 50 years residing in Norway between 2004 and 2018, and linked data from nationwide registries; including the Cancer Registry of Norway, the Norwegian Prescription Database, and national health surveys. We used Cox regression models to estimate the association between low-dose aspirin use and BC risk, overall and by BC characteristics, women's age and body mass index (BMI), adjusting for sociodemographic factors and use of other medications. We included 1,083,629 women. During a median follow-up of 11.6 years, 257,442 (24%) women used aspirin, and 29,533 (3%) BCs occurred. For current use of aspirin, compared to never use, we found an indication of a reduced risk of oestrogen receptor-positive (ER +) BC (hazard ratio [HR] = 0.96, 95% confidence interval [CI]: 0.92-1.00), but not ER-negative BC (HR = 1.01, 95%CI: 0.90-1.13). The association with ER + BC was only found in women aged ≥ 65 years (HR = 0.95, 95%CI: 0.90-0.99), and became stronger as the duration of use increased (use of ≥ 4 years HR = 0.91, 95%CI: 0.85-0.98). BMI was available for 450,080 (42%) women. Current use of aspirin was associated with a reduced risk of ER + BC in women with BMI ≥ 25 (HR = 0.91, 95%CI: 0.83-0.99; HR = 0.86, 95%CI: 0.75-0.97 for use of ≥ 4 years), but not in women with BMI < 25.Use of low-dose aspirin was associated with reduced risk of ER + BC, in particular in women aged ≥ 65 years and overweight women.

Circulating vitamin D and breast cancer risk: an international pooling project of 17 cohorts.

Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42-68) years at blood collection and 63 (49-75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, calibrated to this assay to permit using a common metric. Study-specific relative risks (RRs) for season-standardized 25(OH)D concentrations were estimated by conditional logistic regression and combined by random-effects models. Circulating 25(OH)D increased from a median of 22.6 nmol/L in consortium-wide decile 1 to 93.2 nmol/L in decile 10. Breast cancer risk in each decile was not statistically significantly different from risk in decile 5 in models adjusted for breast cancer risk factors, and no trend was apparent (P-trend = 0.64). Compared to women with sufficient 25(OH)D based on Institute of Medicine guidelines (50- < 62.5 nmol/L), RRs were not statistically significantly different at either low concentrations (< 20 nmol/L, 3% of controls) or high concentrations (100- < 125 nmol/L, 3% of controls; ≥ 125 nmol/L, 0.7% of controls). RR per 25 nmol/L increase in 25(OH)D was 0.99 [95% confidence intervaI (CI) 0.95-1.03]. Associations remained null across subgroups, including those defined by body mass index, physical activity, latitude, and season of blood collection. Although none of the associations by tumor characteristics reached statistical significance, suggestive inverse associations were seen for distant and triple negative tumors. Circulating 25(OH)D, comparably measured in 17 international cohorts and season-standardized, was not related to subsequent incidence of invasive breast cancer over a broad range in vitamin D status.

Survival trends for patients with primary metastatic prostate cancer before and after the introduction of new antitumor drugs.

BACKGROUND: During the past two decades, new antitumor drugs (Abiraterone, Enzalutamide, Radium-223, Cabazitaxel, and Docetaxel) have been introduced for treatment of prostate cancer with distant metastases (mPCa). Each drug have demonstrated a survival gain in studies, but little is known about the impact in a general population of mPCa patients. In this study we assessed survival before and after introduction of the new drugs for Norwegian mPCa patients. METHODS: Survival was assessed in 5542 patients with primary mPCa. The patients were diagnosed between 2004 and 2018, identified in the Norwegian Cancer Registry. We also analyzed a subgroup of 2738 patients possibly eligible for treatment with new drugs (age <80 years, WHO performance status ≤2 and not dead within 3 months from diagnosis). We estimated overall (OS) and cause-specific survival (CSS) across three diagnostic time periods reflecting to the drugs' introduction in Norway: Before (2004-2009), "in between" (2010-2014) and after the introduction (2015-2018). We used Kaplan-Meier survival analysis and multivariable Cox regression. RESULTS: Median OS increased from 2.3 years in 2004-2009 to 3.3 years in 2015-2018. 3-year OS improved from 41% in 2004-2009 to 51% in 2015-2018. An earlier diagnostic period, a more advanced T stage, higher ISUP grade group, lower WHO status and higher PSA levels were associated with a lower CSS. Similar results was found for the subgroup. CONCLUSIONS: Median OS of mPCa has increased by one year since 2004 for mPCa patients in Norway. Survival improvement persisted after adjustment for recognized prognostic factors and may be related to the introduction of new drugs in Norway.

The association of age at menarche and adult height with mammographic density in the International Consortium of Mammographic Density.

BACKGROUND: Early age at menarche and tall stature are associated with increased breast cancer risk. We examined whether these associations were also positively associated with mammographic density, a strong marker of breast cancer risk. METHODS: Participants were 10,681 breast-cancer-free women from 22 countries in the International Consortium of Mammographic Density, each with centrally assessed mammographic density and a common set of epidemiologic data. Study periods for the 27 studies ranged from 1987 to 2014. Multi-level linear regression models estimated changes in square-root per cent density (√PD) and dense area (√DA) associated with age at menarche and adult height in pooled analyses and population-specific meta-analyses. Models were adjusted for age at mammogram, body mass index, menopausal status, hormone therapy use, mammography view and type, mammographic density assessor, parity and height/age at menarche. RESULTS: In pooled analyses, later age at menarche was associated with higher per cent density (ß√PD = 0.023 SE = 0.008, P = 0.003) and larger dense area (ß√DA = 0.032 SE = 0.010, P = 0.002). Taller women had larger dense area (ß√DA = 0.069 SE = 0.028, P = 0.012) and higher per cent density (ß√PD = 0.044, SE = 0.023, P = 0.054), although the observed effect on per cent density depended upon the adjustment used for body size. Similar overall effect estimates were observed in meta-analyses across population groups. CONCLUSIONS: In one of the largest international studies to date, later age at menarche was positively associated with mammographic density. This is in contrast to its association with breast cancer risk, providing little evidence of mediation. Increased height was also positively associated with mammographic density, particularly dense area. These results suggest a complex relationship between growth and development, mammographic density and breast cancer risk. Future studies should evaluate the potential mediation of the breast cancer effects of taller stature through absolute breast density.

ß-blockers and breast cancer survival by molecular subtypes: a population-based cohort study and meta-analysis.

BACKGROUND: The association between use of ß-blockers and breast cancer (BC) prognosis has been investigated in several observational studies, with conflicting results. We performed a nationwide cohort study and a meta-analysis to investigate the association, and assess if it varied between molecular subtypes of BC. METHODS: We identified women aged ≥50 years with BC diagnosed between 2004 and 2018 in Norway. We used Cox regression models to estimate the association between ß-blocker use at diagnosis and BC-specific survival, overall and by molecular subtype. We performed a meta-analysis of observational studies that reported molecular subtype-specific estimates of this association. RESULTS: We included 30,060 women, of which 4461 (15%) used ß-blockers. After a median follow-up of 5.1 years, 2826 (9%) died of BC. Overall, ß-blocker use was not associated with BC-specific survival (hazard ratio [HR] = 1.07; 95% confidence interval [CI]: 0.97-1.19). We found an association only in triple-negative BC (TNBC) patients (HR = 0.66; 95% CI: 0.47-0.91). This was confirmed in the meta-analysis: ß-blocker use was associated with progression/recurrence-free (HR = 0.58; 95% CI: 0.38-0.89) and BC-specific survival (HR = 0.74; 95% CI: 0.55-1.00) in TNBC patients only. CONCLUSION: In our cohort of BC patients and in the meta-analysis, ß-blocker use was associated with prolonged BC-specific survival only in TNBC patients.

The impact of the COVID-19 pandemic on cancer diagnosis based on pathology notifications: A comparison across the Nordic countries during 2020.

The severity of the COVID-19 pandemic and subsequent mitigation strategies have varied across the Nordic countries. In a joint Nordic population-based effort, we compared patterns of new cancer cases and notifications between the Nordic countries during 2020. We used pathology notifications to cancer registries in Denmark, the Faroe Islands, Finland, Iceland, Norway and Sweden to determine monthly numbers of pathology notifications of malignant and in situ tumours from January to December 2020 compared to 2019 (2017-2019 for Iceland and the Faroe Islands). We compared new cancer cases per month based on unique individuals with pathology notifications. In April and May 2020, the numbers of new malignant cases declined in all Nordic countries, except the Faroe Islands, compared to previous year(s). The largest reduction was observed in Sweden (May: -31.2%, 95% CI -33.9, -28.3), followed by significant declines in Finland, Denmark and Norway, and a nonsignificant decline in Iceland. In Denmark, Norway, Sweden and Finland the reporting rates during the second half of 2020 rose to almost the same level as in 2019. However, in Sweden and Finland, the increase did not compensate for the spring decline (annual reduction -6.2% and -3.6%, respectively). Overall, similar patterns were observed for in situ tumours. The COVID-19 pandemic led to a decline in rates of new cancer cases in Sweden, Finland, Denmark and Norway, with the most pronounced reduction in Sweden. Possible explanations include the severity of the pandemic, temporary halting of screening activities and changes in healthcare seeking behaviour.