BRCA2 mutation carriers, reproductive factors and breast cancer risk

BACKGROUND: Germline mutations in the BRCA genes dramatically increase the risk of breast cancer. In the general population, breast cancer risk is affected by age at menarche, by age at first birth, by the number of births and by the duration of breast feeding. Whether this is true for mutation carriers is not clear. METHODS: In a case–control study, nested in a population-based cohort of the Icelandic Cancer Detection Clinic, two groups of cases were defined, matched on year of birth, on age at diagnosis and on age when giving information on reproductive factors: 100 carriers of the Icelandic founder BRCA2 mutation 999del5, and 361 BRCA2-negative cases. The mean age at diagnosis was 48 years. There were 1000 women in a matched group of unaffected controls. Conditional logistic regression was used for the analysis. RESULTS: An increased number of births was associated with a decreased risk of breast cancer in BRCA2-negative cases but not in BRCA2-positive cases. A negative association between risk and duration of breast feeding was observed only in the mutation carriers. These associations were not statistically significant, but the effects of the two variables differed significantly according to mutation status (P = 0.007 and P = 0.045 for interaction with number of births and with duration of breast feeding, respectively). This was maintained when limiting the analysis to women diagnosed older than the age of 40 years. CONCLUSION: The association between breast cancer and the number of pregnancies and between breast cancer and the duration of breast feeding was not the same for carriers and noncarriers of a detrimental BRCA2 mutation. In the context of other epidemiological and laboratory studies, this may indicate that the product of the BRCA2 gene has a function relating to the differentiation of epithelial tissue in the breast

Survival trends in patients diagnosed with colon and rectal cancer in the nordic countries 1990-2016 : The NORDCAN survival studies

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.Peer reviewe

Trends in cancer survival in the Nordic countries 1990-2016 : the NORDCAN survival studies

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.Peer reviewe

Age-specific survival trends and life-years lost in women with breast cancer 1990-2016 : the NORDCAN survival studies

BackgroundA recent overview of cancer survival trends 1990-2016 in the Nordic countries reported continued improvements in age-standardized breast cancer survival among women. The aim was to estimate age-specific survival trends over calendar time, including life-years lost, to evaluate if improvements have benefited patients across all ages in the Nordic countries.MethodsData on breast cancers diagnosed 1990-2016 in Denmark, Finland, Iceland, Norway, and Sweden were obtained from the NORDCAN database. Age-standardized and age-specific relative survival (RS) was estimated using flexible parametric models, as was reference-adjusted crude probabilities of death and life-years lost.ResultsAge-standardized period estimates of 5-year RS in women diagnosed with breast cancer ranged from 87% to 90% and 10-year RS from 74% to 85%. Ten-year RS increased with 15-18 percentage points from 1990 to 2016, except in Sweden (+9 percentage points) which had the highest survival in 1990. The largest improvements were observed in Denmark, where a previous survival disadvantage diminished. Most recent 5-year crude probabilities of cancer death ranged from 9% (Finland, Sweden) to 12% (Denmark, Iceland), and life-years lost from 3.3 years (Finland) to 4.6 years (Denmark). Although survival improvements were consistent across different ages, women aged >= 70 years had the lowest RS in all countries. Period estimates of 5-year RS were 94-95% in age 55 years and 84-89% in age 75 years, while 10-year RS were 88-91% in age 55 years and 69-84% in age 75 years. Women aged 40 years lost on average 11.0-13.8 years, while women lost 3.8-6.0 years if aged 55 and 1.9-3.5 years if aged 75 years.ConclusionsSurvival for Nordic women with breast cancer improved from 1990 to 2016 in all age groups, albeit with larger country variation among older women where survival was also lower. Women over 70 years of age have not had the same survival improvement as women of younger age.Peer reviewe

Tall cell variant of papillary thyroid carcinoma: a population-based study in Iceland.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageThe tall cell variant (TCV) of papillary thyroid carcinoma (PTC) is an aggressive variant of PTC that is believed to have worse outcomes than classical PTC. The objective of this study was to investigate the incidence, survival, and disease recurrence of patients with TCV and compare them with other PTC in a whole population.Information on all thyroid carcinomas diagnosed in Iceland from 1990 to 2009 was obtained from the Icelandic Cancer Registry. PTC diagnosed postmortem was excluded. The date of diagnosis, sex, and age at diagnosis were registered. All histopathology material was re-evaluated, and papillary thyroid tumors classified as either TCV or other types of PTC. Tumors were classified as TCV if >50% of cells were tall (height > twice the width). TNM stage was determined for all the cases. Endpoints were thyroid cancer-specific death and thyroid cancer recurrence.Out of 376 patients diagnosed with PTC in the study period, 49 (13%) were classified as TCV. Patients with TCV were older (66 years vs. 49 years, p<0.001), more often had pT4 tumors (71% vs. 15%, p<0.001), had higher rates of nodal metastasis (51% vs. 22%, p<0.001), and more often distant metastasis (14% vs. 2%, p<0.001). The age-adjusted incidence of TCV for men was 0.5/100,000 [confidence interval (CI) 0.3-0.7] and for women 0.7/100,000 [CI 0.4-1.0] between 1990 and 2009. The five-year disease-specific survival for TCV was 83% [CI 68-91] compared to 98% [CI 96-99] for other PTC respectively (p<0.001). In multivariate analysis, TCV histology was an independent risk factor for recurrence (hazard ratio (HR) 3.18 [CI 1.48-6.84]) but not for disease specific survival (HR 1.86 [CI 0.77-4.73]).TCV comprises 13% of all diagnosed PTC in Iceland with an incidence of 0.5/100,000 for men and 0.7/100,000 for women. Patients diagnosed with TCV have worse five-year disease-specific survival than patients with other PTC. TCV histology is an independent risk factor for disease recurrence but not for disease-specific survival

Skimun fyrir krabbameinum í ristli og endaþarmi : Yfirlitsgrein um nýgengi, dánartíðni, kostnað og árangur

In this article the incidence and mortality for cancer of the colon and rectum in Iceland is discussed. The two most common screening methods, faecal immunochemical test (FIT) and colonoscopy are compared and an estimate of cost and benefits for the Icelandic society will be made. The incidence of cancer of the colon and rectum has been increasing in Iceland in last decades but mortality has decreased and survival improved. However, more individuals die from cancer of the colon and rectum than from both breast-and cervical cancer added together. It is likely that screening for cancer of the colon and rectum, could prevent at least 6 of the 28 deaths related to those cancers, occurring yearly in Iceland in screening age, given a screening ages of 50-74 years. The extra cost for the Icelandic community due to the implementation of screening for cancer of the colon and rectum will be acceptable due to the lower cost of simpler treatments, lower cancer incidence and reduced mortality.Nýgengi krabbameina í ristli og endaþarmi hefur aukist hjá bæði konum og körlum síðustu áratugina en dánartíðni hefur heldur lækkað frá sjötta áratugnum og lifun batnað vegna betri greiningar og meðferðar. Fjöldi þeirra sem látast úr ristil- og endaþarmskrabbameini er þó meiri en úr brjósta- og leghálskrabbameinum samanlagt. Viðfangsefni greinarinnar eru nýgengi og dánartíðni krabbameina í ristli og endaþarmi hérlendis. Fjallað er um tvær algengustu skimunaraðferðirnar, leit að blóði í hægðum og ristilspeglun. Þá er lagt mat á ætlaðan kostnað og ávinninning íslensks samfélags af því að skima fyrir krabbameinum í ristli og endaþarmi. Líklegt er að á Íslandi geti skipulögð lýðgrunduð skimun fyrir krabbameinum í ristli og endaþarmi komið í veg fyrir að minnsta kosti 6 dauðsföll af þeim 28 á ári sem verða úr sjúkdómnum meðal fólks á skimunaraldri, ef skimunaraldur verður 50-74 ára. Umframkostnaður fyrir samfélagið vegna skimunar fyrir krabbameinum í ristli og endaþarmi er talinn mjög ásættanlegur í ljósi þess að sparnaður verður vegna einfaldari meðferðar, lækkunar nýgengis og fækkunar dauðsfalla.English title in Web of Science: Screening for cancer of the colon and rectum A review on incidence, mortality, cost and benefit.</p

Estrogen-progestin use and breast cancer characteristics in lean and overweight postmenopausal women.

To access publisher's full text version of this article click on the hyperlink belowBreast cancer associated with estrogen-progestin (EP) therapy may have more favorable characteristics than cancer in never users, but results are conflicting. It is not well known either whether Body Mass Index (BMI) modifies this association. We investigated breast cancer characteristics in EP users for lean (BMI < 25 kg/m(2)) and overweight women (BMI ≥ 25 kg/m(2)).The Icelandic Cancer Detection Clinic cohort, with information on breast cancer risk factors for 90% of Icelandic women, was linked with the population-based Icelandic Cancer Registry. A total of 781 women with invasive breast cancer diagnosed 51 years or older were matched with 7761 controls from the cohort. Conditional logistic regression was used for estimating adjusted odds ratios (OR) and 95% confidence intervals (CI) according to tumor characteristics, stratified by BMI. Polytomous logistic regression was applied in a case-only analysis for testing whether the risk associated with EP use differed according to tumor characteristics.Ever EP users had a twofold higher risk of breast cancer compared with never users (OR 2.05, 95% CI 1.71-2.45). In lean women, EP use was significantly less likely to be associated with grade 2 or 3 tumors than grade 1 tumors, contrary to overweight women for whom risk was increased irrespective of grade. EP use in overweight women was associated with a higher risk of lobular than ductal cancer (OR 2.75, 95% CI 1.29-5.87).Among lean EP users, tumor characteristics were more favorable than among never users. This effect was not observed for overweight women.Icelandic Cancer Societ