Non-progressive breast carcinomas detected at mammography screening: a population study.

BACKGROUND: Some breast carcinomas detected at screening, especially ductal carcinoma in situ, may have limited potential for progression to symptomatic disease. To determine non-progression is a challenge, but if all screening-detected breast tumors eventually reach a clinical stage, the cumulative incidence at a reasonably high age would be similar for women with or without screening, conditional on the women being alive. METHODS: Using high-quality population data with 24 years of follow-up from the gradually introduced BreastScreen Norway program, we studied whether all breast carcinomas detected at mammography screening 50-69 years of age would progress to clinical symptoms within 85 years of age. First, we estimated the incidence rates of breast carcinomas by age in scenarios with or without screening, based on an extended age-period-cohort incidence model. Next, we estimated the frequency of non-progressive tumors among screening-detected cases, by calculating the difference in the cumulative rate of breast carcinomas between the screening and non-screening scenarios at 85 years of age. RESULTS: Among women who attended BreastScreen Norway from the age of 50 to 69 years, we estimated that 1.1% of the participants were diagnosed with a breast carcinoma without the potential to progress to symptomatic disease by 85 years of age. This proportion of potentially non-progressive tumors corresponded to 15.7% [95% CI 3.3, 27.1] of breast carcinomas detected at screening. CONCLUSIONS: Our findings suggest that nearly one in six breast carcinomas detected at screening may be non-progressive.

Pregnancy complications in last pregnancy and mothers' long-term cardiovascular mortality: does the relation differ from that of complications in first pregnancy? A population-based study.

BACKGROUND: Women who experience complications in first pregnancy are at increased risk of cardiovascular disease (CVD) later in life. Little corresponding knowledge is available for complications in later pregnancies. Therefore, we assessed complications (preeclampsia, preterm birth, and offspring small for gestational age) in first and last pregnancies and the risk of long-term maternal CVD death, taking women´s complete reproduction into account. DATA AND METHODS: We linked data from the Medical Birth Registry of Norway to the national Cause of Death Registry. We followed women whose first birth took place during 1967-2013, from the date of their last birth until death, or December 31st 2020, whichever occurred first. We analysed risk of CVD death until 69 years of age according to any complications in last pregnancy. Using Cox regression analysis, we adjusted for maternal age at first birth and level of education. RESULTS: Women with any complications in their last or first pregnancy were at higher risk of CVD death than mothers with two-lifetime births and no pregnancy complications (reference). For example, the adjusted hazard ratio (aHR) for women with four births and any complications only in the last pregnancy was 2.85 (95% CI, 1.93-4.20). If a complication occurred in the first pregnancy only, the aHR was 1.74 (1.24-2.45). Corresponding hazard ratios for women with two births were 1.82 (CI, 1.59-2.08) and 1.41 (1.26-1.58), respectively. CONCLUSIONS: The risk for CVD death was higher among mothers with complications only in their last pregnancy compared to women with no complications, and also higher compared to mothers with a complication only in their first pregnancy.

FGD5 amplification in breast cancer patients is associated with tumour proliferation and a poorer prognosis.

PURPOSE: Proliferation is a hallmark of cancer. Using a combined genomic approach, FGD5 amplification has been identified as a driver of proliferation in Luminal breast cancer. We aimed to describe FGD5 copy number change in breast cancer, and to assess a possible association with tumour proliferation and prognosis. METHODS: We used fluorescence in situ hybridization targeting FGD5 and chromosome 3 centromere (CEP3) on formalin-fixed, paraffin-embedded tissue from 430 primary breast cancers and 108 lymph node metastases, from a cohort of Norwegian breast cancer patients. We tested the association between FGD5 copy number status and proliferation (assessed by Ki67 levels and mitotic count) using Pearson's Chi square test, and assessed the prognostic impact of FGD5 copy number change by estimating cumulative risks of death and hazard ratios. RESULTS: We identified FGD5 amplification (defined as FGD5/CEP3 ratio ≥2 or mean FGD5/tumour cell ≥4) in 9.5% of tumours. Mitotic count and Ki67 levels were higher in tumours with FGD5 copy number increase, compared to tumours with no copy number change. After 10 years of follow-up, cumulative risk of death from breast cancer was higher among cases with FGD5 amplification [48.1% (95% CI 33.8-64.7)], compared to non-amplified cases [27.7% (95% CI 23.4-32.6)]. CONCLUSIONS: FGD5 is a new prognostic marker in breast cancer, and increased copy number is associated with higher tumour proliferation and poorer long-term prognosis.

Insomnia and the Risk of Breast Cancer: The HUNT Study.

OBJECTIVE: The association of insomnia with subsequent breast cancer risk is largely unknown. Therefore, we assessed whether different symptoms of insomnia and their combination are associated with incident breast cancer in a large population-based study. METHODS: In a prospective cohort study, 33,332 women were followed to monitor the occurrence of their first invasive breast cancer identified by the Cancer Registry of Norway. Insomnia symptoms including () nonrestorative sleep and () difficulty initiating and () maintaining sleep were self-reported using a study specific measure reflecting the current Diagnostic and Statistical Manual of Mental Disorders criteria. Hazard ratios and 95% confidence intervals were calculated using multiadjusted Cox proportional hazards models. RESULTS: A total of 862 incident breast cancer cases occurred during a mean follow-up of 14.7 years. No consistent association was observed between the individual insomnia symptoms and breast cancer risk. However, compared to women reporting no insomnia complaints, those who reported having all three aspects of insomnia simultaneously were at increased risk (hazard ratio, 2.38; 95% confidence interval = 1.11-5.09). CONCLUSION: Our results suggest that having only some aspects of insomnia may not predispose someone to breast cancer. In contrast, experiencing all insomnia symptoms simultaneously might confer considerable excess risk.

Size at birth and risk of breast cancer: update from a prospective population-based study.

Birth size variables (birth weight, birth length and head circumference) have been reported to be positively associated with adult breast cancer risk, whereas a possible association of placental weight has not been adequately studied. It has also been suggested that maternal height may modify the association of birth size with adult breast cancer risk, but this has not been studied in detail. We updated a long-term follow-up of 22,931 Norwegian women (average of 51 years of follow up during which 870 women were diagnosed with breast cancer) and assessed placental weight in relation to breast cancer risk, in addition to providing updated analyses on breast cancer risk in relation to birth weight, birth length and head circumference. Placental weight was not associated with risk for breast cancer in adulthood, but there was a positive association of breast cancer risk with birth length (HR 1.13, 95% CI 1.05-1.21, per 2 cm increment), though not with birth weight (HR 1.02, 95% CI 0.95-1.10 per 0.5 kg increment). For birth length, the graded increase in risk was particularly strong among women whose mothers were relatively tall (p for trend, 0.001), compared to the trend among women whose mothers were relatively short (p for trend, 0.221). The results showed a robust and positive association of birth length with breast cancer risk, and may be especially strong in women whose mothers were relatively tall. We found no association of placental weight with risk for breast cancer.

Physical activity and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis.

We investigated the association between specific types of physical activity and the risk of type 2 diabetes in a systematic review and meta-analysis of published studies. PubMed, Embase and Ovid databases were searched for prospective studies and randomized trials up to 2nd of March 2015. Summary relative risks (RRs) were calculated using a random effects model. Eighty-one studies were included. The summary RRs for high versus low activity were 0.65 (95 % CI 0.59-0.71, I(2) = 18 %, n = 14) for total physical activity, 0.74 (95 % CI 0.70-0.79, I(2) = 84 %, n = 55) for leisure-time activity, 0.61 (95 % CI 0.51-0.74, I(2) = 73 %, n = 8) for vigorous activity, 0.68 (95 % CI 0.52-0.90, I(2) = 93 %, n = 5) for moderate activity, 0.66 (95 % CI 0.47-0.94, I(2) = 47 %, n = 4) for low intensity activity, and 0.85 (95 % CI 0.79-0.91, I(2) = 0 %, n = 7) for walking. Inverse associations were also observed for increasing activity over time, resistance exercise, occupational activity and for cardiorespiratory fitness. Nonlinear relations were observed for leisure-time activity, vigorous activity, walking and resistance exercise (p nonlinearity < 0.0001 for all), with steeper reductions in type 2 diabetes risk at low activity levels than high activity levels. This meta-analysis provides strong evidence for an inverse association between physical activity and risk of type 2 diabetes, which may partly be mediated by reduced adiposity. All subtypes of physical activity appear to be beneficial. Reductions in risk are observed up to 5-7 h of leisure-time, vigorous or low intensity physical activity per week, but further reductions cannot be excluded beyond this range.

Do parental heights influence pregnancy length?: A population-based prospective study, HUNT 2.

BACKGROUND: The objective of this study was to examine the association of maternal and paternal height with pregnancy length, and with the risk of pre- and post-term birth. In addition we aimed to study whether cardiovascular risk factors could explain possible associations. METHODS: Parents who participated in the Nord-Trøndelag Health Study (HUNT 2; 1995-1997) were linked to offspring data from the Medical Birth Registry of Norway (1997-2005). The main analyses included 3497 women who had delivered 5010 children, and 2005 men who had fathered 2798 pregnancies. All births took place after parental participation in HUNT 2. Linear regression was used to estimate crude and adjusted differences in pregnancy length according to parental heights. Logistic regression was used to estimate crude and adjusted associations of parental heights with the risk of pre- and post-term births. RESULTS: We found a gradual increase in pregnancy length by increasing maternal height, and the association was essentially unchanged after adjustment for maternal cardiovascular risk factors, parental age, offspring sex, parity, and socioeconomic measures. When estimated date of delivery was based on ultrasound, the difference between mothers in the lower height quintile (<163 cm cm) and mothers in the upper height quintile (≥ 173 cm) was 4.3 days, and when estimated date of delivery was based on last menstrual period (LMP), the difference was 2.8 days. Shorter women (< 163 cm) had lower risk of post-term births, and when estimated date of delivery was based on ultrasound they also had higher risk of pre-term births. Paternal height was not associated with pregnancy length, or with the risks of pre- and post-term births. CONCLUSIONS: Women with shorter stature had shorter pregnancy length and lower risk of post-term births than taller women, and when EDD was based on ultrasound, they also had higher risk of preterm births. The effect of maternal height was generally stronger when pregnancy length was based on second trimester ultrasound compared to last menstrual period. The association of maternal height with pregnancy length could not be explained by cardiovascular risk factors. Paternal height was neither associated with pregnancy length nor with the risk of pre- and post-term birth.

Offspring birth weight and cardiovascular risk in parents: a population-based HUNT 2 study.

Low birth weight is associated with increased risk of cardiovascular disease and type 2 diabetes in later life. The fetal insulin hypothesis suggests that shared genetic factors partly explain this association. If fetal genes predispose to both low birth weight and cardiovascular disease in adulthood, fathers of offspring with low birth weight should display an unfavorable profile of cardiovascular risk factors. To study this, the authors linked data on more than 14,000 parents, collected from the second Health Study of Nord Trøndelag County, Norway (HUNT 2, 1995-1997), to offspring data from the Norwegian Medical Birth Registry (1967-2005). Linear regression was used to study associations of offspring birth weight for gestational age with the parents' body mass index, waist circumference, blood pressure, glucose, and serum lipids. All analyses were adjusted for shared environment by means of the socioeconomic measures, lifestyle, and cardiovascular risk factors of the partner. The authors found that low offspring birth weight for gestational age was associated with increased paternal blood pressure, body mass index, waist circumference, and unfavorable levels of glucose and lipids. For mothers, associations similar to those for fathers were found for blood pressure, whereas associations in the opposite direction were found for glucose, lipids, and body mass index. The paternal findings strengthen the genetic hypothesis.

Insomnia and high-sensitivity C-reactive protein: the HUNT study, Norway.

OBJECTIVE: To explore the hypothesis that insomnia may increase the risk of coronary heart disease through inflammatory mechanisms. METHODS: The association of high-sensitivity C-reactive protein (hsCRP) with self-reported symptoms of insomnia was examined. Participants were 8547 men and nonpregnant women who answered one or more insomnia-related questions and who had available hsCRP measurements in the Nord-Trøndelag Health Study. In multivariable linear regression analyses of the logarithm of hsCRP, we adjusted for established cardiovascular risk factors, psychosocial distress, chronic pain, and chronic somatic disorders. RESULTS: Among men, difficulties initiating sleep and nonrestorative sleep were associated with increasing hsCRP levels after adjusting for age (B = 0.07, 95% confidence interval [CI] = 0.01-0.14, p for trend = .02 and B = 0.09, 95% CI = 0.02-0.15, p for trend = .006), but after multivariable adjustment, the associations were attenuated (B = 0.03, 95% CI = -0.03 to 0.09, p for trend = .30 and B = 0.06, 95% CI = -0.00 to 0.12, p for trend = .05). HsCRP was not associated with other insomnia-related symptoms. In women, there was no evidence for any association of symptoms of insomnia with hsCRP levels. Results indicated sex differences in the association between sleep characteristics and CRP (difficulties maintaining sleep, p interaction = .018; cumulative number of symptoms of insomnia, p interaction = .014; and symptoms of insomnia influencing work performance, p interaction = .039). CONCLUSIONS: There were no consistent associations between symptoms of insomnia and hsCRP levels. Our results do not support the hypothesis that inflammation, as reflected by elevated levels of hsCRP, is an important factor linking insomnia to coronary heart disease.

Interpreting Breast Cancer Mortality Trends Related to Introduction of Mammography Screening: A Simulation Study.

Background. Several studies have evaluated the effect of mammography screening on breast cancer mortality based on overall breast cancer mortality trends, with varied conclusions. The statistical power of such trend analyses is, however, not carefully studied. Methods. We estimated how the effect of screening on overall breast cancer mortality is likely to unfold. Because a screening effect is based on earlier treatment, screening can affect only new incident cases after screening introduction. To evaluate the likelihood of detecting screening effects on overall breast cancer mortality time trends, we calculated the statistical power of joinpoint regression analysis on breast cancer mortality trends around screening introduction using simulations. Results. We found that a very gradual increase in population-level screening effect is expected due to prescreening incident cases. Assuming 25% effectiveness of a biennial screening program in reducing breast cancer mortality among women 50 to 69 y of age, the expected reduction in overall breast cancer mortality was 3% after 2 y and reached a long-term effect of 18% after 20 y. In common settings, the statistical power to detect any screening effects using joinpoint regression analysis is very low (<50%), even in an artificial setting of constant risk of baseline breast cancer mortality over time. Conclusions. Population effects of screening on breast cancer mortality emerge very gradually and are expected to be considerably lower than the effects reported in trials excluding women diagnosed before screening. Studies of overall breast cancer mortality time trends have too low statistical power to reliably detect screening effects in most populations. Implications. Researchers and policy makers evaluating mammography screening should avoid using breast cancer mortality trend analysis that does not separate pre- and postscreening incident cases. Highlights: Population-level mammography screening effects on breast cancer mortality emerge gradually following screening introduction, resulting in very low statistical power of trend analysis.Researchers and policy makers evaluating mammography screening should avoid relying on population-wide breast cancer mortality trends.Expected mammography screening effects at population level are lower than those from screening trials, as many cases of breast cancer fall outside the screening age range.

How do busy hospital circumstances affect mortality and readmission within 60 days: A cohort study of 680 000 acute admissions in Norway.

OBJECTIVE: To study mortality and readmissions for older patients admitted during more and less busy hospital circumstances. DESIGN: Cohort study where we identified patients that were admitted to the same hospital, during the same month and day of the week. We estimated effects of inflow of acute patients and the number of concurrent acute inpatients. Mortality and readmissions were analysed using stratified Cox-regression. SETTING: All people 80 years and older acutely admitted to Norwegian hospitals between 2008 and 2016. MAIN OUTCOME MEASURES: Mortality and readmissions within 60 days from admission. RESULTS: Among 294 653 patients with 685 197 admissions, mean age was 86 years (standard deviation 5). Overall, 13% died within 60 days. An interquartile range difference in inflow of acute patients was associated with a hazard ratio (HR) of 0.99, 95% confidence interval (95% CI) 0.98 to 1.00). There was little evidence of differences in readmissions, but a 7% higher risk (HR 1.07, 95% CI 1.06 to 1.09) of being discharged outside ordinary daytime working hours. CONCLUSIONS: Older patients admitted during busier circumstances had similar mortality and readmissions to those admitted during less busy periods. Yet, they showed a higher risk of discharge outside daytime working hours. Despite limited effects of busyness on a hospital level, there could still be harmful effects of local situations.

High ward occupancy, bedspacing, and 60 day mortality for patients with myocardial infarction, stroke, and heart failure.

AIMS: To study the consequences of crowded wards among patients with cardiovascular disease. METHODS AND RESULTS: This is a cohort study among 201 801 patients with 258 807 admissions who were acutely admitted for myocardial infarction (N = 107 895), stroke (N = 87 336), or heart failure (N = 63 576) to any Norwegian hospital between 2008 and 2016. The ward admitting most patients with the given clinical condition was considered a patient's home ward. We compared patients with the same condition admitted when home ward occupancy was different, at the same hospital and during comparable time periods. Occupancy was standardized such that a one-unit difference corresponded to the interquartile range in occupancy in the given month. One interquartile increase in home ward occupancy was associated with 7% higher odds of admission to an alternate ward [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.09 to 1.11], and length of stay was shorter (-0.10 days, 95% CI -0.18 to -0.09). Patients with heart failure had 15% higher odds of admission to alternate wards (OR 1.15, 95% CI 1.08 to 1.23) and increased mortality [hazard ratio (HR) 1.08, 95% CI 1.03 to 1.15]. We found no apparent effect on mortality for patients with myocardial infarction (HR 0.99, 95% CI 0.94 to 1.05) or stroke (HR 1.00, 95% CI 0.96 to 1.05). CONCLUSIONS: Patients with heart failure had higher risk of admission to alternate wards when home ward occupancy was high. These patients may be negatively affected by full wards.

High volumes of recent surgical admissions, time to surgery, and 60-day mortality.

AIMS: Few studies have investigated potential consequences of strained surgical resources. The aim of this cohort study was to assess whether a high proportion of concurrent acute surgical admissions, tying up hospital surgical capacity, may lead to delayed surgery and affect mortality for hip fracture patients. METHODS: This study investigated time to surgery and 60-day post-admission death of patients 70 years and older admitted for acute hip fracture surgery in Norway between 2008 and 2016. The proportion of hospital capacity being occupied by newly admitted surgical patients was used as the exposure. Hip fracture patients admitted during periods of high proportion of recent admissions were compared with hip fracture patients admitted at the same hospital during the same month, on similar weekdays, and times of the day with fewer admissions. RESULTS: Among 60,072 patients, mean age was 84.6 years (SD 6.8), 78% were females, and median time to surgery was 20 hours (IQR 11 to 29). Overall, 14% (8,464) were dead 60 days after admission. A high (75th percentile) proportion of recent surgical admission compared to a low (25th percentile) proportion resulted in 20% longer time to surgery (95% confidence interval (CI) 16 to 25) and 20% higher 60-day mortality (hazard ratio 1.2, 95% CI 1.1 to 1.4). CONCLUSION: A high volume of recently admitted acute surgical patients, indicating probable competition for surgical resources, was associated with delayed surgery and increased 60-day mortality. Cite this article: Bone Joint J 2021;103-B(2):264-270.

Hospitals´ Discharge Tendency and Risk of Death - An Analysis of 60,000 Norwegian Hip Fracture Patients.

PURPOSE: A reduction in the length of hospital stay may threaten patient safety. This study aimed to estimate the effect of organizational pressure to discharge on 60-day mortality among hip fracture patients. PATIENTS AND METHODS: In this cohort study, hip fracture patients were analyzed as if they were enrolled in a sequence of trials for discharge. A hospital's discharge tendency was defined as the proportion of patients with other acute conditions who were discharged on a given day. Because the hospital's tendency to discharge would affect hip fracture patients in an essentially random manner, this exposure could be regarded as analogous to being randomized to treatment in a clinical trial. The study population consisted of 59,971 Norwegian patients with hip fractures, hospitalized between 2008 and 2016, aged 70 years and older. To calculate the hospital discharge tendency for a given day, we used data from all 5,013,773 other acute hospitalizations in the study period. RESULTS: The probability of discharge among hip fracture patients increased by 5.5 percentage points (95% confidence interval (CI)=5.3-5.7) per 10 percentage points increase in hospital discharges of patients with other acute conditions. The increased risk of death that could be attributed to a discharge from organizational causes was estimated to 3.7 percentage points (95% CI=1.4-6.0). The results remained stable under different time adjustments, follow-up periods, and age cut-offs. CONCLUSION: This study showed that discharges from organizational causes may increase the risk of death among hip fracture patients.

Author Correction: Systematic assessment of prescribed medications and short-term risk of myocardial infarction - a pharmacopeia-wide association study from Norway and Sweden.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Systematic assessment of prescribed medications and short-term risk of myocardial infarction - a pharmacopeia-wide association study from Norway and Sweden.

Wholesale, unbiased assessment of Scandinavian electronic health-care databases offer a unique opportunity to reveal potentially important undiscovered drug side effects. We examined the short-term risk of acute myocardial infarction (AMI) associated with drugs prescribed in Norway or Sweden. We identified 24,584 and 97,068 AMI patients via the patient- and the cause-of-death registers and linked to prescription databases in Norway (2004-2014) and Sweden (2005-2014), respectively. A case-crossover design was used to compare the drugs dispensed 1-7 days before the date of AMI diagnosis with 15-21 days' time -window for all the drug individually while controlling the receipt of other drugs. A BOLASSO approach was used to select drugs that acutely either increase or decrease the apparent risk of AMI. We found 48 drugs to be associated with AMI in both countries. Some antithrombotics, antibiotics, opioid analgesics, adrenergics, proton-pump inhibitors, nitroglycerin, diazepam, metoclopramide, acetylcysteine were associated with higher risk for AMI; whereas angiotensin-II-antagonists, calcium-channel blockers, angiotensin-converting-enzyme inhibitors, serotonin-specific reuptake inhibitors, allopurinol, mometasone, metformin, simvastatin, levothyroxine were inversely associated. The results were generally robust in different sensitivity analyses. This study confirms previous findings for certain drugs. Based on the known effects or indications, some other associations could be anticipated. However, inverse associations of hydroxocobalamin, levothyroxine and mometasone were unexpected and needs further investigation. This pharmacopeia-wide association study demonstrates the feasibility of a systematic, unbiased approach to pharmacological triggers of AMI and other diseases with acute, identifiable onsets.

Physical Activity and the Risk of Gallbladder Disease: A Systematic Review and Meta-Analysis of Cohort Studies.

BACKGROUND: Physical activity has been hypothesized to reduce the risk of gallbladder disease (gallstones, cholecystitis, cholecystectomy); however, results from epidemiological studies have not always shown statistically significant associations. We conducted a systematic review and meta-analysis to clarify the presence and strength of an association between physical activity and gallbladder disease risk. METHODS: PubMed and Embase databases were searched for studies of physical activity and gallbladder disease up to 9th of January 2015. Prospective studies reporting relative risk (RR) estimates and 95% confidence intervals (CIs) of gallbladder disease associated with physical activity were included. Summary RRs were estimated using a random effects model. RESULTS: Eight studies including 6958 cases and 218,204 participants were included. The summary RR for the highest versus the lowest level of physical activity was 0.75 (95% CI: 0.69-0.81, n = 8) and there was no evidence of heterogeneity, I2 = 0%). In the dose-response analysis the summary relative risk per 20 MET-hours of activity was 0.85 (95% CI: 0.80-0.90, I2 = 0%, n = 2) for leisure-time physical activity, 0.83 (95% CI: 0.76-0.90, I2 = 0%, n = 2) for vigorous physical activity, and 0.86 (95% CI: 0.76-0.98, I2 = 0%, n = 2) for nonvigorous physical activity. CONCLUSION: Our analysis confirms a protective effect of physical activity on risk of gallbladder disease.

Molecular Subtypes of Breast Cancer: Long-term Incidence Trends and Prognostic Differences.

BACKGROUND: Secular trends in incidence and prognosis of molecular breast cancer subtypes are poorly described. We studied long-term trends in a population of Norwegian women born 1886-1977. METHODS: A total of 52,949 women were followed for breast cancer incidence, and 1,423 tumors were reclassified into molecular subtypes using IHC and in situ hybridization. We compared incidence rates among women born 1886-1928 and 1929-1977, estimated age-specific incidence rate ratios (IRR), and performed multiple imputations to account for unknown subtype. Prognosis was compared for women diagnosed before 1995 and in 1995 or later, estimating cumulative risk of death and HRs. RESULTS: Between 50 and 69 years of age, incidence rates of Luminal A and Luminal B (HER2-) were higher among women born in 1929 or later, compared with before 1929 [IRRs 50-54 years; after imputations: 3.5; 95% confidence interval (CI), 1.8-6.9 and 2.5; 95% CI, 1.2-5.2, respectively], with no clear differences for other subtypes. Rates of death were lower in women diagnosed in 1995 or later, compared to before 1995, for Luminal A (HR 0.4; 95% CI, 0.3-0.5), Luminal B (HER2-; HR 0.5; 95% CI, 0.3-0.7), and Basal phenotype (HR 0.4; 95% CI, 0.2-0.9). CONCLUSIONS: We found a strong secular incidence increase restricted to Luminal A and Luminal B (HER2-) subtypes, combined with a markedly improved prognosis for these subtypes and for the Basal phenotype. IMPACT: This study documents a clear secular increase in incidence and a concomitant improved prognosis for specific molecular breast cancer subtypes. Cancer Epidemiol Biomarkers Prev; 25(12); 1625-34. ©2016 AACR.