[Show abstract][Hide abstract] ABSTRACT: Although cross-sectional studies have shown a positive association between Se and cholesterol concentrations, a recent randomised controlled trial in 501 elderly UK individuals of relatively low-Se status found that Se supplementation for 6 months lowered total plasma cholesterol. The Danish PRECISE (PREvention of Cancer by Intervention with Selenium) pilot study (ClinicalTrials.gov ID: NCT01819649) was a 5-year randomised, double-blinded, placebo-controlled trial with four groups (allocation ratio 1:1:1:1). Men and women aged 60–74 years (
491) were randomised to 100 (
124), 200 (
122) or 300 (
119) μg Se-enriched yeast or matching placebo-yeast tablets (
126) daily for 5 years. A total of 468 participants continued the study for 6 months and 361 participants, equally distributed across treatment groups, continued for 5 years. Plasma samples were analysed for total and HDL-cholesterol and for total Se concentrations at baseline, 6 months and 5 years. The effect of different doses of Se supplementation on plasma lipid and Se concentrations was estimated by using linear mixed models. Plasma Se concentration increased significantly and dose-dependently in the intervention groups after 6 months and 5 years. Total cholesterol decreased significantly both in the intervention groups and in the placebo group after 6 months and 5 years, with small and nonsignificant differences in changes in plasma concentration of total cholesterol, HDL-cholesterol, non-HDL-cholesterol and total:HDL-cholesterol ratio between intervention and placebo groups. The effect of long-term supplementation with Se on plasma cholesterol concentrations or its sub-fractions did not differ significantly from placebo in this elderly population.
The British journal of nutrition 09/2015; DOI:10.1017/S0007114515003499 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although physician-rated health is emerging as a potentially useful variable in research, with implications in practice, it has not been analyzed. Moreover, one of its most important aspects, namely, concordance with patients' objective health state, has not been investigated. This study sought to measure concordance between physician-rated health and an objective health measure, and assess both measures' validity in predicting death.
The data for the study were drawn from a 1998-1999 survey and subsequent mortality follow-up of residential and nursing homes in Madrid (Spain). Study subjects were 630 residents aged ≥65 years, and their respective facility physicians. Measures included agreement between physicians' rating of residents' overall health (good, intermediate or poor) and an objective measure of residents' health (good, intermediate or poor), based on functional capacity, cognitive status, and number of chronic conditions. Overrating was defined as any case where health, rated as good by a physician, was objectively rated as poor.
Whereas 45 % of physicians and 55 % of residents rated their health as good, only 4 % of such residents had good objective health. Of those who received a physician rating of good/very good health, 39.0 % had poor objective health. There was evidence of clear overrating in 18 % of the population, and clear to moderate overrating in 73 % of the population. In terms of power to predict mortality, the pattern of behavior shown by the objective health measure was good, graded and congruent, and better than that shown by physician-rated health.
Physician overrating of the overall health of older persons in residential and nursing homes, would appear to be very high. Although some degree of contextualization by physicians in this setting might be considered reasonable, the degree of overrating in our population seems nevertheless excessive.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the association of diabetes and diabetes treatment with risk of postmenopausal breast cancer.
Histologically confirmed incident cases of postmenopausal breast (N = 916) cancer were recruited from 23 Spanish public hospitals. Population-based controls (N = 1094) were randomly selected from primary care center lists within the catchment areas of the participant hospitals. ORs (95 % CI) were estimated using mixed-effects logistic regression models, using the recruitment center as a random effect term. Breast tumors were classified into hormone receptor positive (ER+ or PR+), HER2+ and triple negative (TN).
Diabetes was not associated with the overall risk of breast cancer (OR 1.09; 95 % CI 0.82-1.45), and it was only linked to the risk of developing TN tumors: Among 91 women with TN tumors, 18.7 % were diabetic, while the corresponding figure among controls was 9.9 % (OR 2.25; 95 % CI 1.22-4.15). Regarding treatment, results showed that insulin use was more prevalent among diabetic cases (2.5 %) as compared to diabetic controls (0.7 %); OR 2.98; 95 % CI 1.26-7.01. They also showed that, among diabetics, the risk of developing HR+/HER2- tumors decreased with longer metformin use (ORper year 0.89; 95 % CI 0.81-0.99; based on 24 cases and 43 controls).
This study reinforces the need to correctly classify breast cancers when studying their association with diabetes. Given the low survival rates in women diagnosed with TN breast tumors and the potential impact of diabetes control on breast cancer prevention, more studies are needed to better characterize this association.
[Show abstract][Hide abstract] ABSTRACT: In Spain, cervical cancer prevention is based on opportunistic screening, due to the disease's traditionally low incidence and mortality rates. Changes in sexual behaviour, tourism and migration have, however, modified the probability of exposure to human papilloma virus among Spaniards. This study thus sought to evaluate recent cervical cancer mortality trends in Spain.
We used annual female population figures and individual records of deaths certified as cancer of cervix, reclassifying deaths recorded as unspecified uterine cancer to correct coding quality problems. Joinpoint models were fitted to estimate change points in trends, as well as the annual (APC) and average annual percentage change. Log-linear Poisson models were also used to study age-period-cohort effects on mortality trends and their change points.
1981 marked the beginning of a decline in cervical cancer mortality (APC1981-2003: -3.2; 95%CI:-3.4;-3.0) that ended in 2003, with rates reaching a plateau in the last decade (APC2003-2012: 0.1; 95%CI:-0.9; 1.2). This trend, which was observable among women aged 45-46 years (APC2003-2012:1.4; 95%CI:-0.1;2.9) and over 65 years (APC2003-2012:-0.1; 95%CI:-1.9;1.7), was clearest in Spain's Mediterranean and Southern regions.
The positive influence of opportunistic screening is not strong enough to further reduce cervical cancer mortality rates in the country. Our results suggest that the Spanish Health Authorities should reform current prevention programmes and surveillance strategies in order to confront the challenges posed by cervical cancer.
BMC Cancer 04/2015; 15(1):287. DOI:10.1186/s12885-015-1306-x · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AimsA systematic review and meta-analysis were conducted to synthesize results from cohort studies on initiation into drug injection among vulnerable populations, to quantify heterogeneity in the estimated incidence rates of drug injection, and to identify potential sources of heterogeneity and bias.MethodsMEDLINE, EMBASE, PsycINFO, and LILACS were searched for relevant studies published between 1980 and 2012. Investigators independently reviewed studies for inclusion, retrieved information on baseline population characteristics and follow-up features, and assessed study quality. Study-specific incidence rates of drug injection were calculated as the number of new injectors divided by the person-years at risk. The I2 statistic was used to quantify heterogeneity in incidence rates across studies, and random-effects meta-regression models were used to identify determinants of heterogeneity and bias.ResultsNine cohorts totaling 1,843 participants met the inclusion criteria, with individual sample sizes of 70 to 415 participants and follow-up lengths of 0.5 to 3.4 years. The incidence of drug injection varied widely from 2.1 to 24.2 cases per 100 person-years. The strong between-study heterogeneity (I2=90%, P<0.001) was significantly reduced after accounting for the different follow-up lengths (I2=17%, P=0.30), with a 57% (95% confidence interval 46–66%) decrease in the pooled incidence of drug injection per one-year increase in average follow-up.Conclusions
The incidence of drug injection decreases sharply with increasing follow-up length in cohort studies on drug injection initiation. Low retention rates and potential for downward selection bias in cohort studies on drug injection initiation are caused primarily by greater loss to follow-up among individuals at higher risk of starting injection, compared with other participants. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To examine the longitudinal association between age and intraocular pressure (IOP) in a large sample of Korean men and women.
We conducted a prospective cohort study of 274,064 young and middle-aged Korean adults with normal fundoscopic findings, following them from January 1, 2002, to February 28, 2010. Health exams were scheduled annually or biennially. At each visit, IOP was measured in both eyes using automated noncontact tonometers. The longitudinal change in IOP with age was evaluated using three-level mixed models for longitudinal paired-eye data, accounting for correlations between paired eyes and repeated measurements over time.
In fully adjusted models, the average longitudinal change in IOP per 1-year increase in age was -0.065 mm Hg (95% confidence interval [CI] -0.068 to -0.063), with marked sex differences (P < 0.001). In men, the average annual IOP change was -0.093 mm Hg (95% CI -0.096 to -0.091) throughout follow-up. In women, the average annual IOP change was -0.006 mm Hg (95% CI -0.010 to -0.003), with a relatively flat association in the age range of 30 to 59 years and more marked annual decreases at younger and older ages.
Intraocular pressure was inversely associated with age in a large cohort of Korean adults attending health-screening visits. For men, this inverse association was observed throughout the entire age range, while for women it was evident only in younger (<30 years of age) and older (≥60 years of age) women, with no association in women aged 30 to 59. Further research is needed to better understand the underlying mechanisms and to reconsider cutoffs for defining high IOP by age and sex groups in Asian populations.
[Show abstract][Hide abstract] ABSTRACT: Objective:
Overt and subclinical hypothyroidism are risk factors for atherosclerosis. It is unclear whether thyroid hormone levels within the normal range are also associated with atherosclerosis measured by coronary artery calcium (CAC).
Approach and results:
We conducted a cross-sectional study of 41 403 apparently healthy young and middle-aged men and women with normal thyroid hormone levels. Free thyroxin, free triiodothyronine, and thyroid-stimulating hormone levels were measured by electrochemiluminescent immunoassay. CAC score was measured by multidetector computed tomography. The multivariable adjusted CAC ratios comparing the highest versus the lowest quartile of thyroid hormones were 0.74 (95% confidence interval, 0.60-0.91; P for trend <0.001) for free thyroxin, 0.81 (0.66-1.00; P for trend=0.05) for free triiodothyronine, and 0.78 (0.64-0.95; P for trend=0.01) for thyroid-stimulating hormone. Similarly, the odds ratios for detectable CAC (CAC >0) comparing the highest versus the lowest quartiles of thyroid hormones were 0.87 (0.79-0.96; P for linear trend <0.001) for free thyroxin, 0.90 (0.82-0.99; P for linear trend=0.02) for free triiodothyronine, and 0.91 (0.83-1.00; P for linear trend=0.03) for thyroid-stimulating hormone.
In a large cohort of apparently healthy young and middle-aged euthyroid men and women, low-normal free thyroxin and thyroid-stimulating hormone were associated with a higher prevalence of subclinical coronary artery disease and with a greater degree of coronary calcification.
[Show abstract][Hide abstract] ABSTRACT: Background:
Overt and subclinical hypothyroidism are associated with higher levels of serum creatinine and with increased risk of chronic kidney disease (CKD). The prospective association between thyroid hormones and kidney function in euthyroid individuals,however, is largely unexplored.
We conducted a prospective cohort study in 104 633 South Korean men and women who were free of CKD and proteinuria at baseline and had normal thyroid hormone levels and no history of thyroid disease or cancer. At each annual or biennial follow-up visit, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxin (FT4) levels were measured by radioimmunoassay. The study outcome was incident CKD, defined as an estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2 based on the Chronic Kidney Disease Epidemiology Collaboration creatinine equation.
After a median follow-up of 3.5 years, 1032 participants developed incident CKD.There was a positive association between high-normal levels of TSH and increased risk of incident CKD. In fully-adjusted models including baseline eGFR, the hazard ratio comparing the highest vs the lowest quintiles of TSH was 1.26 [95% confidence interval (CI) 1.02 to 1.55; P for linear trend=0.03]. In spline models, FT3 levels below 3 pg/ml were also associated with increased risk of incident CKD. There was no association between FT4 levels and CKD.
In a large cohort of euthyroid men and women, high levels of TSH and low levels of FT3, even within the normal range, were modestly associated with an increased risk of incident CKD.
International Journal of Epidemiology 07/2014; 43(5). DOI:10.1093/ije/dyu126 · 9.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although oral cavity, pharyngeal, oesophageal and gastric cancers share some risk factors, no comparative analysis of mortality rate trends in these illnesses has been undertaken in Spain. This study aimed to evaluate the independent effects of age, death period and birth cohort on the mortality rates of these tumours.
Specific and age-adjusted mortality rates by tumour and sex were analysed. Age-period-cohort log-linear models were fitted separately for each tumour and sex, and segmented regression models were used to detect changes in period- and cohort-effect curvatures.
Among men, the period-effect curvatures for oral cavity/pharyngeal and oesophageal cancers displayed a mortality trend that rose until 1995 and then declined. Among women, oral cavity/pharyngeal cancer mortality increased throughout the study period whereas oesophageal cancer mortality decreased after 1970. Stomach cancer mortality decreased in both sexes from 1965 onwards. Lastly, the cohort-effect curvature showed a certain degree of similarity for all three tumours in both sexes, which was greater among oral cavity, pharyngeal and oesophageal cancers, with a change point in evidence, after which risk of death increased in cohorts born from the 1910-1920s onwards and decreased among the 1950-1960 cohorts and successive generations. This latter feature was likewise observed for stomach cancer.
While the similarities of the cohort effects in oral cavity/pharyngeal, oesophageal and gastric tumours support the implication of shared risk factors, the more marked changes in cohort-effect curvature for oral cavity/pharyngeal and oesophageal cancer could be due to the greater influence of some risk factors in their aetiology, such as smoking and alcohol consumption. The increase in oral cavity/pharyngeal cancer mortality in women deserves further study.
BMC Cancer 04/2014; 14(1):254. DOI:10.1186/1471-2407-14-254 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In contrast to other haematological cancers, mortality from non-Hodgkin's lymphoma and multiple myeloma increased dramatically during the second half of the 20th century in most developed countries. This widespread upward trend remains controversial, as it may be attributable either to progressive improvements in diagnosis and certification or to increasing exposures to little-known but relevant risk factors.
To assess the relative contribution of these factors, we analysed the independent effects of age, death period, and birth cohort on haematological cancer mortality rates in Spain across the period 1952-2006. Weighted joinpoint regression analyses were performed to detect and estimate changes in period and cohort curvatures.
Although mortality rates were consistently higher among men, trends across periods and cohorts were virtually identical in both sexes. There was an early period trend reversal in the 1960s for Hodgkin's disease and leukaemia, which was delayed to the 1980s for multiple myeloma and the 1990s for non-Hodgkin's lymphoma. Birth cohort patterns showed a first downturn for generations born in the 1900s and 1910s for all haematological cancers, and a second trend reversal for more recent cohorts born in the 1950s and 1960s for non-Hodgkin's lymphoma and leukaemia.
The sustained decline in Hodgkin's disease mortality and the levelling off in leukaemia seem to be driven by an early period effect linked to improvements in disease treatment, whereas the steep upward trends in non-Hodgkin's lymphoma and multiple myeloma mortality in Spain are more likely explained by a cohort effect linked to better diagnosis and death certification in the elderly. The consistent male excess mortality across all calendar periods and age groups points to the importance of possible sex-related genetic markers of susceptibility in haematological cancers.
BMC Cancer 04/2014; 14(1):250. DOI:10.1186/1471-2407-14-250 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Context: Hyperthyroidism and hypothyroidism, both overt and subclinical, are associated with all-cause and cardiovascular mortality. The association between thyroid hormones and mortality in euthyroid individuals, however, is unclear. Objective: To examine the prospective association between thyroid hormones levels within normal ranges and mortality endpoints. Design: Prospective cohort study from January 1, 2002 to December 31, 2009. Participants: 212,456 middle age South Korean men and women who had normal thyroid hormone levels and no history of thyroid disease at baseline. Exposures: Free thyroxin (FT4), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) levels were measured by radioimmunoassay. Main outcomes: Vital status and cause of death ascertainment were based on linkage to the National Death Index death certificate records. Results: After a median follow-up of 4.3 years, 730 participants died (335 cancer deaths and 112 cardiovascular deaths). FT4 was inversely associated with all-cause mortality (HR = 0.77, 95% CI 0.63 to 0.95, comparing the highest vs. lowest quartile of FT4; P for linear trend = 0.01), and FT3 was inversely associated cancer mortality (HR = 0.62, 95% CI 0.45 to 0.85; P for linear trend = 0.001). TSH was not associated with mortality endpoints. Conclusions: In a large cohort of euthyroid men and women, FT4 and FT3 levels within the normal range were inversely associated with the risk of all-cause mortality and cancer mortality, particularly liver cancer mortality.
The Journal of Clinical Endocrinology and Metabolism 04/2014; 99(7):jc20133832. DOI:10.1210/jc.2013-3832 · 6.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: World-wide controversy continues to surround the question of whether exposure to ionising radiations arising from nuclear power plants and radioactive fuel cycle facilities could increase the risk of cancer. The objective was to analyse cancer mortality in towns close to Spanish nuclear power plants and radioactive fuel cycle facilities by reference to their history of exposure to artificial radiation generated by such emissions. An ecological cancer mortality study was conducted to know the effect of artificial radiation, estimated taken into account the magnitude of emissions, in towns ≤30 km of any installation.
A model of atmospheric and aquatic dispersion of radionuclides was used. As reference, towns within a 50–100 km radius were matched with exposed by socio-demographic characteristics. For analysis purposes, log-linear Poisson models were fitted. The cumulative effective dose was the measure of exposure. Mortality rates ratios were calculated for each tumour site. Natural radiation and socio-demographic matching variables were included in the models, with ‘installation’ as a random effects term. The estimated cumulative artificial radiation dose was below 350 μSv for all sites. For nuclear power plants overall, analysis showed no positive association with increases in the cumulative dose. In the joint analysis of radioactive fuel cycle facilities, however, mortality was observed to rise with increases in the estimated radiation dose in the case of lung, bone and colorectal cancer, and in breast cancer among women. These results would not appear to be due to exposure arising from the operation of the installations, since were not reproduced around installations of the same type.
International journal of Environmental Science and Technology 02/2014; 11(1). DOI:10.1007/s13762-013-0223-2 · 2.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A total of 2,514,346 metric tons (Mt) of asbestos were imported into Spain from 1906 until the ban on asbestos in 2002. Our objective was to study pleural cancer mortality trends as an indicator of mesothelioma mortality and update mortality predictions for the periods 2011--2015 and 2016--2020 in Spain.
Log-linear Poisson models were fitted to study the effect of age, period of death and birth cohort (APC) on mortality trends. Change points in cohort- and period-effect curvatures were assessed using segmented regression. Fractional power-link APC models were used to predict mortality until 2020. In addition, an alternative model based on national asbestos consumption figures was also used to perform long-term predictions.
Pleural cancer deaths increased across the study period, rising from 491 in 1976--1980 to 1,249 in 2006--2010. Predictions for the five-year period 2016--2020 indicated a total of 1,319 pleural cancer deaths (264 deaths/year). Forecasts up to 2020 indicated that this increase would continue, though the age-adjusted rates showed a levelling-off in male mortality from 2001 to 2005, corresponding to the lower risk in post-1960 generations. Among women, rates were lower and the mortality trend was also different, indicating that occupational exposure was possibly the single factor having most influence on pleural cancer mortality.
The cancer mortality-related consequences of human exposure to asbestos are set to persist and remain in evidence until the last surviving members of the exposed cohorts have disappeared. It can thus be assumed that occupationally-related deaths due to pleural mesothelioma will continue to occur in Spain until at least 2040.
BMC Cancer 11/2013; 13(1):528. DOI:10.1186/1471-2407-13-528 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The intervention program for autism known as Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH) is considered an emerging practice for autism. In the present study we used state-of-the-art meta-analytical procedures to examine the pooled clinical effects of TEACCH in a variety of outcomes. A total of 13 studies were selected for meta-analysis totaling 172 individuals with autism exposed to TEACCH. Standardized measures of perceptual, motor, adaptive, verbal and cognitive skills were identified as treatment outcomes. We used inverse-variance weighted random effects meta-analysis supplemented with quality assessment, sensitivity analysis, meta-regression, and heterogeneity and publication bias tests. The results suggested that TEACCH effects on perceptual, motor, verbal and cognitive skills were of small magnitude in the meta-analyzed studies. Effects over adaptive behavioral repertoires including communication, activities of daily living, and motor functioning were within the negligible to small range. There were moderate to large gains in social behavior and maladaptive behavior. The effects of the TEACCH program were not moderated by aspects of the intervention such as duration (total weeks), intensity (hours per week), and setting (home-based vs. center-based). While the present meta-analysis provided limited support for the TEACCH program as a comprehensive intervention, our results should be considered exploratory owing to the limited pool of studies available.
[Show abstract][Hide abstract] ABSTRACT: Little is known about the dose-response relationship between physical activity and health benefits among young people. Our objective was to analyse the association between the frequency of undertaking moderate-to-vigorous physical activity (MVPA) and the self-reported health status of the adolescent population.
All regions of Spain.
Students aged 11-18 years participating in the Spanish Health Behaviour in School-aged Children survey 2006. A total of 375 schools and 21 188 students were selected.
The frequency of undertaking MVPA was measured by a questionnaire, with the following four health indicators: self-rated health, health complaints, satisfaction with life and health-related quality of life. Linear and logistic regression models were used to analyse the association, adjusting for potential confounding variables and the modelling of the dose-response relationship.
As the frequency of MVPA increased, the association with health benefits was stronger. A linear trend (p<0.05) was found for self-rated health and health complaints in males and females and for satisfaction with life among females; for health-related quality of life this relationship was quadratic for both sexes (p<0.05). For self-reported health and health complaints, the effect was found to be of greater magnitude in males than in females and, in all scales, the benefits were observed from the lowest frequencies of MVPA, especially in males.
A protective effect of MVPA was found in both sexes for the four health indicators studied, and this activity had a gradient effect. Among males, health benefits were detected from very low levels of physical activity and the magnitude of the relationship was greater than that for females.
BMJ Open 05/2013; 3(5). DOI:10.1136/bmjopen-2013-002644 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Gail model for predicting the absolute risk of invasive breast cancer has been validated extensively in US populations, but its performance in the international setting remains uncertain. We evaluated the predictive accuracy of the Gail model in 54,649 Spanish women aged 45–68 years who were free of breast cancer at the 1996–1998 baseline mammographic examination in the population-based Navarre Breast Cancer Screening Program. Incident cases of invasive breast cancer and competing deaths were ascertained until the end of 2005 (average follow-up of 7.7 years) through linkage with population-based cancer and mortality registries. The Gail model was tested for calibration and discrimination in its original form and after recalibration to the lower breast cancer incidence and risk factor prevalence in the study cohort, and compared through cross-validation with a Navarre model fully developed from this cohort. The original Gail model overpredicted significantly the 835 cases of invasive breast cancer observed in the cohort (ratio of expected to observed cases 1.46, 95 % CI 1.36–1.56). The recalibrated Gail model was well calibrated overall (expected-to-observed ratio 1.00, 95 % CI 0.94–1.07), but it tended to underestimate risk for women in low-risk quintiles and to overestimate risk in high-risk quintiles (P = 0.01). The Navarre model showed good cross-validated calibration overall (expected-to-observed ratio 0.98, 95 % CI 0.92–1.05) and in different cohort subsets. The Navarre and Gail models had modest cross-validated discrimination indexes of 0.542 (95 % CI 0.521–0.564) and 0.544 (95 % CI 0.523–0.565), respectively. Although the original Gail model cannot be applied directly to populations with different underlying rates of invasive breast cancer, it can readily be recalibrated to provide unbiased estimates of absolute risk in such populations. Nevertheless, its limited discrimination ability at the individual level highlights the need to develop extended models with additional strong risk factors.
Electronic supplementary material
The online version of this article (doi:10.1007/s10549-013-2428-y) contains supplementary material, which is available to authorized users.
Breast Cancer Research and Treatment 02/2013; 138(1). DOI:10.1007/s10549-013-2428-y · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction
It is not clear whether high mammographic density (MD) is equally associated with all subtypes of breast cancer (BC). We investigated the association between MD and subsequent BC, considering invasiveness, means of detection, pathologic subtype, and the time elapsed since mammographic exploration and BC diagnosis.
BC cases occurring in the population of women who attended screening from 1997 through 2004 in Navarre, a Spanish region with a fully consolidated screening program, were identified via record linkage with the Navarre Cancer Registry (n = 1,172). Information was extracted from the records of their first attendance at screening in that period. For each case, we randomly selected four controls, matched by screening round, year of birth, and place of residence. Cases were classified according to invasiveness (ductal carcinoma in situ (DCIS) versus invasive tumors), pathologic subtype (considering hormonal receptors and HER2), and type of diagnosis (screen-detected versus interval cases). MD was evaluated by a single, experienced radiologist by using a semiquantitative scale. Data on BC risk factors were obtained by the screening program in the corresponding round. The association between MD and tumor subtype was assessed by using conditional logistic regression.
MD was clearly associated with subsequent BC. The odds ratio (OR) for the highest MD category (MD >75%) compared with the reference category (MD <10%) was similar for DCIS (OR = 3.47; 95% CI = 1.46 to 8.27) and invasive tumors (OR = 2.95; 95% CI = 2.01 to 4.35). The excess risk was particularly high for interval cases (OR = 7.72; 95% CI = 4.02 to 14.81) in comparison with screened detected tumors (OR = 2.17; 95% CI = 1.40 to 3.36). Sensitivity analyses excluding interval cases diagnosed in the first year after MD assessment or immediately after an early recall to screening yielded similar results. No differences were seen regarding pathologic subtypes. The excess risk associated with MD persisted for at least 7 to 8 years after mammographic exploration.
Our results confirm that MD is an important risk factor for all types of breast cancer. High breast density strongly increases the risk of developing an interval tumor, and this excess risk is not completely explained by a possible masking effect.
Breast cancer research: BCR 01/2013; 15(1):R9. DOI:10.1186/bcr3380 · 5.49 Impact Factor