Vaginal health, endometrial thickness and changes in bone markers in postmenopausal women after 6 months of treatment with ospemifene in real clinical practice.

OBJECTIVE: To assess vaginal health, endometrial thickness, and changes in bone markers in postmenopausal women with vulvovaginal atrophy (VVA) treated with 60 mg/day of ospemifene under routine clinical practice. METHODS: The AYSEX study is a Spanish observational and prospective study performed in one center in which 5 gynecologists recruited postmenopausal women with VVA in routine clinical practice treated continuously with ospemifene 60 mg/day for 12 months as an appropriate therapeutic option. This article refers to the 3- and 6-months analysis. Vaginal health was assessed by pH and using Vaginal Health Index (VHI) at baseline and 3 months later. Endometrial thickness, measured by vaginal ultrasonography, and bone resorption marker (CTx) were assessed at baseline and 6 months later. RESULTS: A total of 100 postmenopausal women cytologically and clinically diagnosed with VVA were included in the study. After 3 months of treatment with ospemifene, pH improved from 6.1 to 4.5 (p < .0001), and VHI improved from 10 to 19 points (p < .0001). The percentage of patients with VVA according to VHI decreased from 100% to 5.2% (p < .0001). After 6 months, mean CTx levels decreased from 0.42 pg/ml at baseline to 0.37 pg/ml 6 months later (p = .0018), and mean endometrial thickness changed from 2.24 to 2.15 mm (p = .6066). CONCLUSIONS: Up to date, this is the only prospective and observational study with ospemifene in routine clinical practice conditions and confirms the results previously reported from randomized controlled clinical trials, improving VVA, not increasing endometrial thickness, and decreasing CTx levels by exerting an anti-resorptive function.

Ospemifene in clinical practice for vulvo-vaginal atrophy: results at 3 months of follow-up of use.

OBJECTIVE: To assess the effect of ospemifene 60 mg/day in vulvovaginal atrophy (VVA) in postmenopausal women under conditions of routine clinical practice after 3 months of follow-up. METHODS: The AYSEX study is a Spanish observational, prospective, and unicentric study in which 5 gynecologists recruited postmenopausal women with VVA in routine clinical practice treated with ospemifene 60 mg/day as an appropriate therapeutic option. Vaginal health, sexual health, dryness, dyspareunia, quality of life, and satisfaction with treatment were assessed at baseline and after three months using validated scales. RESULTS: A total of 100 postmenopausal women cytologically and clinically diagnosed with VVA were included in the study. After 3 months of treatment with ospemifene, vaginal health index increased and vaginal pH, dryness, and dyspareunia decreased significantly (p < .0001). A significant improvement was observed in sexual function and quality of life. CONCLUSIONS: This study in routine clinical practice conditions confirms the results previously reported by randomized controlled trials, including a significant improvement in VVA, sexual function, quality of life, and satisfaction with the treatment.

Prevalence of healthy lifestyles against cancer in Spanish women.

Modifying behavior towards healthier lifestyles could prevent a significant number of malignant tumors. We evaluated the prevalence of healthy habits against cancer in Spanish women free of this disease, taking as a reference the recommendations for cancer prevention included in the European Code Against Cancer (ECAC), and we explored the characteristics associated with it. Our population comprised 3,584 women recruited in a population-based cross-sectional study carried out in 7 breast cancer screening programs. Information was directly surveyed and used to calculate a score based on ECAC recommendations referred to bodyweight, physical activity, diet, breastfeeding, tobacco, alcohol and hormone replacement therapy use. The degree of adherence was estimated with a score that evaluated null (0 points), partial (0.5 points) and full adherence (1 point) of each specific recommendation. Associations were explored using binary and ordinal logistic regression models. The median score was 5.7 out of 9 points. Recommendations with lower adherence were those related to intake of red/processed meat and foods high in salt (23% of total adherence), physical activity (24%) and body weight (29%), and recommendations with greater adherence where those related to hormone replacement therapy use (91%), vegetable intake (84%), alcohol (83%) and tobacco (61%). Overall adherence was better among older women, parous women, and in those living in rural areas, and worse among women with higher caloric intake. These recommendations should be evaluated periodically. Screening programs can be an appropriate place to disseminate this information.

Overeating, caloric restriction and mammographic density in Spanish women. DDM-Spain study.

OBJECTIVES: Mammographic density (MD) is a strong risk factor for breast cancer. The present study evaluates the association between relative caloric intake and MD in Spanish women. STUDY DESIGN: We conducted a cross-sectional study in which 3517 women were recruited from seven breast cancer screening centers. MD was measured by an experienced radiologist using craniocaudal mammography and Boyd's semi-quantitative scale. Information was collected through an epidemiological survey. Predicted calories were calculated using linear regression models, including the basal metabolic rate and physical activity as explanatory variables. Overeating and caloric restriction were defined taking into account the 99% confidence interval of the predicted value. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using center-specific mixed ordinal logistic regression models, adjusted for age, menopausal status, body mass index, parity, tobacco use, family history of breast cancer, previous biopsies, age at menarche and adherence to a Western diet. MAIN OUTCOME MEASURE: Mammographic density. RESULTS: Those women with an excessive caloric intake (>40% above predicted) presented higher MD (OR = 1.41, 95%CI = 0.97-2.03; p = 0.070). For every 20% increase in relative caloric consumption the probability of having higher MD increased by 5% (OR = 1.05, 95%CI = 0.98-1.14; p = 0.178), not observing differences between the categories of explanatory variables. Caloric restriction was not associated with MD in our study. CONCLUSIONS: This is the first study exploring the association between MD and the effect of caloric deficit or excessive caloric consumption according to the energy requirements of each woman. Although caloric restriction does not seem to affect breast density, a caloric intake above predicted levels seems to increase this phenotype.

Occupational exposures and mammographic density in Spanish women.

OBJECTIVES: The association between occupational exposures and mammographic density (MD), a marker of breast cancer risk, has not been previously explored. Our objective was to investigate the influence of occupational exposure to chemical, physical and microbiological agents on MD in adult women. METHODS: This is a population-based cross-sectional study based on 1476 female workers aged 45-65 years from seven Spanish breast cancer screening programmes. Occupational history was surveyed by trained staff. Exposure to occupational agents was assessed using the Spanish job-exposure matrix MatEmESp. Percentage of MD was measured by two radiologists using a semiautomatic computer tool. The association was estimated using mixed log-linear regression models adjusting for age, education, body mass index, menopausal status, parity, smoking, alcohol intake, type of mammography, family history of breast cancer and hormonal therapy use, and including screening centre and professional reader as random effects terms. RESULTS: Although no association was found with most of the agents, women occupationally exposed to perchloroethylene (eß=1.51; 95% CI 1.04 to 2.19), ionising radiation (eß=1.23; 95% CI 0.99 to 1.52) and mould spores (eß=1.44; 95% CI 1.01 to 2.04) tended to have higher MD. The percentage of density increased 12% for every 5 years exposure to perchloroethylene or mould spores, 11% for every 5 years exposure to aliphatic/alicyclic hydrocarbon solvents and 3% for each 5 years exposure to ionising radiation. CONCLUSIONS: Exposure to perchloroethylene, ionising radiation, mould spores or aliphatic/alicyclic hydrocarbon solvents in occupational settings could be associated with higher MD. Further studies are needed to clarify the accuracy and the reasons for these findings.

Occupation and mammographic density: A population-based study (DDM-Occup).

INTRODUCTION: High mammographic density is one of the main risk factors for breast cancer. Although several occupations have been associated with breast cancer, there are no previous occupational studies exploring the association with mammographic density. Our objective was to identify occupations associated with high mammographic density in Spanish female workers. METHODS: We conducted a population-based cross-sectional study of occupational determinants of high mammographic density in Spain, based on 1476 women, aged 45-68 years, recruited from seven screening centers within the Spanish Breast Cancer Screening Program network. Reproductive, family, personal, and occupational history data were collected. The latest occupation of each woman was collected and coded according to the 1994 National Classification of Occupations. Mammographic density was assessed from the cranio-caudal mammogram of the left breast using a semi-automated computer-assisted tool. Association between mammographic density and occupation was evaluated by using mixed linear regression models, using log-transformed percentage of mammographic density as dependent variable. Models were adjusted for age, body mass index, menopausal status, parity, smoking, alcohol intake, educational level, type of mammography, first-degree relative with breast cancer, and hormonal replacement therapy use. Screening center and professional reader were included as random effects terms. RESULTS: Mammographic density was higher, although non-statistically significant, among secondary school teachers (eß = 1.41; 95%CI = 0.98-2.03) and nurses (eß = 1.23; 95%CI = 0.96-1.59), whereas workers engaged in the care of people (eß = 0.81; 95%CI = 0.66-1.00) and housewives (eß = 0.87; 95%CI = 0.79-0.95) showed an inverse association with mammographic density. A positive trend for every 5 years working as secondary school teachers was also detected (p-value = 0.035). CONCLUSIONS: Nurses and secondary school teachers were the occupations with the highest mammographic density in our study, showing the latter a positive trend with duration of employment. Future studies are necessary to confirm if these results are due to chance or are the result of a true association whose causal hypothesis is, for the moment, unknown.

Thyroid disorders and mammographic density in Spanish women: Var-DDM study.

OBJECTIVES: The association between breast cancer (BC) and thyroid disorders has been widely explored with unclear results. Mammographic density (MD) is one of the strongest risk factor for BC. This study explores the relationship between thyroid diseases and MD in Spanish women. MATERIALS & METHODS: This cross-sectional study covered 2883 women aged 47-71 years participating in 7 BC screening programs in 2010. They allowed access to their mammograms, had anthropometrical-measures taken, and answered a telephonic epidemiological interview which included specific questions on thyroid diseases. Percentage of MD was assessed with a semiautomatic-computer tool (DM-scan) by two trained radiologists. We calculated the geometric mean of MD percentages (mean MD). Multivariable mixed linear regression models with random screening-center-specific intercepts were fitted, using log-transformed percentage of MD as dependent variable and adjusting for age, body mass index, menopausal status and other confounders. eß represents the relative increase of mean MD. RESULTS: 13.9% of the participants reported personal history of thyroid disease. MD was not associated to hyperthyroidism (eß:1.05, 95%CI: 0.82-1.36), hypothyroidism (eß:1.02, 95%CI: 0.75-1.38), thyroid nodules (eß:1.01, 95%CI: 0.85-1.19) or thyroid cancer (eß:1.03, 95%CI: 0.56-1.92). However, women with goiter had lower MD (mean MDno-goiter: 13.4% vs mean MDgoiter: 10.6%; eß:0.79, 95%CI: 0.64-0.98) and those with Hashimoto thyroiditis had higher MD (mean MDno-thyroiditis: 13.3% vs mean MDthyroidits: 25.8%; eß:1.94, 95%CI: 1.00-3.77). CONCLUSION: Functional thyroid disorders were not related to MD. However, MD was lower in women with goiter and higher in those reporting Hashimoto's thyroiditis. These relationships should be confirmed in future studies.

Sleep patterns, sleep disorders and mammographic density in spanish women: The DDM-Spain/Var-DDM study.

We explored the relationship between sleep patterns and sleep disorders and mammographic density (MD), a marker of breast cancer risk. Participants in the DDM-Spain/var-DDM study, which included 2878 middle-aged Spanish women, were interviewed via telephone and asked questions on sleep characteristics. Two radiologists assessed MD in their left craneo-caudal mammogram, assisted by a validated semiautomatic-computer tool (DM-scan). We used log-transformed percentage MD as the dependent variable and fitted mixed linear regression models, including known confounding variables. Our results showed that neither sleeping patterns nor sleep disorders were associated with MD. However, women with frequent changes in their bedtime due to anxiety or depression had higher MD (eß:1.53;95%CI:1.04-2.26).

High Mammographic Density in Long-Term Night-Shift Workers: DDM-Spain/Var-DDM.

Background: Night-shift work (NSW) has been suggested as a possible cause of breast cancer, and its association with mammographic density (MD), one of the strongest risk factors for breast cancer, has been scarcely addressed. This study examined NSW and MD in Spanish women.Methods: The study covered 2,752 women aged 45-68 years recruited in 2007-2008 in 7 population-based public breast cancer screening centers, which included 243 women who had performed NSW for at least one year. Occupational data and information on potential confounders were collected by personal interview. Two trained radiologist estimated the percentage of MD assisted by a validated semiautomatic computer tool (DM-scan). Multivariable mixed linear regression models with random screening center-specific intercepts were fitted using log-transformed percentage of MD as the dependent variable and adjusting by known confounding variables.Results: Having ever worked in NSW was not associated with MD [Formula: see text]:0.96; 95% confidence interval (CI), 0.86-1.06]. However, the adjusted geometric mean of the percentage of MD in women with NSW for more than 15 years was 25% higher than that of those without NSW history (MD>15 years:20.7% vs. MDnever:16.5%;[Formula: see text]:1.25; 95% CI,1.01-1.54). This association was mainly observed in postmenopausal participants ([Formula: see text]:1.28; 95% CI, 1.00-1.64). Among NSW-exposed women, those with ≤2 night-shifts per week had higher MD than those with 5 to 7 nightshifts per week ([Formula: see text]:1.42; 95% CI, 1.10-1.84).Conclusions: Performing NSW was associated with higher MD only in women with more than 15 years of cumulated exposure. These findings warrant replication in futures studies.Impact: Our findings suggest that MD could play a role in the pathway between long-term NSW and breast cancer. Cancer Epidemiol Biomarkers Prev; 26(6); 905-13. ©2017 AACR.

Association Between Western and Mediterranean Dietary Patterns and Mammographic Density.

OBJECTIVE: To examine the association between two dietary patterns (Western and Mediterranean), previously linked to breast cancer risk, and mammographic density. METHODS: This cross-sectional study included 3,584 women attending population-based breast cancer screening programs and recruited between October 7, 2007, and July 14, 2008 (participation rate 74.5%). Collected data included anthropometric measurements; demographic, obstetric, and gynecologic characteristics; family and personal health history; and diet in the preceding year. Mammographic density was blindly assessed by a single radiologist and classified into four categories: less than 10%, 10-25%, 25-50%, and greater than 50%. The association between adherence to either a Western or a Mediterranean dietary pattern and mammographic density was explored using multivariable ordinal logistic regression models with random center-specific intercepts. Models were adjusted for age, body mass index, parity, menopause, smoking, family history, hormonal treatment, and calorie and alcohol intake. Differences according to women's characteristics were tested including interaction terms. RESULTS: Women with a higher adherence to the Western dietary pattern were more likely to have high mammographic density (n=242 [27%]) than women with low adherence (n=169 [19%]) with a fully adjusted odds ratio (ORQ4vsQ1) of 1.25 (95% confidence interval [CI] 1.03-1.52). This association was confined to overweight-obese women (adjusted ORQ4vsQ1 [95% CI] 1.41 [1.13-1.76]). No association between Mediterranean dietary pattern and mammographic density was observed. CONCLUSION: The Western dietary pattern was associated with increased mammographic density among overweight-obese women. Our results might inform specific dietary recommendations for women with high mammographic density.

Reproducibility of data-driven dietary patterns in two groups of adult Spanish women from different studies.

The objective of the present study was to assess the reproducibility of data-driven dietary patterns in different samples extracted from similar populations. Dietary patterns were extracted by applying principal component analyses to the dietary information collected from a sample of 3550 women recruited from seven screening centres belonging to the Spanish breast cancer (BC) screening network (Determinants of Mammographic Density in Spain (DDM-Spain) study). The resulting patterns were compared with three dietary patterns obtained from a previous Spanish case-control study on female BC (Epidemiological study of the Spanish group for breast cancer research (GEICAM: grupo Español de investigación en cáncer de mama)) using the dietary intake data of 973 healthy participants. The level of agreement between patterns was determined using both the congruence coefficient (CC) between the pattern loadings (considering patterns with a CC≥0·85 as fairly similar) and the linear correlation between patterns scores (considering as fairly similar those patterns with a statistically significant correlation). The conclusions reached with both methods were compared. This is the first study exploring the reproducibility of data-driven patterns from two studies and the first using the CC to determine pattern similarity. We were able to reproduce the EpiGEICAM Western pattern in the DDM-Spain sample (CC=0·90). However, the reproducibility of the Prudent (CC=0·76) and Mediterranean (CC=0·77) patterns was not as good. The linear correlation between pattern scores was statistically significant in all cases, highlighting its arbitrariness for determining pattern similarity. We conclude that the reproducibility of widely prevalent dietary patterns is better than the reproducibility of more population-specific patterns. More methodological studies are needed to establish an objective measurement and threshold to determine pattern similarity.

Genome wide association study identifies a novel putative mammographic density locus at 1q12-q21.

Mammographic density (MD) is an intermediate phenotype for breast cancer. Previous studies have identified genetic variants associated with MD; however, much of the genetic contribution to MD is unexplained. We conducted a two-stage genome-wide association analysis among the participants in the "Determinants of Density in Mammographies in Spain" study, together with a replication analysis in women from the Australian MD Twins and Sisters Study. Our discovery set covered a total of 3,351 Caucasian women aged 45 to 68 years, recruited from Spanish breast cancer screening centres. MD was blindly assessed by a single reader using Boyd's scale. A two-stage approach was employed, including a feature selection phase exploring 575,374 SNPs in 239 pairs of women with extreme phenotypes and a verification stage for the 183 selected SNPs in the remaining sample (2,873 women). Replication was conducted in 1,786 women aged 40 to 70 years old recruited via the Australian Twin Registry, where MD were measured using Cumulus-3.0, assessing 14 SNPs with a p value <0.10 in stage 2. Finally, two genetic variants in high linkage disequilibrium with our best hit were studied using the whole Spanish sample. Evidence of association with MD was found for variant rs11205277 (OR = 0.74; 95% CI = 0.67-0.81; p = 1.33 × 10(-10) ). In replication analysis, only a marginal association between this SNP and absolute dense area was found. There were also evidence of association between MD and SNPs in high linkage disequilibrium with rs11205277, rs11205303 in gene MTMR11 (OR = 0.73; 95% CI = 0.66-0.80; p = 2.64 × 10(-11) ) and rs67807996 in gene OTUD7B (OR = 0.72; 95% CI = 0.66-0.80; p = 2.03 × 10(-11)). Our findings provide additional evidence on common genetic variations that may contribute to MD.

Diet quality and related factors among Spanish female participants in breast cancer screening programs.

OBJECTIVE: A healthy diet is particularly important during menopause, a period in which the risk of a number of health problems increases. This study analyzed diet quality as measured by two indices, namely, the Alternate Healthy Eating Index (AHEI) and the Alternate Mediterranean Diet (aMED) index, which measures adherence to a Mediterranean diet, and examined the factors associated with lower diet quality. METHODS: This was a cross-sectional study covering 3,564 women aged 45 to 68 years who underwent breast cancer screening at 7 centers (Corunna, Barcelona, Burgos, Palma de Mallorca, Pamplona, Valencia, and Zaragoza). Data on diet were collected using a food frequency questionnaire validated for the Spanish population. We calculated the AHEI out of a total of 80 points and the aMED out of a total of 9 points. Ordinal logistic regression models were fitted, taking diet quality (tertiles of the AHEI and the aMED) as dependent variables. The following were included in the final multivariate models as explanatory variables: sociodemographic characteristics, chronic diseases, and lifestyles that were associated with diet quality, with a P value <0.100 in an initial simple model (adjusted solely for calorie intake and screening center). Interaction between menopause status and the other explanatory variables was checked. RESULTS: The median score for AHEI was 40 of a maximum of 80 points. Lower diet quality was registered by the youngest women (P for trend < 0.001), premenopausal and perimenopausal women (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.01-1.56; and OR, 1.48; CI, 1.20-1.83, respectively), obese women (OR, 1.18; CI, 0.99-1.41), those with a diagnosis of diabetes (OR, 1.35; CI, 1.01-1.79), smokers (OR, 1.41; CI, 1.21-1.66), and women reporting lower daily physical activity (OR, 1.31; CI, 1.12-1.53). Better diet quality was shown by women with higher education (OR, 0.74; CI, 0.62-0.88) and ex-smokers (OR, 0.82; CI, 0.69-0.98). Nulliparity was associated with higher AHEI scores, but only among premenopausal women (OR, 0.50; CI, 0.32-0.78). aMED index varied between 0 and 9 (median 5). Lower scores were associated with younger age (P for trend < 0.001), low socioeconomic level (OR, 1.13; CI, 0.96-1.33), lower educational level (P for trend = 0.008), and low level of daily physical activity (OR, 1.27, CI, 1.08-1.50). CONCLUSIONS: The youngest women, the most sedentary women, and those who had a lower educational level and socioeconomic status registered worse diet quality. Ex-smokers and postmenopausal women obtained better scores, probably reflecting a keener concern about leading a healthy life.

Adult weight gain, fat distribution and mammographic density in Spanish pre- and post-menopausal women (DDM-Spain).

High mammographic density (MD) is a phenotype risk marker for breast cancer. Body mass index (BMI) is inversely associated with MD, with the breast being a fat storage site. We investigated the influence of abdominal fat distribution and adult weight gain on MD, taking age, BMI and other confounders into account. Because visceral adiposity and BMI are associated with breast cancer only after menopause, differences in pre- and post-menopausal women were also explored. We recruited 3,584 women aged 45-68 years within the Spanish breast cancer screening network. Demographic, reproductive, family and personal history data were collected by purpose-trained staff, who measured current weight, height, waist and hip circumferences under the same protocol and with the same tools. MD was assessed in the left craniocaudal view using Boyd's Semiquantitative Scale. Association between waist-to-hip ratio, adult weight gain (difference between current weight and self-reported weight at 18 years) and MD was quantified by ordinal logistic regression, with random center-specific intercepts. Models were adjusted for age, BMI, breast size, time since menopause, parity, family history of breast cancer and hormonal replacement therapy use. Natural splines were used to describe the shape of the relationship between these two variables and MD. Waist-to-hip ratio was inversely associated with MD, and the effect was more pronounced in pre-menopausal (OR = 0.53 per 0.1 units; 95 % CI = 0.42-0.66) than in post-menopausal women (OR = 0.73; 95 % CI = 0.65-0.82) (P of heterogeneity = 0.010). In contrast, adult weight gain displayed a positive association with MD, which was similar in both groups (OR = 1.17 per 6 kg; 95 % CI = 1.11-1.23). Women who had gained more than 24 kg displayed higher MD (OR = 2.05; 95 % CI = 1.53-2.73). MD was also evaluated using Wolfe's and Tabár's classifications, with similar results being obtained. Once BMI, fat distribution and other confounders were considered, our results showed a clear dose-response gradient between the number of kg gained during adulthood and the proportion of dense tissue in the breast.

Obstetric history and mammographic density: a population-based cross-sectional study in Spain (DDM-Spain).

High mammographic density (MD) is used as a phenotype risk marker for developing breast cancer. During pregnancy and lactation the breast attains full development, with a cellular-proliferation followed by a lobular-differentiation stage. This study investigates the influence of obstetric factors on MD among pre- and post-menopausal women. We enrolled 3,574 women aged 45-68 years who were participating in breast cancer screening programmes in seven screening centers. To measure MD, blind anonymous readings were taken by an experienced radiologist, using craniocaudal mammography and Boyd's semiquantitative scale. Demographic and reproductive data were directly surveyed by purpose-trained staff at the date of screening. The association between MD and obstetric variables was quantified by ordinal logistic regression, with screening centre introduced as a random effect term. We adjusted for age, number of children and body mass index, and stratified by menopausal status. Parity was inversely associated with density, the probability of having high MD decreased by 16% for each new birth (P value < 0.001). Among parous women, a positive association was detected with duration of lactation [>9 months: odds ratio (OR) = 1.33; 95% confidence interval (CI) = 1.02-1.72] and weight of first child (>3,500 g: OR = 1.32; 95% CI = 1.12-1.54). Age at first birth showed a different effect in pre- and post-menopausal women (P value for interaction = 0.030). No association was found among pre-menopausal women. However, in post-menopausal women the probability of having high MD increased in women who had their first child after the age of 30 (OR = 1.53; 95% CI = 1.17-2.00). A higher risk associated with birth of twins was also mainly observed in post-menopausal women (OR = 2.02; 95% CI = 1.18-3.46). Our study shows a greater prevalence of high MD in mothers of advanced age at first birth, those who had twins, those who have breastfed for longer periods, and mothers whose first child had an elevated birth weight. These results suggest the influence of hormones and growth factors over the proliferative activity of the mammary gland.

Childhood factors associated with mammographic density in adult women.

Growth and development factors could contribute to the development of breast cancer associated with an increase in mammographic density. This study examines the influence of certain childhood-related, socio-demographic and anthropometric variables on mammographic density in adult woman. The study covered 3574 women aged 45-68 years, participating in breast cancer-screening programmes in seven Spanish cities. Based on a craniocaudal mammogram, blind, anonymous measurement of mammographic density was made by a single radiologist, using Boyd's semiquantitative scale. Data associated with the early stages of life were obtained from a direct survey. Ordinal logistic regression and generalised linear models were employed to estimate the association between mammographic density and the variables covered by the questionnaire. Screening programme was introduced as a random effects term. Age, number of children, body mass index (BMI) and other childhood-related variables were used as adjustment variables, and stratified by menopausal status. A total of 811 women (23%) presented mammographic density of over 50%, and 5% of densities exceeded 75%. Our results show a greater prevalence of high mammographic density in women with low prepubertal weight (OR: 1.18; 95% CI: 1.02-1.36); marked prepubertal height (OR: 1.25; 95% CI: 0.97-1.60) and advanced age of their mothers at their birth (>39 years: OR: 1.28; 95% CI: 1.03-1.60); and a lower prevalence of high mammographic density in women with higher prepubertal weight, low birth weight and earlier menarche. The influence of these early-life factors may be explained by greater exposure to hormones and growth factors during the development of the breast gland, when breast tissue would be particularly susceptible to proliferative and carcinogenic stimulus.

Alcohol, tobacco, and mammographic density: a population-based study.

Mammographic density (MD), or the proportion of the breast with respect to its overall area that is composed of dense tissue, is a strong risk factor for breast cancer. Studies support a positive association of mammographic density and alcohol drinking. This was a cross-sectional multicenter study based on 3584 women, aged 45-68 years, recruited from seven screening centers within the Spanish breast cancer screening program network. The association between MD, alcohol consumption and tobacco use was evaluated by using ordinal logistic models with random center-specific intercepts. We found a weak positive association between current alcohol intake and higher MD, with current alcohol consumption increasing the odds of high MD by 13% (OR = 1.13; 95% CI 0.99-1.28) and high daily grams of alcohol being positively associated with increased MD (P for trend = 0.045). There were no statistically significant differences in MD between smokers and non-smokers. Nevertheless, increased number of daily cigarettes and increased number of accumulated lifetime cigarettes were negatively associated with high MD (P for trend 0.017 and 0.021). The effect of alcohol on MD was modified by menopausal status and tobacco smoking: whereas, alcohol consumption and daily grams of alcohol were positively associated with higher MD in postmenopausal women and in women who were not currently smoking, alcohol consumption had no effect on MD in premenopausal women and current smokers. Our results support an association between recent alcohol consumption and high MD, characterized by a modest increase in risk at low levels of current consumption and a decrease in risk among heavier drinkers. Our study also shows how the effects of alcohol in the breast can be modified by other factors, such as smoking.

Validation of obesity based on self-reported data in Spanish women participants in breast cancer screening programmes.

BACKGROUND: Measurement of obesity using self-reported anthropometric data usually involves underestimation of weight and/or overestimation of height. The dual aim of this study was, first, to ascertain and assess the validity of new cut-off points, for both overweight and obesity, using self-reported Body Mass Index furnished by women participants in breast cancer screening programmes, and second, to estimate and validate a predictive model that allows recalculate individual BMI based on self-reported data. METHODS: The study covered 2927 women enrolled at 7 breast cancer screening centres. At each centre, women were randomly selected in 2 samples, in a ratio of 2:1. The larger sample (n = 1951) was used to compare the values of measured and self-reported weight and height, to ascertain new overweight and obesity cut-off points with self-reported data, using ROC curves, and to estimate a predictive model of real BMI using a regression model. The second sample (n = 976) was used to validate the proposed cut-off points and the predictive model. RESULTS: Whereas reported prevalence of obesity was 19.8%, measured prevalence was 28.2%. The sensitivity and specificity of this classification would be maximised if the new cut-off points were 24.30 kg/m2 for overweight and 28.39 kg/m2 for obesity. The probability of classifying women correctly in their real weight categories on the basis of these points was 82.5% in the validation sample. Sensitivity and specificity for determining obesity using the new cut-off point in the validation sample were 90.0% and 92.3% respectively. The predictive model for real BMI included the self-reported BMI, age and educational level (university studies vs lower levels of education). This model succeeded in correctly classifying 90.5% of women according to BMI categories, but its performance was similar to that obtained with the new cut-off points. CONCLUSIONS: Quantification of self-reported obesity entails a considerable underestimation of this problem, thereby questioning its validity. The new cut-off points established in this study and the predictive equation both allow for more accurate estimation of these prevalences.