Survival of Breast Cancer by Stage, Grade and Molecular Groups in Mallorca, Spain.

The aims of this study are: (1) to determine cause-specific survival by stage, grade, and molecular groups of breast cancer, (2) to identify factors which explain and predict the likelihood of survival and the risk of dying from this cancer; and (3) to find out the distribution of breast cancer cases by stage, grade, and molecular groups in females diagnosed in the period 2006-2012 in Mallorca (Spain). We collected data regarding age, date and diagnostic method, histology, laterality, sublocation, pathological or clinical tumor size (T), pathological or clinical regional lymph nodes (N), metastasis (M) and stage, histologic grade, estrogen and progesterone receptors status, HER-2 expression, Ki67 level, molecular classification, date of last follow-up or date of death, and cause of death. We identified 2869 cases. Cause-specific survival for the entire sample was 96% 1 year after diagnosis, 91% at 3 years and 87% at 5 years. Relative survival was 96.9% 1 year after diagnosis, 92.6% at 3 years and 88.5% at 5 years. The competing-risks regression model determined that patients over 65 years of age and patients with triple negative cancer have worse prognoses, and as stages progress, the prognosis for breast cancer worsens, especially from stage III.

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.

Barriers to and discourses about breast cancer prevention among immigrant women in Spain: a qualitative study.

OBJECTIVES: To identify knowledge, barriers and discourses about breast cancer screening in Spain among female immigrants from low-income countries and native Spanish women from a low socioeconomic class. DESIGN: Qualitative interview study with thematic analysis interpreted using cultural mediators. SETTING: Mallorca, Spain. PARTICIPANTS: Thirty-six in-depth interviews, using cultural mediators, of immigrant women living in Mallorca who were 50-69 years old and were from Maghreb, Sub-Saharan Africa, Eastern Europe, Latin America, China or were native to Spain and from a low socioeconomic class. RESULTS: We analysed the interviews to assess breast cancer perceptions and beliefs, discourses about breast cancer prevention and barriers to accessing breast cancer prevention programmes. Although the women reported an association of breast cancer with death, they acknowledged the effectiveness of early detection. They also exhibited reluctance to talk about cancer. Discourses about cancer prevention tended to be proactive or fatalistic, depending on the woman's country of origin. For all women, fear of results and lack of time were barriers that limited participation in breast cancer prevention programmes. Language barriers, frequent changes of residence and fear due to status as an irregular (undocumented) immigrant were barriers specific to immigrant women. CONCLUSIONS: The culture of origin affects whether an immigrant has a fatalistic or proactive approach toward breast cancer screening. Immigrants from low-income countries and Spanish natives from a low socioeconomic class experience barriers in access to breast cancer screening. Frequently changing homes is also a barrier for immigrant women.

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.

Use of hormone therapy and isoflavones and mammographic density in Spain.

OBJECTIVE: The use of some forms of hormone therapy (HT) is associated with an increase in mammographic density-a major risk factor for breast cancer. The role of isoflavones, however, is unclear. Here, we quantify the prevalence of HT and isoflavone use among postmenopausal Spanish women, determine associated risk factors, and explore the relationship between these therapies and mammographic density. METHODS: This cross-sectional study included 2,754 postmenopausal women who underwent breast cancer screening in seven geographical areas. Mammographic density was evaluated using Boyd's semiquantitative scale. Multinomial logistic regression models were adjusted to assess risk factors associated with both therapies. Ordinal regression models were fitted to study the association between HT and isoflavone consumption with mammographic density. RESULTS: The prevalence of ever-use of HT was 12%, whereas that of the current use was 2.3%. Isoflavone lifetime prevalence was 3.7%, and current use was 1.7%. The most common HT types were tibolone and estrogens. Surgical menopause, oral contraceptive use, educational level, population density, and years since menopause were positively associated with HT, whereas body mass index and parity were inversely associated. Mammographic density was not associated with current or past HT use. However, women who reported having consumed isoflavones in the past and those who started their use after menopause had a higher mammographic density when compared with never-users (odds ratio 1.98, 95% CI 1.21-3.25, P = 0.007; and odds ratio 1.60, 95% CI 1.01-2.53, P = 0.045 respectively). CONCLUSIONS: Our results show a low prevalence of HT and isoflavone use in postmenopausal Spanish women. In this population, HT use was not associated with mammographic density, whereas some categories of isoflavone users had higher density.

Association between the Adherence to the International Guidelines for Cancer Prevention and Mammographic Density.

INTRODUCTION: Mammographic density (MD) is considered a strong predictor of Breast Cancer (BC). The objective of the present study is to explore the association between MD and the compliance with the World Cancer Research Fund and the American Institute for Cancer Research (WCRF/AICR) recommendations for cancer prevention. METHODS: Data of 3584 women attending screening from a population-based multicenter cross-sectional study (DDM-Spain) collected from October 7, 2007 through July 14, 2008, was used to calculate a score that measures the level of compliance with the WCRF/AICR recommendations: R1)Maintain adequate body weight; R2)Be physically active; 3R)Limit the intake of high density foods; R4)Eat mostly plant foods; R5)Limit the intake of animal foods; R6)Limit alcohol intake; R7)Limit salt and salt preserved food intake; R8)Meet nutritional needs through diet. The association between the score and MD (assessed by a single radiologist using a semi-quantitative scale) was evaluated using ordinal logistic models with random center-specific intercepts adjusted for the main determinants of MD. Stratified analyses by menopausal status and smoking status were also carried out. RESULTS: A higher compliance with the WCRF/AICR recommendations was associated with lower MD (OR1-unit increase = 0.93 95%CI:0.86;0.99). The association was stronger in postmenopausal women (OR = 0.91 95%CI:0.84;0.99) and nonsmokers (OR = 0.87;95%CI:0.80;0.96 for nonsmokers, OR = 1.01 95%CI:0.91;1.12 for smokers, P-interaction = 0.042). Among nonsmokers, maintaining adequate body weight (OR = 0.81 95%CI:0.65;1.01), practicing physical activity (OR = 0.68 95%CI:0.48;0.96) and moderating the intake of high-density foods (OR = 0.58 95%CI:0.40;0.86) and alcoholic beverages (OR = 0.76 95%CI:0.55;1.05) were the recommendations showing the strongest associations with MD. CONCLUSIONS: postmenopausal women and non-smokers with greater compliance with the WCRF/AICR guidelines have lower MD. These results may provide guidance to design specific recommendations for screening attendants with high MD and therefore at higher risk of developing BC.

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.

Calorie intake, olive oil consumption and mammographic density among Spanish women.

High mammographic density (MD) is one of the main risk factors for development of breast cancer. To date, however, relatively few studies have evaluated the association between MD and diet. In this cross-sectional study, we assessed the association between MD (measured using Boyd's semiquantitative scale with five categories: <10%, 10-25%, 25-50%, 50-75% and >75%) and diet (measured using a food frequency questionnaire validated in a Spanish population) among 3,548 peri- and postmenopausal women drawn from seven breast cancer screening programs in Spain. Multivariate ordinal logistic regression models, adjusted for age, body mass index (BMI), energy intake and protein consumption as well as other confounders, showed an association between greater calorie intake and greater MD [odds ratio (OR) = 1.23; 95% confidence interval (CI) = 1.10-1.38, for every increase of 500 cal/day], yet high consumption of olive oil was nevertheless found to reduce the prevalence of high MD (OR = 0.86;95% CI = 0.76-0.96, for every increase of 22 g/day in olive oil consumption); and, while greater intake of whole milk was likewise associated with higher MD (OR = 1.10; 95%CI 1.00-1.20, for every increase of 200 g/day), higher consumption of protein (OR = 0.89; 95% CI 0.80-1.00, for every increase of 30 g/day) and white meat (p for trend 0.041) was found to be inversely associated with MD. Our study, the largest to date to assess the association between diet and MD, suggests that MD is associated with modifiable dietary factors, such as calorie intake and olive oil consumption. These foods could thus modulate the prevalence of high MD, and important risk marker for breast cancer.

Validation of DM-Scan, a computer-assisted tool to assess mammographic density in full-field digital mammograms.

We developed a semi-automated tool to assess mammographic density (MD), a phenotype risk marker for breast cancer (BC), in full-field digital images and evaluated its performance testing its reproducibility, comparing our MD estimates with those obtained by visual inspection and using Cumulus, verifying their association with factors that influence MD, and studying the association between MD measures and subsequent BC risk. Three radiologists assessed MD using DM-Scan, the new tool, on 655 processed images (craniocaudal view) obtained in two screening centers. Reproducibility was explored computing pair-wise concordance correlation coefficients (CCC). The agreement between DM-Scan estimates and visual assessment (semi-quantitative scale, 6 categories) was quantified computing weighted kappa statistics (quadratic weights). DM-Scan and Cumulus readings were compared using CCC. Variation of DM-Scan measures by age, body mass index (BMI) and other MD modifiers was tested in regression mixed models with mammographic device as a random-effect term. The association between DM-Scan measures and subsequent BC was estimated in a case-control study. All BC cases in screening attendants (2007-2010) at a center with full-field digital mammography were matched by age and screening year with healthy controls (127 pairs). DM-Scan was used to blindly assess MD in available mammograms (112 cases/119 controls). Unconditional logistic models were fitted, including age, menopausal status and BMI as confounders. DM-Scan estimates were very reliable (pairwise CCC: 0.921, 0.928 and 0.916). They showed a reasonable agreement with visual MD assessment (weighted kappa ranging 0.79-0.81). DM-Scan and Cumulus measures were highly concordant (CCC ranging 0.80-0.84), but ours tended to be higher (4%-5% on average). As expected, DM-Scan estimates varied with age, BMI, parity and family history of BC. Finally, DM-Scan measures were significantly associated with BC (p-trend=0.005). Taking MD<7% as reference, OR per categories of MD were: OR7%-17%=1.32 (95% CI=0.59-2.99), OR17%-28%=2.28 (95% CI=1.03-5.04) and OR>=29%=3.10 (95% CI=1.35-7.14). Our results confirm that DM-Scan is a reliable tool to assess MD in full-field digital mammograms.

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.

Women's features and inter-/intra-rater agreement on mammographic density assessment in full-field digital mammograms (DDM-SPAIN).

Measurement of mammographic density (MD), one of the leading risk factors for breast cancer, still relies on subjective assessment. However, the consistency of MD measurement in full-digital mammograms has yet to be evaluated. We studied inter- and intra-rater agreement with respect to estimation of breast density in full-digital mammograms, and tested whether any of the women's characteristics might have some influence on them. After an initial training period, three experienced radiologists estimated MD using Boyd scale in a left breast cranio-caudal mammogram of 1,431 women, recruited at three Spanish screening centres. A subgroup of 50 randomly selected images was read twice to estimate short-term intra-rater agreement. In addition, a reading of 1,428 of the images, performed 2 years before by one rater, was used to estimate long-term intra-rater agreement. Pair-wise weighted kappas with 95% bootstrap confidence intervals were calculated. Dichotomous variables were defined to identify mammograms in which any rater disagreed with other raters or with his/her own assessment, respectively. The association between disagreement and women's characteristics was tested using multivariate mixed logistic models, including centre as a random-effects term, and taking into account repeated measures when required. All quadratic-weighted kappa values for inter- and intra-rater agreement were excellent (higher than 0.80). None of the studied women's features, i.e. body mass index, brassiere size, menopause, nulliparity, lactation or current hormonal therapy, was associated with higher risk of inter- or intra-rater disagreement. However, raters differed significantly more in images that were classified in the higher-density MD categories, and disagreement in intra-rater assessment was also lower in low-density mammograms. The reliability of MD assessment in full-field digital mammograms is comparable to that for original or digitised images. The reassuring lack of association between subjects' MD-related characteristics and agreement suggests that bias from this source is unlikely.