Differences in breast cancer-risk factors between screen-detected and non-screen-detected cases (MCC-Spain study).

PURPOSE: The variation in breast cancer (BC)-risk factor associations between screen-detected (SD) and non-screen-detected (NSD) tumors has been poorly studied, despite the interest of this aspect in risk assessment and prevention. This study analyzes the differences in breast cancer-risk factor associations according to detection method and tumor phenotype in Spanish women aged between 50 and 69. METHODS: We examined 900 BC cases and 896 controls aged between 50 and 69, recruited in the multicase-control MCC-Spain study. With regard to the cases, 460 were detected by screening mammography, whereas 144 were diagnosed by other means. By tumor phenotype, 591 were HR+, 153 were HER2+, and 58 were TN. Lifestyle, reproductive factors, family history of BC, and tumor characteristics were analyzed. Logistic regression models were used to compare cases vs. controls and SD vs. NSD cases. Multinomial regression models (controls used as a reference) were adjusted for case analysis according to phenotype and detection method. RESULTS: TN was associated with a lower risk of SD BC (OR 0.30 IC 0.10-0.89), as were intermediate (OR 0.18 IC 0.07-0.44) and advanced stages at diagnosis (OR 0.11 IC 0.03-0.34). Nulliparity in postmenopausal women and age at menopause were related to an increased risk of SD BC (OR 1.60 IC 1.08-2.36; OR 1.48 IC 1.09-2.00, respectively). Nulliparity in postmenopausal women was associated with a higher risk of HR+ (OR 1.66 IC 1.15-2.40). Age at menopause was related to a greater risk of HR+ (OR 1.60 IC 1.22-2.11) and HER2+ (OR 1.59 IC 1.03-2.45) tumors. CONCLUSION: Reproductive risk factors are associated with SD BC, as are HR+ tumors. Differences in BC-risk factor associations according to detection method may be related to prevailing phenotypes among categories.

Impact of the COVID-19 pandemic during Spain's state of emergency on the diagnosis of colorectal cancer.

INTRODUCTION: We evaluate the impact of COVID-epidemic in colorectal cancer (CRC) diagnosis during Spain's state of emergency. METHODS: We compared newly diagnosed patients with patients diagnosed in the same period of 2019. RESULTS: A new diagnosis of CRC decreased 48% with a higher rate of patients diagnosed in the emergency setting (12.1% vs. 3.6%; p = .048) and a lower rate diagnosed in the screening program (5.2% vs. 33.3%; p = .000). CONCLUSIONS: Fewer patients have been diagnosed with CRC, with a higher rate of patients diagnosed in an emergency setting.

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.

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.

Mammographic density and risk of breast cancer according to tumor characteristics and mode of detection: a Spanish population-based case-control study.

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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Recalibration of the Gail model for predicting invasive breast cancer risk in Spanish women: a population-based cohort study.

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.

Association of occupational heat exposure and colorectal cancer in the MCC-Spain study.

OBJECTIVE: Heat exposure and heat stress/strain is a concern for many workers. There is increasing interest in potential chronic health effects of occupational heat exposure, including cancer risk. We examined potential associations of occupational heat exposure and colorectal cancer (CRC) risk in a large Spanish multi-case--control study. METHODS: We analyzed data on 1198 histologically confirmed CRC cases and 2690 frequency-matched controls. The Spanish job-exposure matrix, MatEmEsp, was used to assign heat exposure estimates to the lifetime occupations of participants. Three exposure indices were assessed: ever versus never exposed, cumulative exposure and duration (years). We estimated odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression adjusting for potential confounders. RESULTS: Overall, there was no association of ever, compared with never, occupational heat exposure and CRC (OR 1.09, 95% CI 0.92-1.29). There were also no associations observed according to categories of cumulative exposure or duration, and there was no evidence for a trend. There was no clear association of ever occupational heat exposure and CRC in analysis conducted among either men or women when analyzed separately. Positive associations were observed among women in the highest categories of cumulative exposure (OR 1.81, 95% CI 1.09-3.03) and duration (OR 2.89, 95% CI 1.50-5.59) as well as some evidence for a trend (P<0.05). CONCLUSION: Overall, this study provides no clear evidence for an association between occupational heat exposure and CRC.

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.

Impact of intermediate mammography assessment on the likelihood of false-positive results in breast cancer screening programmes.

OBJECTIVES: Breast cancer screening is offered to 100% of the target population in Spain and intermediate mammograms (IMs) are sometimes indicated. This study was aimed at analysing the frequency of IMs, the factors determining their recommendation, and their impact on the risk of false-positive results and the detection rate. METHODS: Data from 3,471,307 mammograms from Spanish breast cancer screening programmes were included. RESULTS: 3.36% of the mammograms were IMs. The factors associated with the use of IMs were age, initial screening, previous invasive tests, a familial history of breast cancer and use of hormone replacement therapy. In screening episodes with an IM, the probability of a false-positive result was 13.74% (95% CI: 13.43-14.05), almost double that in episodes without IMs (6.02%, 95% CI 5.99-6.05). In young women with previous invasive procedures, a familial history of breast cancer or hormone replacement therapy use who were undergoing their initial screen, this probability was lower when IMs were performed. IMs always increased the detection rate. CONCLUSIONS: The factors prompting IMs should be characterised so that radiologists can systematise their recommendations according to the presence of the factors maximising the benefits and minimising the adverse effects of this procedure. KEY POINTS: Intermediate mammograms in breast screening offer potential benefits but also disadvantages. Intermediate mammograms increase the false-positive rate except in specific groups. Intermediate mammograms reduce the false-positive rate in younger women and initial screens. Intermediate mammograms also reduce false-positive results in women with personal risk factors. Intermediate mammograms increase cancer detection mainly in women without risk factors.

Pleomorphic carcinoma of the breast with expression of macrophage markers: report of two cases.

Pleomorphic ductal carcinoma of the breast is a rare variant included in the morphological group of infiltrating ductal carcinoma. The pleomorphic carcinoma is composed predominantly of epithelial and multinucleated tumor giant cells. We report here two cases presenting a lesion composed microscopically of a proliferation of large pleomorphic cells with a predominance of multinucleated giant cells. These lesions were negative for estrogen receptor, progesterone receptor and Her2-neu (triple-negative phenotype). Basal markers (cytokeratin 5/6, cytokeratin 17 and epidermal growth factor receptor [EGFR]) were present, accompanied by the presence of histiocyte marker CD163 in most neoplastic giant cells. High-grade pleomorphic breast carcinomas with the triple-negative phenotype and expression of basal markers might be included in the basal subtype. This is the first report about the co-expression of macrophage marker CD163, with tumor (P53) or epithelial markers (CAM5.2), as indicated by double immunohistochemistry in pleomorphic ductal carcinoma of the breast.

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.

Evaluation of mammographic density patterns: reproducibility and concordance among scales.

BACKGROUND: Increased mammographic breast density is a moderate risk factor for breast cancer. Different scales have been proposed for classifying mammographic density. This study sought to assess intra-rater agreement for the most widely used scales (Wolfe, Tabár, BI-RADS and Boyd) and compare them in terms of classifying mammograms as high- or low-density. METHODS: The study covered 3572 mammograms drawn from women included in the DDM-Spain study, carried-out in seven Spanish Autonomous Regions. Each mammogram was read by an expert radiologist and classified using the Wolfe, Tabár, BI-RADS and Boyd scales. In addition, 375 mammograms randomly selected were read a second time to estimate intra-rater agreement for each scale using the kappa statistic. Owing to the ordinal nature of the scales, weighted kappa was computed. The entire set of mammograms (3572) was used to calculate agreement among the different scales in classifying high/low-density patterns, with the kappa statistic being computed on a pair-wise basis. High density was defined as follows: percentage of dense tissue greater than 50% for the Boyd, "heterogeneously dense and extremely dense" categories for the BI-RADS, categories P2 and DY for the Wolfe, and categories IV and V for the Tabár scales. RESULTS: There was good agreement between the first and second reading, with weighted kappa values of 0.84 for Wolfe, 0.71 for Tabár, 0.90 for BI-RADS, and 0.92 for Boyd scale. Furthermore, there was substantial agreement among the different scales in classifying high- versus low-density patterns. Agreement was almost perfect between the quantitative scales, Boyd and BI-RADS, and good for those based on the observed pattern, i.e., Tabár and Wolfe (kappa 0.81). Agreement was lower when comparing a pattern-based (Wolfe or Tabár) versus a quantitative-based (BI-RADS or Boyd) scale. Moreover, the Wolfe and Tabár scales classified more mammograms in the high-risk group, 46.61 and 37.32% respectively, while this percentage was lower for the quantitative scales (21.89% for BI-RADS and 21.86% for Boyd). CONCLUSIONS: Visual scales of mammographic density show a high reproducibility when appropriate training is provided. Their ability to distinguish between high and low risk render them useful for routine use by breast cancer screening programs. Quantitative-based scales are more specific than pattern-based scales in classifying populations in the high-risk group.

Author Correction: Validating a breast cancer score in Spanish women. The MCC-Spain study.

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

Decline in age at menarche among Spanish women born from 1925 to 1962.

BACKGROUND: While the timing of reproductive events varies across populations, a downward trend in age at menarche has nevertheless been reported in most of the developed world over the past century. Given the impact of change in age at menarche on health conditions, this study sought to examine secular trends in age at menarche among women living in Navarre (Northern Spain) who participated in a population-based breast cancer screening programme. METHODS: The study was based on 110545 women born from 1925 to 1962. Trends were tested using a linear regression model, in which year of birth was entered continuously as the predictor and age at menarche (years) as the response variable, using size of town and region of birth as covariates. RESULTS: Among women born in Navarre between 1925 and 1962, age at menarche declined steadily from an average of 13.72 years in the 1925-1929 birth-cohorts to 12.83 years in the 1958-1962 birth-cohorts. Controlling for size of town or city of birth, age at menarche declined by an average of 0.132 years every 5 years over the period 1925-1962. This decline was greater in women born in rural versus urban settings. Trends were also different among regions of birth. CONCLUSION: We report a population-based study showing a downward trend in age of onset of menarche among Spanish women born in the period 1925-1962, something that is more pronounced among women born in rural settings and varies geographically.

Dietary Inflammatory Index, Dietary Non-Enzymatic Antioxidant Capacity, and Colorectal and Breast Cancer Risk (MCC-Spain Study).

Inflammation and antioxidant capacity have been associated with colorectal and breast cancer. We computed the dietary inflammatory index (DII®), and the total dietary non-enzymatic antioxidant capacity (NEAC) and associated them with colorectal and breast cancer risk in the population-based multi case-control study in Spain (MCC-Spain). We included 1852 colorectal cancer and 1567 breast cancer cases, and 3447 and 1486 population controls, respectively. DII score and NEAC were derived using data from a semi-quantitative validated food frequency questionnaire. Unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95%CI) for energy-adjusted DII (E-DII), and a score combining E-DII and NEAC. E-DII was associated with colorectal cancer risk (OR = 1.93, highest quartile versus lowest, 95%CI:1.60-2.32; p-trend: <0.001); this increase was observed for both colon and rectal cancer. Less pronounced increased risks were observed for breast cancer (OR = 1.22, highest quartile versus lowest, 95%CI:0.99-1.52, p-trend: >0.10). The combined score of high E-DII scores and low antioxidant values were associated with colorectal cancer risk (OR = 1.48, highest quartile versus lowest, 95%CI: 1.26-1.74; p-trend: <0.001), but not breast cancer. This study provides evidence that a pro-inflammatory diet is associated with increased colorectal cancer risk while findings for breast cancer were less consistent.

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.

Validating a breast cancer score in Spanish women. The MCC-Spain study.

A breast-risk score, published in 2016, was developed in white-American women using 92 genetic variants (GRS92), modifiable and non-modifiable risk factors. With the aim of validating the score in the Spanish population, 1,732 breast cancer cases and 1,910 controls were studied. The GRS92, modifiable and non-modifiable risk factor scores were estimated via logistic regression. SNPs without available genotyping were simulated as in the aforementioned 2016 study. The full model score was obtained by combining GRS92, modifiable and non-modifiable risk factor scores. Score performances were tested via the area under the ROC curve (AUROC), net reclassification index (NRI) and integrated discrimination improvement (IDI). Compared with non-modifiable and modifiable factor scores, GRS92 had higher discrimination power (AUROC: 0.6195, 0.5885 and 0.5214, respectively). Adding the non-modifiable factor score to GRS92 improved patient classification by 23.6% (NRI = 0.236), while the modifiable factor score only improved it by 7.2%. The full model AUROC reached 0.6244. A simulation study showed the ability of the full model for identifying women at high risk for breast cancer. In conclusion, a model combining genetic and risk factors can be used for stratifying women by their breast cancer risk, which can be applied to individualizing genetic counseling and screening recommendations.

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.