Residential exposure to traffic pollution and mammographic density in premenopausal women.

BACKGROUND: Mammographic density (MD) is the most important breast cancer biomarker. Ambient pollution is a carcinogen, and its relationship with MD is unclear. This study aims to explore the association between exposure to traffic pollution and MD in premenopausal women. METHODOLOGY: This Spanish cross-sectional study involved 769 women attending gynecological examinations in Madrid. Annual Average Daily Traffic (AADT), extracted from 1944 measurement road points provided by the City Council of Madrid, was weighted by distances (d) between road points and women's addresses to develop a Weighted Traffic Exposure Index (WTEI). Three methods were employed: method-1 (1dAADT), method-2 (1dAADT), and method-3 (e1dAADT). Multiple linear regression models, considering both log-transformed percentage of MD and untransformed MD, were used to estimate MD differences by WTEI quartiles, through two strategies: "exposed (exposure buffers between 50 and 200 m) vs. not exposed (>200 m)"; and "degree of traffic exposure". RESULTS: Results showed no association between MD and traffic pollution according to buffers of exposure to the WTEI (first strategy) for the three methods. The highest reductions in MD, although not statistically significant, were detected in the quartile with the highest traffic exposure. For instance, method-3 revealed a suggestive inverse trend (eßQ1 = 1.23, eßQ2 = 0.96, eßQ3 = 0.85, eßQ4 = 0.85, p-trend = 0.099) in the case of 75 m buffer. Similar non-statistically significant trends were observed with Methods-1 and -2. When we examined the effect of traffic exposure considering all the 1944 measurement road points in every participant (second strategy), results showed no association for any of the three methods. A slightly decreased MD, although not significant, was observed only in the quartile with the highest traffic exposure: eßQ4 = 0.98 (method-1), and eßQ4 = 0.95 (methods-2 and -3). CONCLUSIONS: Our results showed no association between exposure to traffic pollution and MD in premenopausal women. Further research is needed to validate these findings.

Mammographic density in the environs of multiple industrial sources.

BACKGROUND: Mammographic density (MD), defined as the percentage of dense fibroglandular tissue in the breast, is a modifiable marker of the risk of developing breast cancer. Our objective was to evaluate the effect of residential proximity to an increasing number of industrial sources in MD. METHODS: A cross-sectional study was conducted on 1225 premenopausal women participating in the DDM-Madrid study. We calculated distances between women's houses and industries. The association between MD and proximity to an increasing number of industrial facilities and industrial clusters was explored using multiple linear regression models. RESULTS: We found a positive linear trend between MD and proximity to an increasing number of industrial sources for all industries, at distances of 1.5 km (p-trend = 0.055) and 2 km (p-trend = 0.083). Moreover, 62 specific industrial clusters were analyzed, highlighting the significant associations found between MD and proximity to the following 6 industrial clusters: cluster 10 and women living at ≤1.5 km (ß = 10.78, 95 % confidence interval (95%CI) = 1.59; 19.97) and at ≤2 km (ß = 7.96, 95%CI = 0.21; 15.70); cluster 18 and women residing at ≤3 km (ß = 8.48, 95%CI = 0.01; 16.96); cluster 19 and women living at ≤3 km (ß = 15.72, 95%CI = 1.96; 29.49); cluster 20 and women living at ≤3 km (ß = 16.95, 95%CI = 2.90; 31.00); cluster 48 and women residing at ≤3 km (ß = 15.86, 95%CI = 3.95; 27.77); and cluster 52 and women living at ≤2.5 km (ß = 11.09, 95%CI = 0.12; 22.05). These clusters include the following industrial activities: surface treatment of metals/plastic, surface treatment using organic solvents, production/processing of metals, recycling of animal waste, hazardous waste, urban waste-water treatment plants, inorganic chemical industry, cement and lime, galvanization, and food/beverage sector. CONCLUSIONS: Our results suggest that women living in the proximity to an increasing number of industrial sources and those near certain types of industrial clusters have higher MD.

Breast Dense Tissue Segmentation with Noisy Labels: A Hybrid Threshold-Based and Mask-Based Approach.

Breast density assessed from digital mammograms is a known biomarker related to a higher risk of developing breast cancer. Supervised learning algorithms have been implemented to determine this. However, the performance of these algorithms depends on the quality of the ground-truth information, which expert readers usually provide. These expert labels are noisy approximations to the ground truth, as there is both intra- and inter-observer variability among them. Thus, it is crucial to provide a reliable method to measure breast density from mammograms. This paper presents a fully automated method based on deep learning to estimate breast density, including breast detection, pectoral muscle exclusion, and dense tissue segmentation. We propose a novel confusion matrix (CM)-YNet model for the segmentation step. This architecture includes networks to model each radiologist's noisy label and gives the estimated ground-truth segmentation as well as two parameters that allow interaction with a threshold-based labeling tool. A multi-center study involving 1785 women whose "for presentation" mammograms were obtained from 11 different medical facilities was performed. A total of 2496 mammograms were used as the training corpus, and 844 formed the testing corpus. Additionally, we included a totally independent dataset from a different center, composed of 381 women with one image per patient. Each mammogram was labeled independently by two expert radiologists using a threshold-based tool. The implemented CM-Ynet model achieved the highest DICE score averaged over both test datasets (0.82±0.14) when compared to the closest dense-tissue segmentation assessment from both radiologists. The level of concordance between the two radiologists showed a DICE score of 0.76±0.17. An automatic breast density estimator based on deep learning exhibited higher performance when compared with two experienced radiologists. This suggests that modeling each radiologist's label allows for better estimation of the unknown ground-truth segmentation. The advantage of the proposed model is that it also provides the threshold parameters that enable user interaction with a threshold-based tool.

A deep learning framework to classify breast density with noisy labels regularization.

BACKGROUND AND OBJECTIVE: Breast density assessed from digital mammograms is a biomarker for higher risk of developing breast cancer. Experienced radiologists assess breast density using the Breast Image and Data System (BI-RADS) categories. Supervised learning algorithms have been developed with this objective in mind, however, the performance of these algorithms depends on the quality of the ground-truth information which is usually labeled by expert readers. These labels are noisy approximations of the ground truth, as there is often intra- and inter-reader variability among labels. Thus, it is crucial to provide a reliable method to obtain digital mammograms matching BI-RADS categories. This paper presents RegL (Labels Regularizer), a methodology that includes different image pre-processes to allow both a correct breast segmentation and the enhancement of image quality through an intensity adjustment, thus allowing the use of deep learning to classify the mammograms into BI-RADS categories. The Confusion Matrix (CM) - CNN network used implements an architecture that models each radiologist's noisy label. The final methodology pipeline was determined after comparing the performance of image pre-processes combined with different DL architectures. METHODS: A multi-center study composed of 1395 women whose mammograms were classified into the four BI-RADS categories by three experienced radiologists is presented. A total of 892 mammograms were used as the training corpus, 224 formed the validation corpus, and 279 the test corpus. RESULTS: The combination of five networks implementing the RegL methodology achieved the best results among all the models in the test set. The ensemble model obtained an accuracy of (0.85) and a kappa index of 0.71. CONCLUSIONS: The proposed methodology has a similar performance to the experienced radiologists in the classification of digital mammograms into BI-RADS categories. This suggests that the pre-processing steps and modelling of each radiologist's label allows for a better estimation of the unknown ground truth labels.

Residential proximity to industrial pollution and mammographic density.

BACKGROUND: Mammographic density (MD), expressed as percentage of fibroglandular breast tissue, is an important risk factor for breast cancer. Our objective is to investigate the relationship between MD and residential proximity to pollutant industries in premenopausal Spanish women. METHODS: A cross-sectional study was carried out in a sample of 1225 women extracted from the DDM-Madrid study. Multiple linear regression models were used to assess the association of MD percentage (and their 95% confidence intervals (95%CIs)) and proximity (between 1 km and 3 km) to industries included in the European Pollutant Release and Transfer Register. RESULTS: Although no association was found between MD and distance to all industries as a whole, several industrial sectors showed significant association for some distances: "surface treatment of metals and plastic" (ß = 4.98, 95%CI = (0.85; 9.12) at ≤1.5 km, and ß = 3.00, 95%CI = (0.26; 5.73) at ≤2.5 km), "organic chemical industry" (ß = 6.73, 95%CI = (0.50; 12.97) at ≤1.5 km), "pharmaceutical products" (ß = 4.14, 95%CI = (0.58; 7.70) at ≤2 km; ß = 3.55, 95%CI = (0.49; 6.60) at ≤2.5 km; and ß = 3.11, 95%CI = (0.20; 6.01) at ≤3 km), and "urban waste-water treatment plants" (ß = 8.06, 95%CI = (0.82; 15.30) at ≤1 km; ß = 5.28; 95%CI = (0.49; 10.06) at ≤1.5 km; ß = 4.30, 95%CI = (0.03; 8.57) at ≤2 km; ß = 5.26, 95%CI = (1.83; 8.68) at ≤2.5 km; and ß = 3.19, 95%CI = (0.46; 5.92) at ≤3 km). Moreover, significant increased MD was observed in women close to industries releasing specific pollutants: ammonia (ß = 4.55, 95%CI = (0.26; 8.83) at ≤1.5 km; and ß = 3.81, 95%CI = (0.49; 7.14) at ≤2 km), dichloromethane (ß = 3.86, 95%CI = (0.00; 7.71) at ≤2 km), ethylbenzene (ß = 8.96, 95%CI = (0.57; 17.35) at ≤3 km), and phenols (ß = 2.60, 95%CI = (0.21; 5.00) at ≤2.5 km). CONCLUSIONS: Our results suggest no statistically significant relationship between MD and proximity to industries as a whole, although we detected associations with various industrial sectors and some specific pollutants, which suggests that MD could have a mediating role in breast carcinogenesis.

Contest of Best Practices tackling social inequalities in cancer prevention: an iPAAC initiative.

Current health promotion and early cancer detection programmes yield different results depending on the social group and have a different impact among individuals. Thus, they may generate social inequalities in health. The Contest of Best Practices tackling social inequalities in cancer prevention is an initiative that emerged in the framework of the Innovative Partnership for Action Against Cancer Joint Action. This contest identifies interventions that have proven to be effective in reducing social inequalities in cancer prevention in European countries, with the aim of sharing lessons learned and inspiring solutions, as well as facilitating replication in other health systems and similar social settings.

Relationship between the Risk of Gastric Cancer and Adherence to the Mediterranean Diet According to Different Estimators. MCC-Spain Study.

The aim was to assess the effect of adherence to the Mediterranean Diet, measured with five different indexes, on the risk of gastric cancer. Data come from the multicase-control study MCC-Spain, which included 354 gastric cancer cases and 3040 controls with data on diet. We used five indexes to evaluate adherence to the Mediterranean diet and assess the association between each pattern with the risk of gastric cancer, using multivariate logistic regression. The analyses were performed for the whole set of gastric cancer cases, by anatomical location (cardia and non-cardia) and by histological type (intestinal and diffuse). According to the used index, a high adherence protects one from gastric cancer (between 48% (aOR = 0.52; CI 95% = 0.28-0.94) and 75% (aOR = 0.25; CI 95% = 0.12-0.52)), from non-cardia (between 48% (aOR = 0.52; CI 95% = 0.36-0.75) and 65% (aOR = 0.35; CI 95% = 0.23-0.52)), and from the intestinal type (between 41% (aOR = 0.59; CI 95% = 0.36-0.95) and 72% (aOR = 0.28; CI 95% = 0.16-0.50)), but not from the diffuse type. In conclusion, high adherence to a Mediterranean diet pattern is a protective factor for the risk of gastric cancer, with greater adherence leading to greater protection.

[Results of 10 years of the Colorectal Cancer Prevention Program in the Valencian Community.] / Resultados de 10 años del Programa de Prevención de Cáncer Colorrectal en la Comunitat Valenciana.

OBJECTIVE: The population-based Program for the Prevention of Colorectal Cancer (PPCRC) was implemented in 2005 in the Valencian Community, following the guidelines of the European Union. To achieve the desired effectiveness in these programs, it is necessary to achieve a series of requirements, assessable through the program indicators. The objective of this study was to analyze the evolution of the program indicators from 2006 to 2016. METHODS: The accumulated indicators for the period were calculated. The Poisson regression model was used to compare the indicators by age groups and sex, by type of screening, by type of fecal occult blood test (FOBT) and by year. RESULTS: The number of people invited to participate was 1,934,266. The participation rate was 44.4%, being 87.6% in the subsequent screening and 33.7% in the initial one, with men over 60 having the lowest participation figures. Except for the positive predictive value (PPV) for low risk adenomas, which was higher in a group of men aged 50 to 59 years of successive screening, the detection rates and PPV for the different types of lesions were higher in the initial screening, with immunological test and in the group of men over 60 years old. Throughout the period, there was a decrease in the test positivity rates and in the advanced adenomas and cancers detection rates. CONCLUSIONS: The PPCCR reaches levels of quality for which the effectiveness of the program is demonstrated. However, the insufficient participation of some population groups highlights the need to carry out studies to achieve the desired objectives in all population groups and thus result in greater effectiveness of the program.

OBJETIVO: El Programa Poblacional de Preven-ción de Cáncer Colorrectal (PPCCR) se implantó en 2005 en la Comunitat Valenciana, siguiendo las directrices de la Unión Europea. Para alcanzar la efectividad deseada en estos programas es necesario conseguir una serie de requisitos, valorables mediante los indicadores del programa. El objetivo del presente estudio fue analizar la evolución de los indicadores del programa de 2006 a 2016. METODOS: Se calcularon los indicadores acumulados para el periodo. Se empleó el modelo de regresión de Poisson para comparar los indicadores por grupos de edad y sexo, por tipología de cribado, por tipo de test de sangre oculta en heces (TSOH) y por año. RESULTADOS: El número de personas invitadas a participar fue de 1.934.266. La tasa de participación fue del 44,4%, siendo del 87,6% en el cribado sucesivo y del 33,7% en el inicial, teniendo los hombres mayores de 60 años las menores cifras de participación. Excepto el valor predictivo positivo (VPP) para adenomas de bajo riesgo, que fue superior en grupo de hombres de 50 a 59 años en cribado sucesivo, las tasas de detección y VPP para los diferentes tipos de lesiones fueron mayores en el cribado inicial, con el tipo de test inmunológico y en el grupo de hombres mayores de 60 años. A lo largo del periodo se produjo un descenso en las tasas de positividad para el test y las tasas de detección de adenomas avanzados y cánceres. CONCLUSIONES: El PPCCR alcanza niveles de calidad para los que se demuestra la eficacia del programa. Sin embargo, la participación insuficiente de algunos grupos poblacionales remarca la necesidad de realizar estudios para conseguir los objetivos deseados en todos los grupos poblacionales y así redundar en una mayor eficacia del programa.

Occupation, occupational exposures and mammographic density in Spanish women.

INTRODUCTION: Mammographic density (MD), the proportion of radiologically dense breast tissue, is a strong risk factor for breast cancer. Our objective is to investigate the influence of occupations and occupational exposure to physical, chemical, and microbiological agents on MD in Spanish premenopausal women. METHODS: This is a cross-sectional study based on 1362 premenopausal workers, aged 39-50, who attended a gynecological screening in a breast radiodiagnosis unit of Madrid City Council. The work history was compiled through a personal interview. Exposure to occupational agents was evaluated using the Spanish job-exposure matrix MatEmESp. MD percentage was assessed using the validated semi-automated computer tool DM-Scan. The association between occupation, occupational exposures, and MD was quantified using multiple linear regression models, adjusted for age, educational level, body mass index, parity, previous breast biopsies, family history of breast cancer, energy intake, use of oral contraceptives, smoking, and alcohol consumption. RESULTS: Although no occupation was statistically significantly associated with MD, a borderline significant inverse association was mainly observed in orchard, greenhouse, nursery, and garden workers (ß = -6.60; 95% confidence interval (95%CI) = -14.27; 1.07) and information and communication technology technicians (ß = -7.27; 95%CI = -15.37; 0.84). On the contrary, a positive association was found among technicians in art galleries, museums, and libraries (ß = 8.47; 95%CI = -0.65; 17.60). Women occupationally exposed to fungicides, herbicides, and insecticides tended to have lower MD. The percentage of density decreased by almost 2% for every 5 years spent in occupations exposed to the mentioned agents. CONCLUSIONS: Although our findings point to a lack of association with the occupations and exposures analyzed, this study supports a deeper exploration of the role of certain occupational agents in MD, such as pesticides.

[Inequalities in access to cancer screening programmes in Spain and how to reduce them: data from 2013 and 2020.] / Desigualdades de acceso a los programas de cribado del cáncer en España y cómo reducirlas: datos de 2013 y 2020.

OBJECTIVE: The European Commission recommends ensuring equity in cancer screening. The aim of this study was to find out if there were inequalities in access to cancer screening programmes in Spain. METHODS: A transversal study was carried out by means of a survey addressed to the people responsible for breast, colorectal (CRC) and cervical cancer screening programmes in the 19 Autonomous Communities (AC) of Spain in 2013 and 2020. Information was collected on organizational characteristics, inequalities in access and interventions to reduce them. A descriptive analysis was made by AC and time period, by calculating frequencies and percentages, depending on the type of programme (breast, CRC and cervix). RESULTS: In 2013, 14 ACs participated for the breast programme, 8 for the CRC and 7 for the cervical programme; and in 2020, 14, 13 and 11 ACs respectively. All breast programmes were population-based in both periods (14/14 in 2013 and 14/14 in 2020), as well as CRC ones (8/8 in 2013 and 13/13 in 2020), with an increase in cervical cancer programmes (0/7 en 2013 y 6/11 en 2020). In both periods, social groups not included in the target population and groups that were less involved were identified, with differences according to the type of programme. A total of 53 interventions were carried out to reduce inequalities in access (27 in breast, 22 in RCC and 4 in cervical), 66% of them aimed at specific social groups (35/53). CONCLUSIONS: Inequalities in access to cancer screening programmes in Spain are identified, as well as interventions to reduce them.

OBJETIVO: La Comisión Europea recomienda asegurar la equidad en el cribado del cáncer. El objetivo de este estudio fue conocer si existían desigualdades en el acceso a los programas de cribado del cáncer en España. METODOS: Se realizó un estudio transversal mediante encuesta dirigida a las personas responsables de los programas de cribado del cáncer de mama, colorrectal (CCR) y cérvix de las diecinueve Comunidades Autónomas (CCAA) del Estado Español en 2013 y 2020. Se recogió información sobre características organizativas, desigualdades de acceso e intervenciones para reducirlas. Se hizo un análisis descriptivo por CCAA y periodo temporal, mediante el cálculo de frecuencias y porcentajes, en función del tipo de programa (mama, CCR y cérvix). RESULTADOS: En 2013 participaron catorce CCAA para el programa de mama, ocho para el de CCR y siete para el de cérvix, y en 2020, catorce, trece y once CCAA, respectivamente. Todos los programas de mama eran poblacionales en ambos periodos (14/14 en 2013 y 14/14 en 2020), así como los de CCR (8/8 en 2013 y 13/13 en 2020), con un aumento en el caso de los programas de cribado del cáncer de cérvix (0/7 en 2013 y 6/11 en 2020). Se identificaron en ambos periodos grupos sociales no incluidos en la población diana y grupos que, estando incluidos, participaban menos, con diferencias según el tipo de programa. Se realizaron un total de cincuenta y tres intervenciones para reducir desigualdades en el acceso (veintisiete en mama, veintidós en CCR y cuatro en cérvix), el 66% de ellas dirigidas a grupos sociales específicos (35/53). CONCLUSIONES: Se identifican desigualdades de acceso a los programas de cribado del cáncer en España, así como intervenciones para reducirlas.

[Do women in the Valencian Community accept self-sampling as a form of cervical cancer screening?] / ¿Aceptan las mujeres de la Comunidad Valenciana la auto-toma como forma de cribado de cáncer de cérvix?

OBJECTIVE: The use of new devices such as the self-sampling for the determination of the Human Papilloma Virus (HPV), could facilitate the implementation of population screening programs and increase the participation of women. The objective of the study was to find out the women´s knowledge and attitudes towards cervical cancer screening as well as the acceptability of self-sampling. METHODS: Analytical cross-sectional study by telephone survey carried out on a random sample of 389 women from 35 to 65 years of age. The women were asked about their attitudes and knowledge of the screening and preference for HPV determination by self-sampling or by a healthcare professional. RESULTS: 86.9% of the women preferred self-sampling as a screening method and 93.3% had undergone a previous cervical cytology. 51.4% of the women had a high level of knowledge about cervical cancer screening. Younger women (POR 9.26; 95% CI 1.04-24.38), higher level of education (POR 4.6; 95% CI: 1.92-11.00), and higher level of knowledge (POR 2.78; 95% CI: 1.69-9.29), presented higher preferences for the determination of HPV by self-sampling. The trend in age, educational level and knowledge was the same for the prevalence of previous cervical cytology. CONCLUSIONS: The acceptance of self-testing as a method of cervical cancer screening is high among women. Efforts should be made to raise awareness among women to reduce possible inequalities in access and to encourage informed participation.

OBJETIVO: El uso de la auto-toma para determinación del Virus del Papiloma Humano (VPH), podría facilitar la implantación de los programas de cribado poblacional y aumentar la participación de las mujeres. El objetivo de estudio fue conocer los conocimientos y actitudes de las mujeres frente al cribado del cáncer de cérvix y la aceptación de la auto-toma como método de cribado para la detección del VPH. METODOS: Estudio transversal analítico mediante encuesta telefónica realizada a una muestra aleatoria de 389 mujeres entre 35 y 65 años de la Comunitat Valenciana. Se preguntó a las mujeres sobre prácticas preventivas previas, actitudes y conocimientos del cribado, y la preferencia por la determinación de VPH mediante auto-toma o por un profesional sanitario. RESULTADOS: El 86,9% de las mujeres encuestadas prefirieron la auto-toma como método de cribado y el 93,3% se habían realizado una citología cervical previa. El 51,4% de las mujeres tenían un nivel de conocimiento alto sobre el cribado del cáncer de cérvix. Las mujeres de menor edad (POR 9,26; IC95%1,04-24,38), mayor nivel de estudios (POR 4,6; IC95%:1,92-11,00), y mayor nivel de conocimientos (POR 2,78; IC95%:1,69-9,29), presentaron preferencias mayores por la determinación de VPH mediante auto-toma. La tendencia en la edad, nivel de estudios y conocimientos fue la misma para la prevalencia de realización de la citología cervical previa. CONCLUSIONES: La aceptación de la auto-toma como método de cribado del cáncer de cérvix es elevada entre las mujeres. Se deben dedicar esfuerzos para aumentar el conocimiento en las mujeres para reducir posibles desigualdades de acceso y fomentar una participación informada.

A deep learning system to obtain the optimal parameters for a threshold-based breast and dense tissue segmentation.

BACKGROUND AND OBJECTIVE: Breast cancer is the most frequent cancer in women. The Spanish healthcare network established population-based screening programs in all Autonomous Communities, where mammograms of asymptomatic women are taken with early diagnosis purposes. Breast density assessed from digital mammograms is a biomarker known to be related to a higher risk to develop breast cancer.It is thus crucial to provide a reliable method to measure breast density from mammograms. Furthermore the complete automation of this segmentation process is becoming fundamental as the amount of mammograms increases every day. Important challenges are related with the differences in images from different devices and the lack of an objective gold standard.This paper presents a fully automated framework based on deep learning to estimate the breast density. The framework covers breast detection, pectoral muscle exclusion, and fibroglandular tissue segmentation. METHODS: A multi-center study, composed of 1785 women whose "for presentation" mammograms were segmented by two experienced radiologists. A total of 4992 of the 6680 mammograms were used as training corpus and the remaining (1688) formed the test corpus. This paper presents a histogram normalization step that smoothed the difference between acquisition, a regression architecture that learned segmentation parameters as intrinsic image features and a loss function based on the DICE score. RESULTS: The results obtained indicate that the level of concordance (DICE score) reached by the two radiologists (0.77) was also achieved by the automated framework when it was compared to the closest breast segmentation from the radiologists. For the acquired with the highest quality device, the DICE score per acquisition device reached 0.84, while the concordance between radiologists was 0.76. CONCLUSIONS: An automatic breast density estimator based on deep learning exhibits similar performance when compared with two experienced radiologists. It suggests that this system could be used to support radiologists to ease its work.

Serum Phospholipid Fatty Acids and Mammographic Density in Premenopausal Women.

BACKGROUND: The role of fatty acids (FAs) on mammographic density (MD) is unclear, and available studies are based on self-reported dietary intake. OBJECTIVES: This study assessed the association between specific serum phospholipid fatty acids (PLFAs) and MD in premenopausal women. METHODS: The cross-sectional study DDM-Madrid recruited 1392 Spanish premenopausal women, aged 39-50 y, who attended a screening in a breast radiodiagnosis unit of Madrid City Council. Women completed lifestyle questionnaires and FFQs. Percentage MD was estimated using a validated computer tool (DM-Scan), and serum PLFA percentages were measured by GC-MS. Multivariable linear regression models were used to quantify the association of FA tertiles with MD. Models were adjusted for age, education, BMI, waist circumference, parity, oral contraceptive use, previous breast biopsies, and energy intake, and they were corrected for multiple testing. RESULTS: Women in the third tertile of SFAs showed significantly higher MD compared with those in the first tertile (ßT3vsT1 = 7.53; 95% CI: 5.44, 9.61). Elevated relative concentrations of palmitoleic (ßT3vsT1 = 3.12; 95% CI: 0.99, 5.25) and gondoic (ßT3vsT1 = 2.67; 95% CI: 0.57, 4.77) MUFAs, as well as high relative concentrations of palmitelaidic (ßT3vsT1 = 5.22; 95% CI: 3.15, 7.29) and elaidic (ßT3vsT1 = 2.69; 95% CI: 0.59, 4.79) trans FAs, were also associated with higher MD. On the contrary, women with elevated relative concentrations of n-6 (ω-6) linoleic (ßT3vsT1 = -5.49; 95% CI; -7.62, -3.35) and arachidonic (ßT3vsT1 = -4.68; 95% CI: -6.79, -2.58) PUFAs showed lower MD. Regarding desaturation indices, an elevated palmitoleic to palmitic ratio and a low ratio of oleic to steric and arachidonic to dihomo-γ-linolenic acids were associated with higher MD. CONCLUSIONS: Spanish premenopausal women with high relative concentrations of most SFAs and some MUFAs and trans FAs showed an increased MD, whereas those with high relative concentrations of some n-6 PUFAs presented lower density. These results, which should be confirmed in further studies, underscore the importance of analyzing serum FAs individually.

Global parenchymal texture features based on histograms of oriented gradients improve cancer development risk estimation from healthy breasts.

BACKGROUND: The breast dense tissue percentage on digital mammograms is one of the most commonly used markers for breast cancer risk estimation. Geometric features of dense tissue over the breast and the presence of texture structures contained in sliding windows that scan the mammograms may improve the predictive ability when combined with the breast dense tissue percentage. METHODS: A case/control study nested within a screening program covering 1563 women with craniocaudal and mediolateral-oblique mammograms (755 controls and the contralateral breast mammograms at the closest screening visit before cancer diagnostic for 808 cases) aging 45 to 70 from Comunitat Valenciana (Spain) was used to extract geometric and texture features. The dense tissue segmentation was performed using DMScan and validated by two experienced radiologists. A model based on Random Forests was trained several times varying the set of variables. A training dataset of 1172 patients was evaluated with a 10-stratified-fold cross-validation scheme. The area under the Receiver Operating Characteristic curve (AUC) was the metric for the predictive ability. The results were assessed by only considering the output after applying the model to the test set, which was composed of the remaining 391 patients. RESULTS: The AUC score obtained by the dense tissue percentage (0.55) was compared to a machine learning-based classifier results. The classifier, apart from the percentage of dense tissue of both views, firstly included global geometric features such as the distance of dense tissue to the pectoral muscle, dense tissue eccentricity or the dense tissue perimeter, obtaining an accuracy of 0.56. By the inclusion of a global feature based on local histograms of oriented gradients, the accuracy of the classifier was significantly improved (0.61). The number of well-classified patients was improved up to 236 when it was 208. CONCLUSION: Relative geometric features of dense tissue over the breast and histograms of standardized local texture features based on sliding windows scanning the whole breast improve risk prediction beyond the dense tissue percentage adjusted by geometrical variables. Other classifiers could improve the results obtained by the conventional Random Forests used in this study.

Alkylphenolic compounds and risk of breast and prostate cancer in the MCC-Spain study.

BACKGROUND: Alkylphenolic compounds are chemicals with endocrine disrupting properties that have been widely used in industry with important changes in their usage over time. Few epidemiologic studies have evaluated the effect of alkylphenolic compounds on human health. OBJECTIVES: We investigated whether occupational exposure to alkylphenolic compounds is associated with breast and prostate cancer. METHODS: We carried out a population-based case-control study including 1513 incident cases of breast cancer, 1095 of prostate cancer, and 3055 controls, frequency matched by sex, age and region. Occupational exposure to alkylphenolic compounds was estimated using a recently developed job-exposure matrix, which considered different scenarios of exposure and different subtypes of alkylphenolic compounds. RESULTS: History of occupational exposure to alkylphenolic compounds was modestly associated with breast cancer (OR = 1.23; 95% CI = 1.01-1.48). Within the different scenarios, the occupational use of domestic tensioactives was positively associated with breast cancer (OR = 1.28; 95% CI = 1.02-1.60), while occupational exposure in other scenarios showed mostly a suggestion of a similar positive associations. Exposure to nonylphenol ethoxylates was positively associated with breast cancer (OR = 1.21; 95% CI = 1.00-1.47), while exposure to other compounds was uncommon. In general, we did not observe associations between alkylphenolic compounds and prostate cancer, except for a positive association among men occupationally exposed to cosmetic, hair and personal hygiene products. CONCLUSIONS: Our findings suggest a modest association between breast cancer risk and occupational exposure to alkylphenolic compounds, and no associations between these compounds and prostate cancer risk. These findings warrant further corroboration in other studies.

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.

Serum 25-hydroxyvitamin D and breast cancer risk by pathological subtype (MCC-Spain).

Epidemiologic evidence on the association between vitamin D and breast cancer is still inconclusive. This study analyzes the association between serum 25-hydroxyvitamin D (25(OH)D) and breast cancer risk by pathologic subtype, stage at diagnosis and specific breast cancer risk factors. We conducted a population-based multicase-control study where 546 histologically-confirmed breast cancer cases and 558 population controls, frequently matched by geographic area, age and body mass index, were recruited in 12 Spanish provinces (MCC-Spain). Information was collected by a questionnaire and plasma 25(OH)D was measured by solid-phase extraction on-line coupled to liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS). Odds ratios and 95% confidence intervals were calculated using logistic and multinomial mixed regression models. We found a clear protective effect between 25(OH)D levels and breast cancer risk, with a significant dose-response trend (OR per 10 nmol/L = 0.88; 95%CI = 0.82-0.94). While no differences were observed between pre and postmenopausal women, stage at diagnosis, or across strata of the main breast cancer risk factors, the protection was more pronounced for triple negative tumors (OR per 10 nmol/L = 0.64; p-heterogeneity = 0.038). Similar results were observed when only cases sampled in the first month after diagnosis were considered. The protective effect of vitamin D on breast cancer risk may be subtype specific, being stronger for more aggressive tumors, which provides a new approach to prevent this disease.

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.